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• How to Write a Discussion Section | Tips & Examples

How to Write a Discussion Section | Tips & Examples

Published on August 21, 2022 by Shona McCombes . Revised on July 18, 2023.

The discussion section is where you delve into the meaning, importance, and relevance of your results .

It should focus on explaining and evaluating what you found, showing how it relates to your literature review and paper or dissertation topic , and making an argument in support of your overall conclusion. It should not be a second results section.

There are different ways to write this section, but you can focus your writing around these key elements:

• Summary : A brief recap of your key results
• Interpretations: What do your results mean?
• Implications: Why do your results matter?
• Limitations: What can’t your results tell us?
• Recommendations: Avenues for further studies or analyses

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Table of contents

What not to include in your discussion section, step 1: summarize your key findings, step 2: give your interpretations, step 3: discuss the implications, step 4: acknowledge the limitations, step 5: share your recommendations, discussion section example, other interesting articles, frequently asked questions about discussion sections.

There are a few common mistakes to avoid when writing the discussion section of your paper.

• Don’t introduce new results: You should only discuss the data that you have already reported in your results section .
• Don’t make inflated claims: Avoid overinterpretation and speculation that isn’t directly supported by your data.
• Don’t undermine your research: The discussion of limitations should aim to strengthen your credibility, not emphasize weaknesses or failures.

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Start this section by reiterating your research problem and concisely summarizing your major findings. To speed up the process you can use a summarizer to quickly get an overview of all important findings. Don’t just repeat all the data you have already reported—aim for a clear statement of the overall result that directly answers your main research question . This should be no more than one paragraph.

Many students struggle with the differences between a discussion section and a results section . The crux of the matter is that your results sections should present your results, and your discussion section should subjectively evaluate them. Try not to blend elements of these two sections, in order to keep your paper sharp.

• The results indicate that…
• The study demonstrates a correlation between…
• This analysis supports the theory that…
• The data suggest that…

The meaning of your results may seem obvious to you, but it’s important to spell out their significance for your reader, showing exactly how they answer your research question.

The form of your interpretations will depend on the type of research, but some typical approaches to interpreting the data include:

• Identifying correlations , patterns, and relationships among the data
• Discussing whether the results met your expectations or supported your hypotheses
• Contextualizing your findings within previous research and theory
• Explaining unexpected results and evaluating their significance
• Considering possible alternative explanations and making an argument for your position

You can organize your discussion around key themes, hypotheses, or research questions, following the same structure as your results section. Alternatively, you can also begin by highlighting the most significant or unexpected results.

• In line with the hypothesis…
• Contrary to the hypothesized association…
• The results contradict the claims of Smith (2022) that…
• The results might suggest that x . However, based on the findings of similar studies, a more plausible explanation is y .

As well as giving your own interpretations, make sure to relate your results back to the scholarly work that you surveyed in the literature review . The discussion should show how your findings fit with existing knowledge, what new insights they contribute, and what consequences they have for theory or practice.

Ask yourself these questions:

• Do your results support or challenge existing theories? If they support existing theories, what new information do they contribute? If they challenge existing theories, why do you think that is?
• Are there any practical implications?

Your overall aim is to show the reader exactly what your research has contributed, and why they should care.

• These results build on existing evidence of…
• The results do not fit with the theory that…
• The experiment provides a new insight into the relationship between…
• These results should be taken into account when considering how to…
• The data contribute a clearer understanding of…
• While previous research has focused on  x , these results demonstrate that y .

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Even the best research has its limitations. Acknowledging these is important to demonstrate your credibility. Limitations aren’t about listing your errors, but about providing an accurate picture of what can and cannot be concluded from your study.

Limitations might be due to your overall research design, specific methodological choices , or unanticipated obstacles that emerged during your research process.

Here are a few common possibilities:

• If your sample size was small or limited to a specific group of people, explain how generalizability is limited.
• If you encountered problems when gathering or analyzing data, explain how these influenced the results.
• If there are potential confounding variables that you were unable to control, acknowledge the effect these may have had.

After noting the limitations, you can reiterate why the results are nonetheless valid for the purpose of answering your research question.

• The generalizability of the results is limited by…
• The reliability of these data is impacted by…
• Due to the lack of data on x , the results cannot confirm…
• The methodological choices were constrained by…
• It is beyond the scope of this study to…

Based on the discussion of your results, you can make recommendations for practical implementation or further research. Sometimes, the recommendations are saved for the conclusion .

Suggestions for further research can lead directly from the limitations. Don’t just state that more studies should be done—give concrete ideas for how future work can build on areas that your own research was unable to address.

• Further research is needed to establish…
• Future studies should take into account…
• Avenues for future research include…

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In the discussion , you explore the meaning and relevance of your research results , explaining how they fit with existing research and theory. Discuss:

• Your  interpretations : what do the results tell us?
• The  implications : why do the results matter?
• The  limitation s : what can’t the results tell us?

The results chapter or section simply and objectively reports what you found, without speculating on why you found these results. The discussion interprets the meaning of the results, puts them in context, and explains why they matter.

In qualitative research , results and discussion are sometimes combined. But in quantitative research , it’s considered important to separate the objective results from your interpretation of them.

In a thesis or dissertation, the discussion is an in-depth exploration of the results, going into detail about the meaning of your findings and citing relevant sources to put them in context.

The conclusion is more shorter and more general: it concisely answers your main research question and makes recommendations based on your overall findings.

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• How to Write Discussions and Conclusions

The discussion section contains the results and outcomes of a study. An effective discussion informs readers what can be learned from your experiment and provides context for the results.

What makes an effective discussion?

When you’re ready to write your discussion, you’ve already introduced the purpose of your study and provided an in-depth description of the methodology. The discussion informs readers about the larger implications of your study based on the results. Highlighting these implications while not overstating the findings can be challenging, especially when you’re submitting to a journal that selects articles based on novelty or potential impact. Regardless of what journal you are submitting to, the discussion section always serves the same purpose: concluding what your study results actually mean.

A successful discussion section puts your findings in context. It should include:

• the results of your research,
• a discussion of related research, and
• a comparison between your results and initial hypothesis.

Tip: Not all journals share the same naming conventions.

You can apply the advice in this article to the conclusion, results or discussion sections of your manuscript.

Our Early Career Researcher community tells us that the conclusion is often considered the most difficult aspect of a manuscript to write. To help, this guide provides questions to ask yourself, a basic structure to model your discussion off of and examples from published manuscripts. 

Questions to ask yourself:

• Was my hypothesis correct?
• If my hypothesis is partially correct or entirely different, what can be learned from the results? 
• How do the conclusions reshape or add onto the existing knowledge in the field? What does previous research say about the topic? 
• Why are the results important or relevant to your audience? Do they add further evidence to a scientific consensus or disprove prior studies? 
• How can future research build on these observations? What are the key experiments that must be done? 
• What is the “take-home” message you want your reader to leave with?

How to structure a discussion

Trying to fit a complete discussion into a single paragraph can add unnecessary stress to the writing process. If possible, you’ll want to give yourself two or three paragraphs to give the reader a comprehensive understanding of your study as a whole. Here’s one way to structure an effective discussion:

Writing Tips

While the above sections can help you brainstorm and structure your discussion, there are many common mistakes that writers revert to when having difficulties with their paper. Writing a discussion can be a delicate balance between summarizing your results, providing proper context for your research and avoiding introducing new information. Remember that your paper should be both confident and honest about the results! 

• Read the journal’s guidelines on the discussion and conclusion sections. If possible, learn about the guidelines before writing the discussion to ensure you’re writing to meet their expectations. 
• Begin with a clear statement of the principal findings. This will reinforce the main take-away for the reader and set up the rest of the discussion. 
• Explain why the outcomes of your study are important to the reader. Discuss the implications of your findings realistically based on previous literature, highlighting both the strengths and limitations of the research. 
• State whether the results prove or disprove your hypothesis. If your hypothesis was disproved, what might be the reasons? 
• Introduce new or expanded ways to think about the research question. Indicate what next steps can be taken to further pursue any unresolved questions. 
• If dealing with a contemporary or ongoing problem, such as climate change, discuss possible consequences if the problem is avoided. 
• Be concise. Adding unnecessary detail can distract from the main findings. 

Don’t

• Rewrite your abstract. Statements with “we investigated” or “we studied” generally do not belong in the discussion. 
• Include new arguments or evidence not previously discussed. Necessary information and evidence should be introduced in the main body of the paper. 
• Apologize. Even if your research contains significant limitations, don’t undermine your authority by including statements that doubt your methodology or execution. 
• Shy away from speaking on limitations or negative results. Including limitations and negative results will give readers a complete understanding of the presented research. Potential limitations include sources of potential bias, threats to internal or external validity, barriers to implementing an intervention and other issues inherent to the study design. 
• Overstate the importance of your findings. Making grand statements about how a study will fully resolve large questions can lead readers to doubt the success of the research. 

Snippets of Effective Discussions:

Consumer-based actions to reduce plastic pollution in rivers: A multi-criteria decision analysis approach

Identifying reliable indicators of fitness in polar bears

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How to Write a Term Paper From Start to Finish

The term paper, often regarded as the culmination of a semester's hard work, is a rite of passage for students in pursuit of higher education. Here's an interesting fact to kick things off: Did you know that the term paper's origins can be traced back to ancient Greece, where scholars like Plato and Aristotle utilized written works to explore and document their philosophical musings? Just as these great minds once wrote their thoughts on parchment, you, too, can embark on this intellectual voyage with confidence and skill.

How to Write a Term Paper: Short Description

In this article, we'll delve into the core purpose of this kind of assignment – to showcase your understanding of a subject, your research abilities, and your capacity to communicate complex ideas effectively. But it doesn't stop there. We'll also guide you in the art of creating a well-structured term paper format, a roadmap that will not only keep you on track but also ensure your ideas flow seamlessly and logically. Packed with valuable tips on writing, organization, and time management, this resource promises to equip you with the tools needed to excel in your academic writing.

Understanding What Is a Term Paper

A term paper, a crucial component of your college education, is often assigned towards the conclusion of a semester. It's a vehicle through which educators gauge your comprehension of the course content. Imagine it as a bridge between what you've learned in class and your ability to apply that knowledge to real-world topics.

For instance, in a history course, you might be asked to delve into the causes and consequences of a significant historical event, such as World War II. In a psychology class, your term paper might explore the effects of stress on mental health, or in an environmental science course, you could analyze the impact of climate change on a specific region.

Writing a term paper isn't just about summarizing facts. It requires a blend of organization, deep research, and the art of presenting your findings in a way that's both clear and analytical. This means structuring your arguments logically, citing relevant sources, and critically evaluating the information you've gathered.

For further guidance, we've prepared an insightful guide for you authored by our expert essay writer . It's brimming with practical tips and valuable insights to help you stand out in this academic endeavor and earn the recognition you deserve.

How to Start a Term Paper

Before you start, keep the guidelines for the term paper format firmly in mind. If you have any doubts, don't hesitate to reach out to your instructor for clarification before you begin your research and writing process. And remember, procrastination is your worst enemy in this endeavor. If you're aiming to produce an exceptional piece and secure a top grade, it's essential to plan ahead and allocate dedicated time each day to work on it. Now, let our term paper writing services provide you with some valuable tips to help you on your journey:

• Hone Your Topic : Start by cultivating a learning mindset that empowers you to effectively organize your thoughts. Discover how to research a topic in the section below.
• Hook Your Readers: Initiate a brainstorming session and unleash a barrage of creative ideas to captivate your audience right from the outset. Pose intriguing questions, share compelling anecdotes, offer persuasive statistics, and more.
• Craft a Concise Thesis Statement Example : If you find yourself struggling to encapsulate the main idea of your paper in just a sentence or two, it's time to revisit your initial topic and consider narrowing it down.
• Understand Style Requirements: Your work must adhere to specific formatting guidelines. Delve into details about the APA format and other pertinent regulations in the section provided.
• Delve Deeper with Research : Equipped with a clearer understanding of your objectives, dive into your subject matter with a discerning eye. Ensure that you draw from reputable and reliable sources.
• Begin Writing: Don't obsess over perfection from the get-go. Just start writing, and don't worry about initial imperfections. You can always revise or remove those early sentences later. The key is to initiate the term papers as soon as you've amassed sufficient information.

Ace your term paper with EssayPro 's expert help. Our academic professionals are here to guide you through every step, ensuring your term paper is well-researched, structured, and written to the highest standards.

Term Paper Topics

Selecting the right topic for your term paper is a critical step, one that can significantly impact your overall experience and the quality of your work. While instructors sometimes provide specific topics, there are instances when you have the freedom to choose your own. To guide you on how to write a term paper, consider the following factors when deciding on your dissertation topics :

• Relevance to Assignment Length: Begin by considering the required length of your paper. Whether it's a substantial 10-page paper or a more concise 5-page one, understanding the word count will help you determine the appropriate scope for your subject. This will inform whether your topic should be broad or more narrowly focused.
• Availability of Resources : Investigate the resources at your disposal. Check your school or community library for books and materials that can support your research. Additionally, explore online sources to ensure you have access to a variety of reference materials.
• Complexity and Clarity : Ensure you can effectively explain your chosen topic, regardless of how complex it may seem. If you encounter areas that are challenging to grasp fully, don't hesitate to seek guidance from experts or your professor. Clarity and understanding are key to producing a well-structured term paper.
• Avoiding Overused Concepts : Refrain from choosing overly trendy or overused topics. Mainstream subjects often fail to captivate the interest of your readers or instructors, as they can lead to repetitive content. Instead, opt for a unique angle or approach that adds depth to your paper.
• Manageability and Passion : While passion can drive your choice of topic, it's important to ensure that it is manageable within the given time frame and with the available resources. If necessary, consider scaling down a topic that remains intriguing and motivating to you, ensuring it aligns with your course objectives and personal interests.

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Term Paper Outline

Before embarking on the journey of writing a term paper, it's crucial to establish a well-structured outline. Be mindful of any specific formatting requirements your teacher may have in mind, as these will guide your outline's structure. Here's a basic format to help you get started:

• Cover Page: Begin with a cover page featuring your name, course number, teacher's name, and the deadline date, centered at the top.
• Abstract: Craft a concise summary of your work that informs readers about your paper's topic, its significance, and the key points you'll explore.
• Introduction: Commence your term paper introduction with a clear and compelling statement of your chosen topic. Explain why it's relevant and outline your approach to addressing it.
• Body: This section serves as the meat of academic papers, where you present the primary findings from your research. Provide detailed information about the topic to enhance the reader's understanding. Ensure you incorporate various viewpoints on the issue and conduct a thorough analysis of your research.
• Results: Share the insights and conclusions that your research has led you to. Discuss any shifts in your perspective or understanding that have occurred during the course of your project.
• Discussion: Conclude your term paper with a comprehensive summary of the topic and your findings. You can wrap up with a thought-provoking question or encourage readers to explore the subject further through their own research.

How to Write a Term Paper with 5 Steps

Before you begin your term paper, it's crucial to understand what a term paper proposal entails. This proposal serves as your way to introduce and justify your chosen topic to your instructor, and it must gain approval before you start writing the actual paper.

In your proposal, include recent studies or research related to your topic, along with proper references. Clearly explain the topic's relevance to your course, outline your objectives, and organize your ideas effectively. This helps your instructor grasp your term paper's direction. If needed, you can also seek assistance from our expert writers and buy term paper .

Draft the Abstract

The abstract is a critical element while writing a term paper, and it plays a crucial role in piquing the reader's interest. To create a captivating abstract, consider these key points from our dissertation writing service :

• Conciseness: Keep it short and to the point, around 150-250 words. No need for lengthy explanations.
• Highlight Key Elements: Summarize the problem you're addressing, your research methods, and primary findings or conclusions. For instance, if your paper discusses the impact of social media on mental health, mention your research methods and significant findings.
• Engagement: Make your abstract engaging. Use language that draws readers in. For example, if your paper explores the effects of artificial intelligence on the job market, you might begin with a question like, 'Is AI revolutionizing our work landscape, or should we prepare for the robots to take over?'
• Clarity: Avoid excessive jargon or technical terms to ensure accessibility to a wider audience.

Craft the Introduction

The introduction sets the stage for your entire term paper and should engage readers from the outset. To craft an intriguing introduction, consider these tips:

• Hook Your Audience: Start with a captivating hook, such as a thought-provoking question or a compelling statistic. For example, if your paper explores the impact of smartphone addiction, you could begin with, 'Can you remember the last time you went a whole day without checking your phone?'
• State Your Purpose: Clearly state the purpose of your paper and its relevance. If your term paper is about renewable energy's role in combating climate change, explain why this topic is essential in today's world.
• Provide a Roadmap: Briefly outline how your paper is structured. For instance, if your paper discusses the benefits of mindfulness meditation, mention that you will explore its effects on stress reduction, emotional well-being, and cognitive performance.
• Thesis Statement: Conclude your introduction with a concise thesis statement that encapsulates the central argument or message of your paper. In the case of a term paper on the impact of online education, your thesis might be: 'Online education is revolutionizing learning by providing accessibility, flexibility, and innovative teaching methods.'

Develop the Body Sections: Brainstorming Concepts and Content

Generate ideas and compose text: body sections.

The body of your term paper is where you present your research, arguments, and analysis. To generate ideas and write engaging text in the body sections, consider these strategies from our research paper writer :

• Structure Your Ideas: Organize your paper into sections or paragraphs, each addressing a specific aspect of your topic. For example, if your term paper explores the impact of social media on interpersonal relationships, you might have sections on communication patterns, privacy concerns, and emotional well-being.
• Support with Evidence: Back up your arguments with credible evidence, such as data, research findings, or expert opinions. For instance, when discussing the effects of social media on mental health, you can include statistics on social media usage and its correlation with anxiety or depression.
• Offer Diverse Perspectives: Acknowledge and explore various viewpoints on the topic. When writing about the pros and cons of genetic engineering, present both the potential benefits, like disease prevention, and the ethical concerns associated with altering human genetics.
• Use Engaging Examples: Incorporate real-life examples to illustrate your points. If your paper discusses the consequences of climate change, share specific instances of extreme weather events or environmental degradation to make the topic relatable.
• Ask Thought-Provoking Questions: Integrate questions throughout your text to engage readers and stimulate critical thinking. In a term paper on the future of artificial intelligence, you might ask, 'How will AI impact job markets and the concept of work in the coming years?'

Formulate the Conclusion

The conclusion section should provide a satisfying wrap-up of your arguments and insights. To craft a compelling term paper example conclusion, follow these steps:

• Revisit Your Thesis: Begin by restating your thesis statement. This reinforces the central message of your paper. For example, if your thesis is about the importance of biodiversity conservation, reiterate that biodiversity is crucial for ecological balance and human well-being.
• Summarize Key Points: Briefly recap the main points you've discussed in the body of your paper. For instance, if you've been exploring the impact of globalization on local economies, summarize the effects on industries, job markets, and cultural diversity.
• Emphasize Your Main Argument: Reaffirm the significance of your thesis and the overall message of your paper. Discuss why your findings are important or relevant in a broader context. If your term paper discusses the advantages of renewable energy, underscore its potential to combat climate change and reduce our reliance on fossil fuels.
• Offer a Thoughtful Reflection: Share your own reflections or insights about the topic. How has your understanding evolved during your research? Have you uncovered any unexpected findings or implications? If your paper discusses the future of space exploration, consider what it means for humanity's quest to explore the cosmos.
• End with Impact: Conclude your term paper with a powerful closing statement. You can leave the reader with a thought-provoking question, a call to action, or a reflection on the broader implications of your topic. For instance, if your paper is about the ethics of artificial intelligence, you could finish by asking, 'As AI continues to advance, what ethical considerations will guide our choices and decisions?'

Edit and Enhance the Initial Draft

After completing your initial draft, the revision and polishing phase is essential for improving your paper. Here's how to refine your work efficiently:

• Take a Break: Step back and return to your paper with a fresh perspective.
• Structure Check: Ensure your paper flows logically and transitions smoothly from the introduction to the conclusion.
• Clarity and Conciseness: Trim excess words for clarity and precision.
• Grammar and Style: Proofread for errors and ensure consistent style.
• Citations and References: Double-check your citations and reference list.
• Peer Review: Seek feedback from peers or professors for valuable insights.
• Enhance Intro and Conclusion: Make your introduction and conclusion engaging and impactful.
• Coherence Check: Ensure your arguments support your thesis consistently.
• Read Aloud: Reading your paper aloud helps identify issues.
• Final Proofread: Perform a thorough proofread to catch any remaining errors.

Term Paper Format

When formatting your term paper, consider its length and the required citation style, which depends on your research topic. Proper referencing is crucial to avoid plagiarism in academic writing. Common citation styles include APA and MLA.

If unsure how to cite term paper for social sciences, use the APA format, including the author's name, book title, publication year, publisher, and location when citing a book.

For liberal arts and humanities, MLA is common, requiring the publication name, date, and location for referencing.

Adhering to the appropriate term paper format and citation style ensures an organized and academically sound paper. Follow your instructor's guidelines for a polished and successful paper.

Term Paper Example

To access our term paper example, simply click the button below.

The timeline of events from 1776 to 1861, that, in the end, prompted the American Civil War, describes and relates to a number of subjects modern historians acknowledge as the origins and causes of the Civil War. In fact, pre-Civil War events had both long-term and short-term influences on the War—such as the election of Abraham Lincoln as the American president in 1860 that led to the Fall of Fort Sumter in April of the same year. In that period, contentions that surrounded states’ rights progressively exploded in Congress—since they were the initial events that formed after independence. Congress focused on resolving significant issues that affected the states, which led to further issues. In that order, the US’s history from 1776 to 1861 provides a rich history, as politicians brought forth dissimilarities, dissections, and tensions between the Southern US & the people of slave states, and the Northern states that were loyal to the Union. The events that unfolded from the period of 1776 to 1861 involved a series of issues because they promoted the great sectional crisis that led to political divisions and the build-up to the Civil War that made the North and the South seem like distinctive and timeless regions that predated the crisis itself.

Final Thoughts

In closing, approach the task of writing term papers with determination and a positive outlook. Begin well in advance, maintain organization, and have faith in your capabilities. Don't hesitate to seek assistance if required, and express your individual perspective with confidence. You're more than capable of succeeding in this endeavor!

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What is the Difference between a Term Paper and a Research Paper?

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The purpose of the discussion section is to interpret and describe the significance of your findings in relation to what was already known about the research problem being investigated and to explain any new understanding or insights that emerged as a result of your research. The discussion will always connect to the introduction by way of the research questions or hypotheses you posed and the literature you reviewed, but the discussion does not simply repeat or rearrange the first parts of your paper; the discussion clearly explains how your study advanced the reader's understanding of the research problem from where you left them at the end of your review of prior research.

Annesley, Thomas M. “The Discussion Section: Your Closing Argument.” Clinical Chemistry 56 (November 2010): 1671-1674; Peacock, Matthew. “Communicative Moves in the Discussion Section of Research Articles.” System 30 (December 2002): 479-497.

Importance of a Good Discussion

The discussion section is often considered the most important part of your research paper because it:

• Most effectively demonstrates your ability as a researcher to think critically about an issue, to develop creative solutions to problems based upon a logical synthesis of the findings, and to formulate a deeper, more profound understanding of the research problem under investigation;
• Presents the underlying meaning of your research, notes possible implications in other areas of study, and explores possible improvements that can be made in order to further develop the concerns of your research;
• Highlights the importance of your study and how it can contribute to understanding the research problem within the field of study;
• Presents how the findings from your study revealed and helped fill gaps in the literature that had not been previously exposed or adequately described; and,
• Engages the reader in thinking critically about issues based on an evidence-based interpretation of findings; it is not governed strictly by objective reporting of information.

Annesley Thomas M. “The Discussion Section: Your Closing Argument.” Clinical Chemistry 56 (November 2010): 1671-1674; Bitchener, John and Helen Basturkmen. “Perceptions of the Difficulties of Postgraduate L2 Thesis Students Writing the Discussion Section.” Journal of English for Academic Purposes 5 (January 2006): 4-18; Kretchmer, Paul. Fourteen Steps to Writing an Effective Discussion Section. San Francisco Edit, 2003-2008.

Structure and Writing Style

I.  General Rules

These are the general rules you should adopt when composing your discussion of the results :

• Do not be verbose or repetitive; be concise and make your points clearly
• Avoid the use of jargon or undefined technical language
• Follow a logical stream of thought; in general, interpret and discuss the significance of your findings in the same sequence you described them in your results section [a notable exception is to begin by highlighting an unexpected result or a finding that can grab the reader's attention]
• Use the present verb tense, especially for established facts; however, refer to specific works or prior studies in the past tense
• If needed, use subheadings to help organize your discussion or to categorize your interpretations into themes

II.  The Content

The content of the discussion section of your paper most often includes :

• Explanation of results : Comment on whether or not the results were expected for each set of findings; go into greater depth to explain findings that were unexpected or especially profound. If appropriate, note any unusual or unanticipated patterns or trends that emerged from your results and explain their meaning in relation to the research problem.
• References to previous research : Either compare your results with the findings from other studies or use the studies to support a claim. This can include re-visiting key sources already cited in your literature review section, or, save them to cite later in the discussion section if they are more important to compare with your results instead of being a part of the general literature review of prior research used to provide context and background information. Note that you can make this decision to highlight specific studies after you have begun writing the discussion section.
• Deduction : A claim for how the results can be applied more generally. For example, describing lessons learned, proposing recommendations that can help improve a situation, or highlighting best practices.
• Hypothesis : A more general claim or possible conclusion arising from the results [which may be proved or disproved in subsequent research]. This can be framed as new research questions that emerged as a consequence of your analysis.

III.  Organization and Structure

Keep the following sequential points in mind as you organize and write the discussion section of your paper:

• Think of your discussion as an inverted pyramid. Organize the discussion from the general to the specific, linking your findings to the literature, then to theory, then to practice [if appropriate].
• Use the same key terms, narrative style, and verb tense [present] that you used when describing the research problem in your introduction.
• Begin by briefly re-stating the research problem you were investigating and answer all of the research questions underpinning the problem that you posed in the introduction.
• Describe the patterns, principles, and relationships shown by each major findings and place them in proper perspective. The sequence of this information is important; first state the answer, then the relevant results, then cite the work of others. If appropriate, refer the reader to a figure or table to help enhance the interpretation of the data [either within the text or as an appendix].
• Regardless of where it's mentioned, a good discussion section includes analysis of any unexpected findings. This part of the discussion should begin with a description of the unanticipated finding, followed by a brief interpretation as to why you believe it appeared and, if necessary, its possible significance in relation to the overall study. If more than one unexpected finding emerged during the study, describe each of them in the order they appeared as you gathered or analyzed the data. As noted, the exception to discussing findings in the same order you described them in the results section would be to begin by highlighting the implications of a particularly unexpected or significant finding that emerged from the study, followed by a discussion of the remaining findings.
• Before concluding the discussion, identify potential limitations and weaknesses if you do not plan to do so in the conclusion of the paper. Comment on their relative importance in relation to your overall interpretation of the results and, if necessary, note how they may affect the validity of your findings. Avoid using an apologetic tone; however, be honest and self-critical [e.g., in retrospect, had you included a particular question in a survey instrument, additional data could have been revealed].
• The discussion section should end with a concise summary of the principal implications of the findings regardless of their significance. Give a brief explanation about why you believe the findings and conclusions of your study are important and how they support broader knowledge or understanding of the research problem. This can be followed by any recommendations for further research. However, do not offer recommendations which could have been easily addressed within the study. This would demonstrate to the reader that you have inadequately examined and interpreted the data.

IV.  Overall Objectives

The objectives of your discussion section should include the following: I.  Reiterate the Research Problem/State the Major Findings

Briefly reiterate the research problem or problems you are investigating and the methods you used to investigate them, then move quickly to describe the major findings of the study. You should write a direct, declarative, and succinct proclamation of the study results, usually in one paragraph.

II.  Explain the Meaning of the Findings and Why They are Important

No one has thought as long and hard about your study as you have. Systematically explain the underlying meaning of your findings and state why you believe they are significant. After reading the discussion section, you want the reader to think critically about the results and why they are important. You don’t want to force the reader to go through the paper multiple times to figure out what it all means. If applicable, begin this part of the section by repeating what you consider to be your most significant or unanticipated finding first, then systematically review each finding. Otherwise, follow the general order you reported the findings presented in the results section.

III.  Relate the Findings to Similar Studies

No study in the social sciences is so novel or possesses such a restricted focus that it has absolutely no relation to previously published research. The discussion section should relate your results to those found in other studies, particularly if questions raised from prior studies served as the motivation for your research. This is important because comparing and contrasting the findings of other studies helps to support the overall importance of your results and it highlights how and in what ways your study differs from other research about the topic. Note that any significant or unanticipated finding is often because there was no prior research to indicate the finding could occur. If there is prior research to indicate this, you need to explain why it was significant or unanticipated. IV.  Consider Alternative Explanations of the Findings

It is important to remember that the purpose of research in the social sciences is to discover and not to prove . When writing the discussion section, you should carefully consider all possible explanations for the study results, rather than just those that fit your hypothesis or prior assumptions and biases. This is especially important when describing the discovery of significant or unanticipated findings.

V.  Acknowledge the Study’s Limitations

It is far better for you to identify and acknowledge your study’s limitations than to have them pointed out by your professor! Note any unanswered questions or issues your study could not address and describe the generalizability of your results to other situations. If a limitation is applicable to the method chosen to gather information, then describe in detail the problems you encountered and why. VI.  Make Suggestions for Further Research

You may choose to conclude the discussion section by making suggestions for further research [as opposed to offering suggestions in the conclusion of your paper]. Although your study can offer important insights about the research problem, this is where you can address other questions related to the problem that remain unanswered or highlight hidden issues that were revealed as a result of conducting your research. You should frame your suggestions by linking the need for further research to the limitations of your study [e.g., in future studies, the survey instrument should include more questions that ask..."] or linking to critical issues revealed from the data that were not considered initially in your research.

NOTE: Besides the literature review section, the preponderance of references to sources is usually found in the discussion section . A few historical references may be helpful for perspective, but most of the references should be relatively recent and included to aid in the interpretation of your results, to support the significance of a finding, and/or to place a finding within a particular context. If a study that you cited does not support your findings, don't ignore it--clearly explain why your research findings differ from theirs.

V.  Problems to Avoid

• Do not waste time restating your results . Should you need to remind the reader of a finding to be discussed, use "bridge sentences" that relate the result to the interpretation. An example would be: “In the case of determining available housing to single women with children in rural areas of Texas, the findings suggest that access to good schools is important...," then move on to further explaining this finding and its implications.
• As noted, recommendations for further research can be included in either the discussion or conclusion of your paper, but do not repeat your recommendations in the both sections. Think about the overall narrative flow of your paper to determine where best to locate this information. However, if your findings raise a lot of new questions or issues, consider including suggestions for further research in the discussion section.
• Do not introduce new results in the discussion section. Be wary of mistaking the reiteration of a specific finding for an interpretation because it may confuse the reader. The description of findings [results section] and the interpretation of their significance [discussion section] should be distinct parts of your paper. If you choose to combine the results section and the discussion section into a single narrative, you must be clear in how you report the information discovered and your own interpretation of each finding. This approach is not recommended if you lack experience writing college-level research papers.
• Use of the first person pronoun is generally acceptable. Using first person singular pronouns can help emphasize a point or illustrate a contrasting finding. However, keep in mind that too much use of the first person can actually distract the reader from the main points [i.e., I know you're telling me this--just tell me!].

Analyzing vs. Summarizing. Department of English Writing Guide. George Mason University; Discussion. The Structure, Format, Content, and Style of a Journal-Style Scientific Paper. Department of Biology. Bates College; Hess, Dean R. "How to Write an Effective Discussion." Respiratory Care 49 (October 2004); Kretchmer, Paul. Fourteen Steps to Writing to Writing an Effective Discussion Section. San Francisco Edit, 2003-2008; The Lab Report. University College Writing Centre. University of Toronto; Sauaia, A. et al. "The Anatomy of an Article: The Discussion Section: "How Does the Article I Read Today Change What I Will Recommend to my Patients Tomorrow?” The Journal of Trauma and Acute Care Surgery 74 (June 2013): 1599-1602; Research Limitations & Future Research . Lund Research Ltd., 2012; Summary: Using it Wisely. The Writing Center. University of North Carolina; Schafer, Mickey S. Writing the Discussion. Writing in Psychology course syllabus. University of Florida; Yellin, Linda L. A Sociology Writer's Guide . Boston, MA: Allyn and Bacon, 2009.

Writing Tip

Don’t Over-Interpret the Results!

Interpretation is a subjective exercise. As such, you should always approach the selection and interpretation of your findings introspectively and to think critically about the possibility of judgmental biases unintentionally entering into discussions about the significance of your work. With this in mind, be careful that you do not read more into the findings than can be supported by the evidence you have gathered. Remember that the data are the data: nothing more, nothing less.

MacCoun, Robert J. "Biases in the Interpretation and Use of Research Results." Annual Review of Psychology 49 (February 1998): 259-287; Ward, Paulet al, editors. The Oxford Handbook of Expertise . Oxford, UK: Oxford University Press, 2018.

Another Writing Tip

Don't Write Two Results Sections!

One of the most common mistakes that you can make when discussing the results of your study is to present a superficial interpretation of the findings that more or less re-states the results section of your paper. Obviously, you must refer to your results when discussing them, but focus on the interpretation of those results and their significance in relation to the research problem, not the data itself.

Azar, Beth. "Discussing Your Findings."  American Psychological Association gradPSYCH Magazine (January 2006).

Yet Another Writing Tip

Avoid Unwarranted Speculation!

The discussion section should remain focused on the findings of your study. For example, if the purpose of your research was to measure the impact of foreign aid on increasing access to education among disadvantaged children in Bangladesh, it would not be appropriate to speculate about how your findings might apply to populations in other countries without drawing from existing studies to support your claim or if analysis of other countries was not a part of your original research design. If you feel compelled to speculate, do so in the form of describing possible implications or explaining possible impacts. Be certain that you clearly identify your comments as speculation or as a suggestion for where further research is needed. Sometimes your professor will encourage you to expand your discussion of the results in this way, while others don’t care what your opinion is beyond your effort to interpret the data in relation to the research problem.

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Everything You Need to Know to Write an A+ Term Paper

Last Updated: March 4, 2024 Fact Checked

Sample Term Papers

Researching & outlining.

• Drafting Your Paper
• Revising Your Paper

Expert Q&A

This article was co-authored by Matthew Snipp, PhD and by wikiHow staff writer, Raven Minyard, BA . C. Matthew Snipp is the Burnet C. and Mildred Finley Wohlford Professor of Humanities and Sciences in the Department of Sociology at Stanford University. He is also the Director for the Institute for Research in the Social Science’s Secure Data Center. He has been a Research Fellow at the U.S. Bureau of the Census and a Fellow at the Center for Advanced Study in the Behavioral Sciences. He has published 3 books and over 70 articles and book chapters on demography, economic development, poverty and unemployment. He is also currently serving on the National Institute of Child Health and Development’s Population Science Subcommittee. He holds a Ph.D. in Sociology from the University of Wisconsin—Madison. There are 13 references cited in this article, which can be found at the bottom of the page. This article has been fact-checked, ensuring the accuracy of any cited facts and confirming the authority of its sources. This article has been viewed 2,225,015 times.

A term paper is a written assignment given to students at the end of a course to gauge their understanding of the material. Term papers typically count for a good percentage of your overall grade, so of course, you’ll want to write the best paper possible. Luckily, we’ve got you covered. In this article, we’ll teach you everything you need to know to write an A+ term paper, from researching and outlining to drafting and revising.

Quick Steps to Write a Term Paper

• Hook your readers with an interesting and informative intro paragraph. State your thesis and your main points.
• Support your thesis by providing quotes and evidence that back your claim in your body paragraphs.
• Summarize your main points and leave your readers with a thought-provoking question in your conclusion.

• Think of your term paper as the bridge between what you’ve learned in class and how you apply that knowledge to real-world topics.
• For example, a history term paper may require you to explore the consequences of a significant historical event, like the Civil War. An environmental science class, on the other hand, may have you examine the effects of climate change on a certain region.
• Your guidelines should tell you the paper’s word count and formatting style, like whether to use in-text citations or footnotes and whether to use single- or double-spacing. If these things aren’t specified, be sure to reach out to your instructor.

• Make sure your topic isn’t too broad. For example, if you want to write about Shakespeare’s work, first narrow it down to a specific play, like Macbeth , then choose something even more specific like Lady Macbeth’s role in the plot.
• If the topic is already chosen for you, explore unique angles that can set your content and information apart from the more obvious approaches many others will probably take. [3] X Research source
• Try not to have a specific outcome in mind, as this will close you off to new ideas and avenues of thinking. Rather than trying to mold your research to fit your desired outcome, allow the outcome to reflect a genuine analysis of the discoveries you made. Ask yourself questions throughout the process and be open to having your beliefs challenged.
• Reading other people's comments, opinions, and entries on a topic can often help you to refine your own, especially where they comment that "further research" is required or where they posit challenging questions but leave them unanswered.

• For example, if you’re writing a term paper about Macbeth , your primary source would be the play itself. Then, look for other research papers and analyses written by academics and scholars to understand how they interpret the text.

• For example, if you’re writing a paper about Lady Macbeth, your thesis could be something like “Shakespeare’s characterization of Lady Macbeth reveals how desire for power can control someone’s life.”
• Remember, your research and thesis development doesn’t stop here. As you continue working through both the research and writing, you may want to make changes that align with the ideas forming in your mind and the discoveries you continue to unearth.
• On the other hand, don’t keep looking for new ideas and angles for fear of feeling confined. At some point, you’re going to have to say enough is enough and make your point. You may have other opportunities to explore these questions in future studies, but for now, remember your term paper has a finite word length and an approaching due date!

• Abstract: An abstract is a concise summary of your paper that informs readers of your topic, its significance, and the key points you’ll explore. It must stand on its own and make sense without referencing outside sources or your actual paper.
• Introduction: The introduction establishes the main idea of your paper and directly states the thesis. Begin your introduction with an attention-grabbing sentence to intrigue your readers, and provide any necessary background information to establish your paper’s purpose and direction.
• Body paragraphs: Each body paragraph focuses on a different argument supporting your thesis. List specific evidence from your sources to back up your arguments. Provide detailed information about your topic to enhance your readers’ understanding. In your outline, write down the main ideas for each body paragraph and any outstanding questions or points you’re not yet sure about.
• Results: Depending on the type of term paper you’re writing, your results may be incorporated into your body paragraphs or conclusion. These are the insights that your research led you to. Here you can discuss how your perspective and understanding of your topic shifted throughout your writing process.
• Conclusion: Your conclusion summarizes your argument and findings. You may restate your thesis and major points as you wrap up your paper.

Drafting Your Term Paper

• Writing an introduction can be challenging, but don’t get too caught up on it. As you write the rest of your paper, your arguments might change and develop, so you’ll likely need to rewrite your intro at the end, anyway. Writing your intro is simply a means of getting started and you can always revise it later. [10] X Trustworthy Source PubMed Central Journal archive from the U.S. National Institutes of Health Go to source
• Be sure to define any words your readers might not understand. For example, words like “globalization” have many different meanings depending on context, and it’s important to state which ones you’ll be using as part of your introductory paragraph.

• Try to relate the subject of the essay (say, Plato’s Symposium ) to a tangentially related issue you happen to know something about (say, the growing trend of free-wheeling hookups in frat parties). Slowly bring the paragraph around to your actual subject and make a few generalizations about why this aspect of the book/subject is so fascinating and worthy of study (such as how different the expectations for physical intimacy were then compared to now).

• You can also reflect on your own experience of researching and writing your term paper. Discuss how your understanding of your topic evolved and any unexpected findings you came across.

• While peppering quotes throughout your text is a good way to help make your point, don’t overdo it. If you use too many quotes, you’re basically allowing other authors to make the point and write the paper for you. When you do use a quote, be sure to explain why it is relevant in your own words.
• Try to sort out your bibliography at the beginning of your writing process to avoid having a last-minute scramble. When you have all the information beforehand (like the source’s title, author, publication date, etc.), it’s easier to plug them into the correct format.

Revising & Finalizing Your Term Paper

• Trade in weak “to-be” verbs for stronger “action” verbs. For example: “I was writing my term paper” becomes “I wrote my term paper.”

• It’s extremely important to proofread your term paper. If your writing is full of mistakes, your instructor will assume you didn’t put much effort into your paper. If you have too many errors, your message will be lost in the confusion of trying to understand what you’ve written.

• If you add or change information to make things clearer for your readers, it’s a good idea to look over your paper one more time to catch any new typos that may have come up in the process.

• The best essays are like grass court tennis—the argument should flow in a "rally" style, building persuasively to the conclusion. Thanks Helpful 0 Not Helpful 0
• If you get stuck, consider giving your professor a visit. Whether you're still struggling for a thesis or you want to go over your conclusion, most instructors are delighted to help and they'll remember your initiative when grading time rolls around. Thanks Helpful 0 Not Helpful 0
• At least 2 hours for 3-5 pages.
• At least 4 hours for 8-10 pages.
• At least 6 hours for 12-15 pages.
• Double those hours if you haven't done any homework and you haven't attended class.
• For papers that are primarily research-based, add about two hours to those times (although you'll need to know how to research quickly and effectively, beyond the purview of this brief guide).

You Might Also Like

• ↑ https://www.binghamton.edu/counseling/self-help/term-paper.html
• ↑ Matthew Snipp, PhD. Research Fellow, U.S. Bureau of the Census. Expert Interview. 26 March 2020.
• ↑ https://emory.libanswers.com/faq/44525
• ↑ https://writing.wisc.edu/handbook/assignments/planresearchpaper/
• ↑ https://owl.purdue.edu/owl/general_writing/the_writing_process/thesis_statement_tips.html
• ↑ https://libguides.usc.edu/writingguide/outline
• ↑ https://gallaudet.edu/student-success/tutorial-center/english-center/writing/guide-to-writing-introductions-and-conclusions/
• ↑ https://www.ncbi.nlm.nih.gov/pubmed/26731827
• ↑ https://writing.wisc.edu/handbook/assignments/writing-an-abstract-for-your-research-paper/
• ↑ https://www.ivcc.edu/stylesite/Essay_Title.pdf
• ↑ https://www.uni-flensburg.de/fileadmin/content/institute/anglistik/dokumente/downloads/how-to-write-a-term-paper-daewes.pdf
• ↑ https://library.sacredheart.edu/c.php?g=29803&p=185937
• ↑ https://www.cornerstone.edu/blog-post/six-steps-to-really-edit-your-paper/

About This Article

If you need to write a term paper, choose your topic, then start researching that topic. Use your research to craft a thesis statement which states the main idea of your paper, then organize all of your facts into an outline that supports your thesis. Once you start writing, state your thesis in the first paragraph, then use the body of the paper to present the points that support your argument. End the paper with a strong conclusion that restates your thesis. For tips on improving your term paper through active voice, read on! Did this summary help you? Yes No

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How to Write the Discussion Section of a Research Paper

The discussion section of a research paper analyzes and interprets the findings, provides context, compares them with previous studies, identifies limitations, and suggests future research directions.

Updated on September 15, 2023

Structure your discussion section right, and you’ll be cited more often while doing a greater service to the scientific community. So, what actually goes into the discussion section? And how do you write it?

The discussion section of your research paper is where you let the reader know how your study is positioned in the literature, what to take away from your paper, and how your work helps them. It can also include your conclusions and suggestions for future studies.

First, we’ll define all the parts of your discussion paper, and then look into how to write a strong, effective discussion section for your paper or manuscript.

Discussion section: what is it, what it does

The discussion section comes later in your paper, following the introduction, methods, and results. The discussion sets up your study’s conclusions. Its main goals are to present, interpret, and provide a context for your results.

What is it?

The discussion section provides an analysis and interpretation of the findings, compares them with previous studies, identifies limitations, and suggests future directions for research.

This section combines information from the preceding parts of your paper into a coherent story. By this point, the reader already knows why you did your study (introduction), how you did it (methods), and what happened (results). In the discussion, you’ll help the reader connect the ideas from these sections.

Why is it necessary?

The discussion provides context and interpretations for the results. It also answers the questions posed in the introduction. While the results section describes your findings, the discussion explains what they say. This is also where you can describe the impact or implications of your research.

Adds context for your results

Most research studies aim to answer a question, replicate a finding, or address limitations in the literature. These goals are first described in the introduction. However, in the discussion section, the author can refer back to them to explain how the study's objective was achieved. 

Shows what your results actually mean and real-world implications

The discussion can also describe the effect of your findings on research or practice. How are your results significant for readers, other researchers, or policymakers?

What to include in your discussion (in the correct order)

A complete and effective discussion section should at least touch on the points described below.

Summary of key findings

The discussion should begin with a brief factual summary of the results. Concisely overview the main results you obtained.

Begin with key findings with supporting evidence

Your results section described a list of findings, but what message do they send when you look at them all together?

Your findings were detailed in the results section, so there’s no need to repeat them here, but do provide at least a few highlights. This will help refresh the reader’s memory and help them focus on the big picture.

Read the first paragraph of the discussion section in this article (PDF) for an example of how to start this part of your paper. Notice how the authors break down their results and follow each description sentence with an explanation of why each finding is relevant. 

State clearly and concisely

Following a clear and direct writing style is especially important in the discussion section. After all, this is where you will make some of the most impactful points in your paper. While the results section often contains technical vocabulary, such as statistical terms, the discussion section lets you describe your findings more clearly. 

Interpretation of results

Once you’ve given your reader an overview of your results, you need to interpret those results. In other words, what do your results mean? Discuss the findings’ implications and significance in relation to your research question or hypothesis.

Analyze and interpret your findings

Look into your findings and explore what’s behind them or what may have caused them. If your introduction cited theories or studies that could explain your findings, use these sources as a basis to discuss your results.

For example, look at the second paragraph in the discussion section of this article on waggling honey bees. Here, the authors explore their results based on information from the literature.

Unexpected or contradictory results

Sometimes, your findings are not what you expect. Here’s where you describe this and try to find a reason for it. Could it be because of the method you used? Does it have something to do with the variables analyzed? Comparing your methods with those of other similar studies can help with this task.

Context and comparison with previous work

Refer to related studies to place your research in a larger context and the literature. Compare and contrast your findings with existing literature, highlighting similarities, differences, and/or contradictions.

How your work compares or contrasts with previous work

Studies with similar findings to yours can be cited to show the strength of your findings. Information from these studies can also be used to help explain your results. Differences between your findings and others in the literature can also be discussed here. 

How to divide this section into subsections

If you have more than one objective in your study or many key findings, you can dedicate a separate section to each of these. Here’s an example of this approach. You can see that the discussion section is divided into topics and even has a separate heading for each of them. 

Limitations

Many journals require you to include the limitations of your study in the discussion. Even if they don’t, there are good reasons to mention these in your paper.

Why limitations don’t have a negative connotation

A study’s limitations are points to be improved upon in future research. While some of these may be flaws in your method, many may be due to factors you couldn’t predict.

Examples include time constraints or small sample sizes. Pointing this out will help future researchers avoid or address these issues. This part of the discussion can also include any attempts you have made to reduce the impact of these limitations, as in this study .

How limitations add to a researcher's credibility

Pointing out the limitations of your study demonstrates transparency. It also shows that you know your methods well and can conduct a critical assessment of them.  

Implications and significance

The final paragraph of the discussion section should contain the take-home messages for your study. It can also cite the “strong points” of your study, to contrast with the limitations section.

Restate your hypothesis

Remind the reader what your hypothesis was before you conducted the study. 

How was it proven or disproven?

Identify your main findings and describe how they relate to your hypothesis.

How your results contribute to the literature

Were you able to answer your research question? Or address a gap in the literature?

Future implications of your research

Describe the impact that your results may have on the topic of study. Your results may show, for instance, that there are still limitations in the literature for future studies to address. There may be a need for studies that extend your findings in a specific way. You also may need additional research to corroborate your findings. 

Sample discussion section

This fictitious example covers all the aspects discussed above. Your actual discussion section will probably be much longer, but you can read this to get an idea of everything your discussion should cover.

Our results showed that the presence of cats in a household is associated with higher levels of perceived happiness by its human occupants. These findings support our hypothesis and demonstrate the association between pet ownership and well-being. 

The present findings align with those of Bao and Schreer (2016) and Hardie et al. (2023), who observed greater life satisfaction in pet owners relative to non-owners. Although the present study did not directly evaluate life satisfaction, this factor may explain the association between happiness and cat ownership observed in our sample.

Our findings must be interpreted in light of some limitations, such as the focus on cat ownership only rather than pets as a whole. This may limit the generalizability of our results.

Nevertheless, this study had several strengths. These include its strict exclusion criteria and use of a standardized assessment instrument to investigate the relationships between pets and owners. These attributes bolster the accuracy of our results and reduce the influence of confounding factors, increasing the strength of our conclusions. Future studies may examine the factors that mediate the association between pet ownership and happiness to better comprehend this phenomenon.

This brief discussion begins with a quick summary of the results and hypothesis. The next paragraph cites previous research and compares its findings to those of this study. Information from previous studies is also used to help interpret the findings. After discussing the results of the study, some limitations are pointed out. The paper also explains why these limitations may influence the interpretation of results. Then, final conclusions are drawn based on the study, and directions for future research are suggested.

How to make your discussion flow naturally

If you find writing in scientific English challenging, the discussion and conclusions are often the hardest parts of the paper to write. That’s because you’re not just listing up studies, methods, and outcomes. You’re actually expressing your thoughts and interpretations in words.

• How formal should it be?
• What words should you use, or not use?
• How do you meet strict word limits, or make it longer and more informative?

Always give it your best, but sometimes a helping hand can, well, help. Getting a professional edit can help clarify your work’s importance while improving the English used to explain it. When readers know the value of your work, they’ll cite it. We’ll assign your study to an expert editor knowledgeable in your area of research. Their work will clarify your discussion, helping it to tell your story. Find out more about AJE Editing.

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Writing a scientific paper.

• Writing a lab report
• INTRODUCTION

Writing a "good" discussion section

"discussion and conclusions checklist" from: how to write a good scientific paper. chris a. mack. spie. 2018., peer review.

• LITERATURE CITED
• Bibliography of guides to scientific writing and presenting
• Presentations
• Lab Report Writing Guides on the Web

This is is usually the hardest section to write. You are trying to bring out the true meaning of your data without being too long. Do not use words to conceal your facts or reasoning. Also do not repeat your results, this is a discussion.

• Present principles, relationships and generalizations shown by the results
• Point out exceptions or lack of correlations. Define why you think this is so.
• Show how your results agree or disagree with previously published works
• Discuss the theoretical implications of your work as well as practical applications
• State your conclusions clearly. Summarize your evidence for each conclusion.
• Discuss the significance of the results
•  Evidence does not explain itself; the results must be presented and then explained.
• Typical stages in the discussion: summarizing the results, discussing whether results are expected or unexpected, comparing these results to previous work, interpreting and explaining the results (often by comparison to a theory or model), and hypothesizing about their generality.
• Discuss any problems or shortcomings encountered during the course of the work.
• Discuss possible alternate explanations for the results.
• Avoid: presenting results that are never discussed; presenting discussion that does not relate to any of the results; presenting results and discussion in chronological order rather than logical order; ignoring results that do not support the conclusions; drawing conclusions from results without logical arguments to back them up. 

CONCLUSIONS

• Provide a very brief summary of the Results and Discussion.
• Emphasize the implications of the findings, explaining how the work is significant and providing the key message(s) the author wishes to convey.
• Provide the most general claims that can be supported by the evidence.
• Provide a future perspective on the work.
• Avoid: repeating the abstract; repeating background information from the Introduction; introducing new evidence or new arguments not found in the Results and Discussion; repeating the arguments made in the Results and Discussion; failing to address all of the research questions set out in the Introduction. 

WHAT HAPPENS AFTER I COMPLETE MY PAPER?

 The peer review process is the quality control step in the publication of ideas.  Papers that are submitted to a journal for publication are sent out to several scientists (peers) who look carefully at the paper to see if it is "good science".  These reviewers then recommend to the editor of a journal whether or not a paper should be published. Most journals have publication guidelines. Ask for them and follow them exactly.    Peer reviewers examine the soundness of the materials and methods section.  Are the materials and methods used written clearly enough for another scientist to reproduce the experiment?  Other areas they look at are: originality of research, significance of research question studied, soundness of the discussion and interpretation, correct spelling and use of technical terms, and length of the article.

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Mastering Your Dissertation pp 105–115 Cite as

How Do I Write the Discussion Chapter?

Reflecting on and Comparing Your Data, Recognising the Strengths and Limitations

• Sue Reeves   ORCID: orcid.org/0000-0002-3017-0559 3 &
• Bartek Buczkowski   ORCID: orcid.org/0000-0002-4146-3664 4  
• First Online: 19 October 2023

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The Discussion chapter brings an opportunity to write an academic argument that contains a detailed critical evaluation and analysis of your research findings. This chapter addresses the purpose and critical nature of the discussion, contains a guide to selecting key results to discuss, and details how best to structure the discussion with subsections and paragraphs. We also present a list of points to do and avoid when writing the discussion together with a Discussion chapter checklist.

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Cottrell S (2017) Critical thinking skills: effective analysis, argument and reflection, 3rd edn. Palgrave, London

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How To Write a Term Paper: A Guide That Works

30 June, 2020

16 minutes read

Author:  Mathieu Johnson

Once you’ve started your university career, you are going to be asked to present a term paper. What’s the difference between a term paper and a research paper? How can you write a good term? What’s the best way to structure it? Where can you find some tips to make the writing process faster? In this article, we’ll discuss a few tips to help you prepare a term paper quickly and professionally.

What Is a Term Paper… And What Is The First Step?

A term paper is a critical and analytical report on the topic or subject that you covered within the course of studies. It usually consists of two separate but equally important aspects: your own thoughts about the topic and a demonstration of your understanding of the existing literature. The main goal of this assignment is to summarize the material you learned and showcase your understanding of the topic. This aspect makes the term paper a universal instrument for assessing a student’s proficiency. It also explains why term papers cost so many points of your course grade.

We usually associate a term paper with a research paper , but although the concepts are quite similar, a research paper requires a more academic approach and a deeper investigation into the literature of your field of study.

To write an outstanding college term paper, you must understand that your professor has requested it in order to test your analytical thinking skills. You must collect relevant data, analyze it, and then make a summary or solve a particular problem. Such skills are highly relevant to the business world, so this type of the task is as practical as it is educational.

So, let’s start the preparation!

Before you begin writing

Unfortunately, there is no magical recipe that allows you to get everything done fast. You will need to choose the best way forward in whatever situation you find yourself, but here are some tips to help you prepare for the assignment.

To begin with, take the research stage seriously . Sometimes, when students are really interested in a topic, they only want to present their personal ideas about the problem. Unfortunately, if you’re not completely familiar with all the data from the various sources, you will need to reinvent the bicycle.

Term paper writing was never an easy ride. Well, not for our expert writers. Place an order with our term paper writing service and secure yourself an “A!”

In the initial stages of your research, investigate everything you can find on the topic . This may sound like a tall order, but you’ll find that it doesn’t actually entail that much reading. At this point you are only compiling the research, so you will be skimming through numerous prospects rather than reading them completely. Bear in mind that your aim is to get acquainted with the various aspects of your problem. The term paper summarizes the knowledge you gained within a course and requires to familiarize yourself with the research that other people have already made on your topic.

Thinking that your opinions are completely original and unique is quite egocentric, and it can get you into trouble. So, “your” thoughts about the problem are usually just somebody else’s statements that you have rephrased (or even a well-established academic concept!). Remember that your professor will be familiar with all the literature surrounding the issue: if you merely rewrite someone else’s thoughts and present them as your own (even if you don’t realize doing it), be prepared for criticism!

Applying a Structure To Your Term Paper

Once you have read all the leading authors and their approaches to your problem, it’s time to create a structure for your work. This is not yet an outline; you just need to decide what to write about. Sketch out the topic for the theoretical portion of your work and think about practical aspects and how you can approach the research in the best possible way.

At this point, you really need to call or email your supervisor . Your professor will have seen hundreds of term papers like yours (i.e., they have not yet been written, but a definite idea exists!) and will be prepared to give you feedback and advice. He or she will tell you what literature you have omitted, offer suggestions about what you should read, and give you feedback about your paper. It may well be that your approach has already occurred to somebody else, in which case there is no need to repeat it.

Choosing a Topic: Easy as Riding a Bike?

When you choose your topic, make sure you choose something that you are interested in . That’s our advice if you want a painless term paper. If you prefer to investigate a field that you’ve never really explored before, you can challenge yourself to do that, too. That might be sophisticated, but why not?

If you decide to investigate a topic or a problem that you are pretty familiar with, your writing will be more fluid. You will focus your attention on a specific aspect of the chosen field and expand your knowledge within that scope. On the contrary, choosing an unfamiliar subject matter can wash out your expertise.

Be prepared to change the topic if you find out that your research isn’t going anywhere. It might occur that you presuppose that your topic has a potential but somewhere at the stage of initial research, you find that it just won’t work. It’s always a good idea to consider two or three topics when you kick off the term paper writing – even if they are just different ways of examining the same problem. By doing this, you will be able to choose the best version, which may not be the one you started with at all!

Related Post: 100 Persuasive essay topics

Formulating a Thesis statement

Writing a proper thesis statement can also be challenging. To begin with, write down a couple of prominent ideas or concepts, then try to make rough drafts of them to see how they’ll work in the structural framework. You will probably find that one idea fits your style, interests, and knowledge base: you can choose that one as your thesis statement.

Remember that the thesis statement is the skeleton, the central concept of your paper. It is the elemental attribute of almost any academic paper – from master’s thesis to a simple five paragraph essay. If you do a thorough job on it, you will find that writing (and defending!) your argument is much easier.

Be aware that all of these stages are parts of a procedure – one leads to another. When writing a term paper, you should collect the material and wrap it up at the same time.

Planning – The Key To Success

Some people claim that they can write a term paper without any planning. In our opinion, this is impossible. If you don’t have a postgraduate degree and you aren’t a certified genius, you need to prepare an outline for your project. It may come as a surprise, but even people who claim otherwise actually prepare outlines – in their heads. But if you don’t have that much experience, use a pencil and your notebook to ensure that you don’t forget anything.

Don’t procrastinate on your College or University papers anymore. Get professional help with our essay writer !

That’s when we get to preparing your first draft . There’s only one thing to add here: do as many drafts as you need in order to achieve your goal. Understand that your aim is to create an excellent term paper and keep working at it until you are satisfied.

Term Paper Outline: Write Everything In The Proper Section!

In the Introduction , state the topic that you are going to investigate and the context of your work. This is the critical ‘selling’ moment of your work. In a nutshell, your introduction combined with a conclusion should give a sneak peek into what the whole paper is about. If your introduction is well-prepared, it will be quite complacent about the body of your project. The introduction must include an abstract that presents your thesis statement . You should explain your motivation (why should the reader be concerned about this problem?) , your methods (what scientific tools did you use?) , and the results (what you achieved) .

The Literature Review totally corresponds to its name – it is here to review the literature you compiled. Your professor will double check it to make sure that you understand the context of your argument. One more thing to add is: collect all the information you can! Ideally, you should read or at least glance through every book and author that you can find on the topic. Think of your task as a fascinating journey: if you approach it like that, reading hundreds of pages won’t seem like that much of a challenge.

In the Discussion , you must present the interpretations of the problem. Be honest, explain what you pieces of data you don’t agree with and what ideas and concepts you support. This section connects the dots between theory and practice when writing a term paper. Wherever possible, provide several interpretations of the subject matter, then choose the one(s) that are most relevant to the case you are presenting.

In the Body , focus on those arguments that prove your thesis statement. This section must be absolutely logical. If you have chosen a more complicated topic, use heading and sub-headings to improve the appearance of this section. While writing the body, keep your target audience (your professors) in mind. In other words, don’t just record the obvious causes/effects/solutions but also showcase your own findings – what you have discovered and how that proves your thesis statement. Demonstrate that you are familiar with the details and you will stun your readers with the prolific mastery of the topic.

Now, the Conclusion   is her to summarize both the content and the purpose of the paper. The most challenging part is not to make it too dry. Reiterate your thesis statement and briefly show how your results justified your proposition. At the very end, you can suggest a call to action or pose a rhetorical question or statement that leaves your reader wanting more.

What to do next?

When you have finished, reread your work a couple of times. You will almost certainly find a few faults, whether they are contextual, factual, syntactical, grammatical, or even simple spelling mistakes. A very useful tip is to wait for two or three days after writing your final draft to proofread it afterward. Your brain will have time to process the information, and you’ll be able to look at it with a fresh view.

When proofreading, take care to polish the structural problems. The skeleton (the logic and the thesis statement) should make sense. If they don’t, try to approach the problem from another perspective. The changes may take some time, but bear in mind that your objective is to produce professional work. Be patient!

After that, print the term paper. The human eye processes information differently on the paper than on a computer screen; that’s why you need to print it and take one final look for any possible mistakes. Even if you don’t see any serious defects, pay attention to formatting, punctuation, and synonyms. It’s an academic text, so make it shine!

Term Paper Sample

Be sure to check the sample of a term paper, completed by our writers. Use it as an example to perfect your own writing. Link:  Term Paper Sample: Consumer Buying Behavior .

The Do’s and Don’ts of Term Paper Writing

There you have the most important tips to help you succeed in writing a term paper. Now it’s up to you to stop reading and start writing!

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Writing a research paper on ethics is not an easy task, especially if you do not possess excellent writing skills and do not like to contemplate controversial questions. But an ethics course is obligatory in all higher education institutions, and students have to look for a way out and be creative. When you find an […]

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How to Write a Discussion Section for a Research Paper

We’ve talked about several useful writing tips that authors should consider while drafting or editing their research papers. In particular, we’ve focused on  figures and legends , as well as the Introduction ,  Methods , and  Results . Now that we’ve addressed the more technical portions of your journal manuscript, let’s turn to the analytical segments of your research article. In this article, we’ll provide tips on how to write a strong Discussion section that best portrays the significance of your research contributions.

What is the Discussion section of a research paper?

In a nutshell,  your Discussion fulfills the promise you made to readers in your Introduction . At the beginning of your paper, you tell us why we should care about your research. You then guide us through a series of intricate images and graphs that capture all the relevant data you collected during your research. We may be dazzled and impressed at first, but none of that matters if you deliver an anti-climactic conclusion in the Discussion section!

Are you feeling pressured? Don’t worry. To be honest, you will edit the Discussion section of your manuscript numerous times. After all, in as little as one to two paragraphs ( Nature ‘s suggestion  based on their 3,000-word main body text limit), you have to explain how your research moves us from point A (issues you raise in the Introduction) to point B (our new understanding of these matters). You must also recommend how we might get to point C (i.e., identify what you think is the next direction for research in this field). That’s a lot to say in two paragraphs!

So, how do you do that? Let’s take a closer look.

What should I include in the Discussion section?

As we stated above, the goal of your Discussion section is to  answer the questions you raise in your Introduction by using the results you collected during your research . The content you include in the Discussions segment should include the following information:

• Remind us why we should be interested in this research project.
• Describe the nature of the knowledge gap you were trying to fill using the results of your study.
• Don’t repeat your Introduction. Instead, focus on why  this  particular study was needed to fill the gap you noticed and why that gap needed filling in the first place.
• Mainly, you want to remind us of how your research will increase our knowledge base and inspire others to conduct further research.
• Clearly tell us what that piece of missing knowledge was.
• Answer each of the questions you asked in your Introduction and explain how your results support those conclusions.
• Make sure to factor in all results relevant to the questions (even if those results were not statistically significant).
• Focus on the significance of the most noteworthy results.
• If conflicting inferences can be drawn from your results, evaluate the merits of all of them.
• Don’t rehash what you said earlier in the Results section. Rather, discuss your findings in the context of answering your hypothesis. Instead of making statements like “[The first result] was this…,” say, “[The first result] suggests [conclusion].”
• Do your conclusions line up with existing literature?
• Discuss whether your findings agree with current knowledge and expectations.
• Keep in mind good persuasive argument skills, such as explaining the strengths of your arguments and highlighting the weaknesses of contrary opinions.
• If you discovered something unexpected, offer reasons. If your conclusions aren’t aligned with current literature, explain.
• Address any limitations of your study and how relevant they are to interpreting your results and validating your findings.
• Make sure to acknowledge any weaknesses in your conclusions and suggest room for further research concerning that aspect of your analysis.
• Make sure your suggestions aren’t ones that should have been conducted during your research! Doing so might raise questions about your initial research design and protocols.
• Similarly, maintain a critical but unapologetic tone. You want to instill confidence in your readers that you have thoroughly examined your results and have objectively assessed them in a way that would benefit the scientific community’s desire to expand our knowledge base.
• Recommend next steps.
• Your suggestions should inspire other researchers to conduct follow-up studies to build upon the knowledge you have shared with them.
• Keep the list short (no more than two).

How to Write the Discussion Section

The above list of what to include in the Discussion section gives an overall idea of what you need to focus on throughout the section. Below are some tips and general suggestions about the technical aspects of writing and organization that you might find useful as you draft or revise the contents we’ve outlined above.

Technical writing elements

• Embrace active voice because it eliminates the awkward phrasing and wordiness that accompanies passive voice.
• Use the present tense, which should also be employed in the Introduction.
• Sprinkle with first person pronouns if needed, but generally, avoid it. We want to focus on your findings.
• Maintain an objective and analytical tone.

Discussion section organization

• Keep the same flow across the Results, Methods, and Discussion sections.
• We develop a rhythm as we read and parallel structures facilitate our comprehension. When you organize information the same way in each of these related parts of your journal manuscript, we can quickly see how a certain result was interpreted and quickly verify the particular methods used to produce that result.
• Notice how using parallel structure will eliminate extra narration in the Discussion part since we can anticipate the flow of your ideas based on what we read in the Results segment. Reducing wordiness is important when you only have a few paragraphs to devote to the Discussion section!
• Within each subpart of a Discussion, the information should flow as follows: (A) conclusion first, (B) relevant results and how they relate to that conclusion and (C) relevant literature.
• End with a concise summary explaining the big-picture impact of your study on our understanding of the subject matter. At the beginning of your Discussion section, you stated why  this  particular study was needed to fill the gap you noticed and why that gap needed filling in the first place. Now, it is time to end with “how your research filled that gap.”

Discussion Part 1: Summarizing Key Findings

Begin the Discussion section by restating your  statement of the problem  and briefly summarizing the major results. Do not simply repeat your findings. Rather, try to create a concise statement of the main results that directly answer the central research question that you stated in the Introduction section . This content should not be longer than one paragraph in length.

Many researchers struggle with understanding the precise differences between a Discussion section and a Results section . The most important thing to remember here is that your Discussion section should subjectively evaluate the findings presented in the Results section, and in relatively the same order. Keep these sections distinct by making sure that you do not repeat the findings without providing an interpretation.

Phrase examples: Summarizing the results

• The findings indicate that …
• These results suggest a correlation between A and B …
• The data present here suggest that …
• An interpretation of the findings reveals a connection between…

Discussion Part 2: Interpreting the Findings

What do the results mean? It may seem obvious to you, but simply looking at the figures in the Results section will not necessarily convey to readers the importance of the findings in answering your research questions.

The exact structure of interpretations depends on the type of research being conducted. Here are some common approaches to interpreting data:

• Identifying correlations and relationships in the findings
• Explaining whether the results confirm or undermine your research hypothesis
• Giving the findings context within the history of similar research studies
• Discussing unexpected results and analyzing their significance to your study or general research
• Offering alternative explanations and arguing for your position

Organize the Discussion section around key arguments, themes, hypotheses, or research questions or problems. Again, make sure to follow the same order as you did in the Results section.

Discussion Part 3: Discussing the Implications

In addition to providing your own interpretations, show how your results fit into the wider scholarly literature you surveyed in the  literature review section. This section is called the implications of the study . Show where and how these results fit into existing knowledge, what additional insights they contribute, and any possible consequences that might arise from this knowledge, both in the specific research topic and in the wider scientific domain.

Questions to ask yourself when dealing with potential implications:

• Do your findings fall in line with existing theories, or do they challenge these theories or findings? What new information do they contribute to the literature, if any? How exactly do these findings impact or conflict with existing theories or models?
• What are the practical implications on actual subjects or demographics?
• What are the methodological implications for similar studies conducted either in the past or future?

Your purpose in giving the implications is to spell out exactly what your study has contributed and why researchers and other readers should be interested.

Phrase examples: Discussing the implications of the research

• These results confirm the existing evidence in X studies…
• The results are not in line with the foregoing theory that…
• This experiment provides new insights into the connection between…
• These findings present a more nuanced understanding of…
• While previous studies have focused on X, these results demonstrate that Y.

Step 4: Acknowledging the limitations

All research has study limitations of one sort or another. Acknowledging limitations in methodology or approach helps strengthen your credibility as a researcher. Study limitations are not simply a list of mistakes made in the study. Rather, limitations help provide a more detailed picture of what can or cannot be concluded from your findings. In essence, they help temper and qualify the study implications you listed previously.

Study limitations can relate to research design, specific methodological or material choices, or unexpected issues that emerged while you conducted the research. Mention only those limitations directly relate to your research questions, and explain what impact these limitations had on how your study was conducted and the validity of any interpretations.

Possible types of study limitations:

• Insufficient sample size for statistical measurements
• Lack of previous research studies on the topic
• Methods/instruments/techniques used to collect the data
• Limited access to data
• Time constraints in properly preparing and executing the study

After discussing the study limitations, you can also stress that your results are still valid. Give some specific reasons why the limitations do not necessarily handicap your study or narrow its scope.

Phrase examples: Limitations sentence beginners

• “There may be some possible limitations in this study.”
• “The findings of this study have to be seen in light of some limitations.”
•  “The first limitation is the…The second limitation concerns the…”
•  “The empirical results reported herein should be considered in the light of some limitations.”
• “This research, however, is subject to several limitations.”
• “The primary limitation to the generalization of these results is…”
• “Nonetheless, these results must be interpreted with caution and a number of limitations should be borne in mind.”

Discussion Part 5: Giving Recommendations for Further Research

Based on your interpretation and discussion of the findings, your recommendations can include practical changes to the study or specific further research to be conducted to clarify the research questions. Recommendations are often listed in a separate Conclusion section , but often this is just the final paragraph of the Discussion section.

Suggestions for further research often stem directly from the limitations outlined. Rather than simply stating that “further research should be conducted,” provide concrete specifics for how future can help answer questions that your research could not.

Phrase examples: Recommendation sentence beginners

• Further research is needed to establish …
• There is abundant space for further progress in analyzing…
• A further study with more focus on X should be done to investigate…
• Further studies of X that account for these variables must be undertaken.

Consider Receiving Professional Language Editing

As you edit or draft your research manuscript, we hope that you implement these guidelines to produce a more effective Discussion section. And after completing your draft, don’t forget to submit your work to a professional proofreading and English editing service like Wordvice, including our manuscript editing service for  paper editing , cover letter editing , SOP editing , and personal statement proofreading services. Language editors not only proofread and correct errors in grammar, punctuation, mechanics, and formatting but also improve terms and revise phrases so they read more naturally. Wordvice is an industry leader in providing high-quality revision for all types of academic documents.

For additional information about how to write a strong research paper, make sure to check out our full  research writing series !

Wordvice Writing Resources

• How to Write a Research Paper Introduction 
• Which Verb Tenses to Use in a Research Paper
• How to Write an Abstract for a Research Paper
• How to Write a Research Paper Title
• Useful Phrases for Academic Writing
• Common Transition Terms in Academic Papers
• Active and Passive Voice in Research Papers
• 100+ Verbs That Will Make Your Research Writing Amazing
• Tips for Paraphrasing in Research Papers

Additional Academic Resources

•   Guide for Authors.  (Elsevier)
•  How to Write the Results Section of a Research Paper.  (Bates College)
•   Structure of a Research Paper.  (University of Minnesota Biomedical Library)
•   How to Choose a Target Journal  (Springer)
•   How to Write Figures and Tables  (UNC Writing Center)

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How to Write an Efficient Discussion?

Academy for Medical Sciences of Bosnia and Herzegovina (AMNuBiH), Sarajevo, Bosnia and Herzegovina

Writing of scientific articles requires high competence and scientific awareness, and the respect of scientific patterns of behavior. Every article should essentially be followed by the IMRAD structure, which is generally represented, with minor modifications, in the entire modern scientific publishing. Writing articles must follow the thread, have a meaningful beginning and end, and from each and every part of the context. Also, it is indicate the benefits of the paper, to its defect, defining ambiguous points that would have the process for further analysis in some subsequent studies by the same or another group of authors. It means, the chapter - Discussion represents the heart of every scientific article. The writing of the discussion itself must point to the specificity of the results of the work itself. Author wants to point out the importance of quality description of chapter Discussion, when scientists prepare their articles with presenting own results comparing it with results of other authors with similar topic.

Usual way in writing of articles for publishing in biomedical journals is to follow the instructions: – Vancouver’s rules and Uniform Requirements for Manuscripts submitted to Biomedical Journals: Writing and Editing for Biomedical Publication ( 1 , 2 ). Writing of scientific paper requires high competence and scientific awareness, and the respect of scientific patterns of behavior.

Every paper should essentially be followed by the IMRAD structure, which is generally represented, with minor modifications, in the entire modern scientific publishing. The concept of pointing out that the usual order of sections is contained in the abbreviation “IMRAD” :

• I - Introduction,
• M - Methods (or Methods and Materials),
• R - Results,
• D - Discussion and Conclusion.

The abstract does not contain discussion. Although it is a common fact, editors around the world can point out that today is one thing that is not so rare. The idea, pointing to clear goals, setting the hypothesis itself, and conducting the research itself, are important steps in scientific writing. But, the analysis of the results obtained, and the pointing of these results, as well as, comparison with the results of other studies that deal with the same or similar topic requires skill and high expertise in a particular field.

It is very important that when writing the paper itself, the author has a writing style, which differs from the individual to the individual, and essentially reflects the way the author’s thinking.

Clarity, simplicity, briefness, precision and unity are the inevitable features of a scientific style, while the language of writing must be more precise ( 3 ). Selection of verb time depends on which results are described. If known, what has already been published, should be in the present time (Introduction and Discussion) and, if described, their own results should be described in the past time (Material and methods), with recommendation to use active instead of passive, except in summary, where the use of passive language is recommended ( 3 ).

Writing must follow the thread, have a meaningful beginning and end, and from each and every part of the context, indicate the benefits of the paper, to its defect, defining ambiguous points that would have the process for further analysis in some subsequent studies by the same or another group of authors ( 1 ).

The writing of the discussion itself must point to the specificity of the results of the work itself, whether they are going to work with previously published articles or are different. If it is different to point to the details of the statistical processing, or to point to the level of significance that has become, and in some cases to the intensity and significance of the processed method.

It is very important that authors do not repeat the presented results, but it is only necessary to point to those exceptions that do not confirm the rule. It is very important to elaborate the results that are important because they carry the power of an article. The results that are not confirmed by statistical processing should not be in the center of attention ( 1 , 2 ).

The discussion should essentially address the theoretical and practical consequences of the results, and the conclusions themselves should be presented as briefly and clearly as possible, with individual argumentation. The purpose of the discussion should be the relation between the observed results and the facts) ( 3 ).

The discussion should not contain historical facts about a phenomenon or topic of writing (those who are not important to the survey itself), should not repeat things that are known to a wider population or which are not at an adequate academic level. A comparison of the results obtained with the research should be done with recognized studies in the reference index databases.

Comparing own results with results from predatory or low-quality journals (primarily a journal in which the papers does not undergo peer review) is contextually meaningless, and it is virtually impossible to get a good result ( 2 ).

If only the research has, or may have, a large bias selection, it must be shown, because every original scientific paper is an article that could be included in a meta-analysis or systematic review for the second day so that it may be re-established the repetition of bias, that is, the inability to come to conclusions that could be of great importance in the practice tomorrow.

The discussion must not be too long, it must not be too short.

The discussion must be closely related to the subject matter, must not depart from it, and must be a service. It must not exceed the sum of other parts (Introduction, Material and methods, Results) and must be written in six to seven paragraphs.

Each paragraph should not contain more than two hundred words. Paragraphs can be divided into three types generally ( 4 , 5 , 6 ):

• Introductory paragraph,
• Intermediate paragraphs,
• Concluding paragraph

Sentences should be clear, with no undetermined things that can be accidentally different. Quite quantitatively, each sentence should not exceed 25-30 words ( 4 ). Through long-lasting experience, the recommendation would be to not use the terms in the writing of the discussion, which are closely related to a certain spatiality or subspecialty, because the work itself must be interesting and clear to the general public, which does not mean that the work should not be written in an academic style.

Many authors have addressed the recommendations of writing a certain part of the work, and young researchers must first learn the basics of the writing methodology, because without it will work for sure many defects ( 7 ). The shortcomings happen even to the most experienced researchers ( 2 ).

A checklist has been developed, which can be helpful to the author when writing the work (CONSORT checklist or STROBE checklist) ( 1 ).

For authors who do not come from an English-speaking area, and the work is translated from a less professional person, it is imperative that they themselves participate in the translation of the Discussion, because the translation of the scientific work sometimes knows that it is defective, not as good as the original, and not shows what should be displayed, that is, does not point things out of importance.

The peer review discussions, although the primary reviewers pay the most attention to the methodology of conducting the research and the results, must be very well made, because although many underestimates.

Instead of conclusion we can say the fact is: the Discussion represents the heart of every scientific article.

Conflict of interest:

none declared.

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How to Write a Term Paper 101: A Tutorial to Takeover

As the end of the semester draws closer, many students are losing their sleep over the thought of writing a term paper. But you’re worrying pointlessly because  PaperPerk  has brought expert help to your doorstep! 

Our comprehensive guide on how to write a term paper is sure to help you with every step. So read this article thoroughly because we cover everything from definition to steps on composition and templates with examples.

Table of Contents

What Is a Term Paper?

A term paper is a written project required at the end of a semester. It is designed to evaluate a student’s knowledge and understanding of a particular subject. Typically, it takes the form of a discussion or analysis of an assigned topic. 

But it can also resemble a scientific report,  reflective essay , or even a research paper. As an essential component of a student’s academic journey, a term paper is characterized by its in-depth exploration of a specific subject matter.

Key Characteristics

One of the key features of a term paper is that it requires a significant amount of research , as it aims to provide a comprehensive understanding of the topic. This research-intensive nature of the term paper sets it apart from other academic assignments. 

Additionally, term papers demand technical writing skills, as they need to be well-organized, structured, and adhere to specific formatting requirements. A high-quality term paper should be well-written, thoroughly researched, and analytical. 

It should demonstrate critical thinking and provide valuable insights into the subject matter. With an Impactful term paper, a student showcases their ability to synthesize and analyze information, ultimately contributing to their overall academic success.

How to Write a Term Paper: A Comprehensive Guide

The biggest step in learning how to write a term paper is to understand the importance of creating a term paper outline. This  research paper outline  is the beacon that will guide through your writing process. The following part of this post contains steps on composing an outline and its component. 

How to Write a Term Paper: Outlining a Term Paper

Below are the essential components of an outline. Once you gather your information, you’ll incorporate it within these compartments to avoid creating a chaotic cluster of random data. 

Introduction

Let’s look at these a bit more closely and understand how to use these elements in the best way. 

Also known as the  title page , the cover page of a term paper is the first impression of the paper. It provides all the necessary information about the paper along with a neat and professional look. It should include the following information:

• Title of the paper
• Course name and code
• Instructor’s name
• Date of submission

Steps to compose a cover page:

• Centrally align the title of your paper in the middle of the page.
• Add your name, course name, and number below the title.
• Include your instructor’s name and the date of submission at the bottom.

You might be required to add more than these common elements if your professor asks you to. Many students additionally write the name of the university, department or other relevant details. 

The abstract is a brief summary of your term paper, usually between 150-250 words. It should highlight the main points, including the research question, methods, results, and conclusions. 

Using an  abstract  optimally allows readers to quickly grasp the main points and significance of your term paper. The abstract is usually placed at the beginning of the paper, right after the cover page. 

Steps to compose an abstract:

• Write a concise summary of your paper’s purpose and research question.
• Briefly describe the methods used in your research.
• Summarize the main findings or results.
• Conclude with a brief statement of your paper’s implications or significance.

Ensure that all the information you incorporate within your abstract accurately reflects the content and findings within your paper. Double-check that there is consistency between the abstract and the main body of the paper in terms of the research objectives, methodology, and conclusions. 

The  introduction  sets the stage for your term paper. It provides background information, states the research question, depicts the purpose of the study and explains the paper’s significance. 

Steps to compose an introduction:

• Begin with a hook to capture the reader’s attention.
• Provide background information on your topic.
• Clearly state your research question.
• Explain the significance of your research and its contribution to the field.

The body of your term paper is where you present your arguments , evidence, and analysis. It should be organized into sections or subheadings, each focusing on a specific aspect of your research.

Steps to compose the body:

• Organize your content into logical sections or subheadings.
• Present your arguments and support them with evidence from your research.
• Analyze the evidence and explain its relevance to your research question.
• Use appropriate citations to acknowledge the sources of your information.

The results section presents the outcomes and the findings of your research study. It should be clear, concise, and focused on the data collected during your study.

Steps to compose the results section:

• Summarize the data collected during your research.
• Use tables, charts, or graphs to visually represent your findings.
• Describe any patterns, trends, or relationships observed in the data.
• Ensure that your results are relevant to your research question.
• Avoid repetition of any information. 

The  discussion section  interprets the results of your term paper and explains their implications. It should also address any limitations of your research and suggest areas for future study.

Steps to compose the discussion section:

• Interpret your results and explain their significance.
• Discuss any limitations or weaknesses in your research.
• Compare your findings to previous studies and explain any differences.
• Suggest areas for future research based on your findings.

The  conclusion  brings your term paper to a close by summarizing the main points. This final section of your paper also restates the significance of your research.

Steps to compose a conclusion:

• Restate your research question and summarize the main points of your paper.
• Emphasize the significance of your research and its contribution to the field.
• Offer recommendations or suggestions for future research.
• End with a strong closing statement that leaves a lasting impression on the reader.

By following this comprehensive guide, you can write a well-structured and impactful term paper that demonstrates your understanding of the subject and contributes valuable insights to the field.

How to Write a Term Paper Proposal: A Tutorial

A term paper proposal serves as a blueprint for your research. It helps in organizing your thoughts and ideas. Lets focus on the essential features of a term paper proposal and understand steps on how to compose each part.

Essential Features of a Term Paper Proposal

Relevance and importance.

The title of your term paper proposal should attract your readers and provide them with a clear idea of your work. It should be clear, concise, and accurately reflect the subject of your research.

Steps to compose a title:

• Identify the main topic or theme of your research.
• Choose relevant keywords that represent the key concepts of your research.
• Combine these keywords to create a clear and informative title.
• Ensure that your  title  is not too long or overly complex.
• Consider your audience’s ability to understand your title.

The objectives section outlines the specific goals of your research. These goals should be clear, measurable, and achievable within the scope of your term paper.

Steps to compose objectives:

• Begin by stating the general purpose of your research.
• Break down this purpose into specific, measurable objectives.
• Ensure that your objectives are achievable within the timeframe and resources available for your term paper.
• Keep your objectives focused and relevant to your research question.

The relevance and importance section demonstrates the significance of your research within the context of your field of study. It should explain why your research is necessary and how it contributes to the existing body of knowledge.

Steps to compose the relevance and importance section:

• Explain the context of your research by providing background information on the topic.
• Identify gaps or limitations in the existing literature that your research aims to address.
• Explain how your research contributes to the field by offering new insights or perspectives.
• Emphasize the potential impact of your research on the broader academic community or society as a whole.

Putting It All Together: Writing a Term Paper Proposal

Now that you clearly understand the essential features of a term paper  proposal , it’s time to put it all together. Follow these steps to create a well-structured and compelling proposal:

• Begin by writing a clear and concise title that accurately reflects the subject of your research.
• Compose a brief introduction that overviews your research topic and its significance. This introduction should also include a clear statement of your research question.
• Outline the specific objectives of your research, ensuring that they are clear, measurable, and achievable within the scope of your term paper.
• Explain the relevance and importance of your research by demonstrating its significance within your field of study. Highlight the gaps or limitations in the existing literature that your research aims to address.
• Provide a brief overview of your research methodology, including the methods you plan to use for data collection and analysis.
• Include a tentative timeline for your research, outlining the milestones and deadlines for each project stage.
• Conclude your proposal with a summary of the main points and a restatement of the significance of your research.

By following these comprehensive steps, you can create a well-structured and persuasive term paper proposal that demonstrates the importance of your research and sets the stage for a successful term paper.

How to Write a Term Paper: Formatting

A term paper format refers to the set of rules and standards that dictate the structure and presentation of a term paper. Formatting is essential to learn how to write a term paper as it ensures consistency, enhances readability, and maintains a professional appearance. 

A proper structure allows readers to concentrate on the content rather than the presentation. Several formatting styles are used in term papers, with the American Psychological Association (APA) style and the Modern Language Association (MLA) style being the most common.

Using APA Style in a Term Paper:

• Choose a standard font, such as 11-point Calibri, 11-point Arial, or 12-point Times New Roman.
• Apply double-spacing throughout the paper, including the abstract, main text, quotes, tables, figures, and references.
• Create a title page containing the paper’s title, author’s name, affiliated institution, and a running head.
• Organize the content using headings that adhere to  APA guidelines for different heading levels.
• Incorporate the author-date citation method for in-text citations and format the reference list according to APA guidelines.

Using MLA Style in a Term Paper:

• Opt for a standard font, such as 12-point Times New Roman.
• Double-space the entire paper, including the main text, quotes, and the Works Cited page.
• Include a header with the last name of the author and page number on the top right corner of all pages.
• Use parenthetical citations within the text and format according to  MLA guidelines .
• Follow MLA guidelines for formatting headings and subheadings, if applicable.

Adhering to the appropriate style guide when formatting term papers is crucial for maintaining academic integrity and ensuring that your work is easily comprehended and properly cited.

Choosing the Perfect Term Paper Topics

Writing a term paper can be a daunting task, but choosing the right term paper topics can make all the difference. In this part, we will provide you with some useful tips and tricks to make the process as smooth as possible.

The Starting Point

In most cases, students are assigned term papers by their professors. These topics are related to course outline to assess pupil’s understanding of the course material. As well as their ability to think critically and conduct research on a specific subject. 

Other times, teachers provide students a chance to choose a topic of their liking. But before you go on and pick a topic for your term paper, put the following concerns at the forefront. 

• The course objective 
• Your own interest. 

The Course Objective

Your term paper is essentially assigned to assess your command on the subject. Prioritize your course outline or objective before picking your  research paper topics . This will ensure that your paper is relevant and reflects what you have learnt so far about the subject. 

Your Interests

Your personal interests play a significant role in the success of your term paper. When you choose a topic that genuinely interests you, you are more likely to engage in  writing a research paper . This enthusiasm will not only make the writing process more enjoyable but also result in a higher quality term paper. 

Before picking a specific topic, make sure to conduct thorough research and align your personal liking to your course objective. The following tips on how to pick the perfect term paper topic will assist you in acing your grade.

Tips for Choosing the Perfect Term Paper Topic

While picking a topic for yourself, be mindful of certain things:

Adjusting Topic Length

Consider if the topic would adjust your required length for a term paper. Suppose you’re to write a  10-page research paper , what kind of topic would adjust within those 10 pages? Registering the narrowness or broadness of the topic can help.

Authentic Resources

The second thing you need to consider is the resources of your information. Check if the source you’re working with is authentic. Reliable  sources for a research paper  include academic journals, books, think tanks, and reputable websites.

Complexity of the Subject

To ensure the clarity of your topic, consider its complexity. It is important that the chosen subject can be effectively presented to your audience. Additionally, ensure that you have a solid understanding of the subject matter yourself.

By considering the length, resources, and complexity of your chosen topic, you can ensure that your term paper is engaging, informative, and well-researched. So, take the time to select the perfect topic and get ready to ace your term paper!

How to Write a Term Paper: A Template With Example

This template also contains examples that are highlighted in a different color. 

Title Page 

Abstract .

• Remember to never exceed the abstract more than 250 words.

1.1 Background

1.2 problem statement, 1.3 objectives, 2. literature review, 3. methodology, 5. discussion, 6. conclusion, 7. references.

• The references section uses the appropriate citation style (e.g., APA, MLA, Chicago).

8. Appendices

• If necessary, this section includes additional material such as raw data, survey questionnaires, interview transcripts, or any other supplementary information that supports the research.

This guide on how to write a term paper must have been helpful to you. But we understand that wrapping your head around something so detailed can be difficult when you’re stressed out. And most students are stressed out by the end of the semester due to multiple deadlines.  That’s why we have brought you our  term paper writing service  so you can relax and focus more on your upcoming exams. Our experts are dedicated to helping students excel academically with quality content and on-time submission. Check us out today and bid goodbye to academic worries!

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How to Write a Discussion Section: Writing Guide

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The discussion section of a research paper is where the author analyzes and explains the importance of the study's results. It presents the conclusions drawn from the study, compares them to previous research, and addresses any potential limitations or weaknesses. The discussion section should also suggest areas for future research.

Everything is not that complicated if you know where to find the required information. We’ll tell you everything there is to know about writing your discussion. Our easy guide covers all important bits, including research questions and your research results. Do you know how all enumerated events are connected? Well, you will after reading this guide we’ve prepared for you!

What Is in the Discussion Section of a Research Paper

The discussion section of a research paper can be viewed as something similar to the conclusion of your paper. But not literal, of course. It’s an ultimate section where you can talk about the findings of your study. Think about these questions when writing:

• Did you answer all of the promised research questions?
• Did you mention why your work matters?
• What are your findings, and why should anyone even care?
• Does your study have a literature review?

So, answer your questions, provide proof, and don’t forget about your promises from the introduction. 

How to Write a Discussion Section in 5 Steps

How to write the discussion section of a research paper is something everyone googles eventually. It's just life. But why not make everything easier? In brief, this section we’re talking about must include all following parts:

• Answers for research questions
• Literature review
• Results of the work
• Limitations of one’s study
• Overall conclusion

Indeed, all those parts may confuse anyone. So by looking at our guide, you'll save yourself some hassle.  P.S. All our steps are easy and explained in detail! But if you are looking for the most efficient solution, consider using professional help. Leave your “ write my research paper for me ” order at StudyCrumb and get a customized study tailored to your requirements.

Step 1. Start Strong: Discussion Section of a Research Paper

First and foremost, how to start the discussion section of a research paper? Here’s what you should definitely consider before settling down to start writing:

• All essays or papers must begin strong. All readers will not wait for any writer to get to the point. We advise summarizing the paper's main findings.
• Moreover, you should relate both discussion and literature review to what you have discovered. Mentioning that would be a plus too.
• Make sure that an introduction or start per se is clear and concise. Word count might be needed for school. But any paper should be understandable and not too diluted.

Step 2. Answer the Questions in Your Discussion Section of a Research Paper

Writing the discussion section of a research paper also involves mentioning your questions. Remember that in your introduction, you have promised your readers to answer certain questions. Well, now it’s a perfect time to finally give the awaited answer. You need to explain all possible correlations between your findings, research questions, and literature proposed. You already had hypotheses. So were they correct, or maybe you want to propose certain corrections? Section’s main goal is to avoid open ends. It’s not a story or a fairytale with an intriguing ending. If you have several questions, you must answer them. As simple as that.

Step 3. Relate Your Results in a Discussion Section

Writing a discussion section of a research paper also requires any writer to explain their results. You will undoubtedly include an impactful literature review. However, your readers should not just try and struggle with understanding what are some specific relationships behind previous studies and your results.  Your results should sound something like: “This guy in their paper discovered that apples are green. Nevertheless, I have proven via experimentation and research that apples are actually red.” Please, don’t take these results directly. It’s just an initial hypothesis. But what you should definitely remember is any practical implications of your study. Why does it matter and how can anyone use it? That’s the most crucial question.

Step 4. Describe the Limitations in Your Discussion Section

Discussion section of a research paper isn’t limitless. What does that mean? Essentially, it means that you also have to discuss any limitations of your study. Maybe you had some methodological inconsistencies. Possibly, there are no particular theories or not enough information for you to be entirely confident in one’s conclusions.  You might say that an available source of literature you have studied does not focus on one’s issue. That’s why one’s main limitation is theoretical. However, keep in mind that your limitations must possess a certain degree of relevancy. You can just say that you haven’t found enough books. Your information must be truthful to research.

Step 5. Conclude Your Discussion Section With Recommendations

Your last step when you write a discussion section in a paper is its conclusion, like in any other academic work. Writer’s conclusion must be as strong as their starting point of the overall work. Check out our brief list of things to know about the conclusion in research paper :

• It must present its scientific relevance and importance of your work.
• It should include different implications of your research.
• It should not, however, discuss anything new or things that you have not mentioned before.
• Leave no open questions and carefully complete the work without them.

Discussion Section of a Research Paper Example

All the best example discussion sections of a research paper will be written according to our brief guide. Don’t forget that you need to state your findings and underline the importance of your work. An undoubtedly big part of one’s discussion will definitely be answering and explaining the research questions. In other words, you’ll already have all the knowledge you have so carefully gathered. Our last step for you is to recollect and wrap up your paper. But we’re sure you’ll succeed!

How to Write a Discussion Section: Final Thoughts

Today we have covered how to write a discussion section. That was quite a brief journey, wasn’t it? Just to remind you to focus on these things:

• Importance of your study.
• Summary of the information you have gathered.
• Main findings and conclusions.
• Answers to all research questions without an open end.
• Correlation between literature review and your results.

But, wait, this guide is not the only thing we can do. Looking for how to write an abstract for a research paper  for example? We have such a blog and much more on our platform.

Our academic writing service is just a click away. We are proud to say that our writers are professionals in their fields. Buy a research paper and our experts can provide prompt solutions without compromising the quality.

Joe Eckel is an expert on Dissertations writing. He makes sure that each student gets precious insights on composing A-grade academic writing.

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Discussion Section of a Research Paper: Frequently Asked Questions

1. how long should the discussion section of a research paper be.

Our discussion section of a research paper should not be longer than other sections. So try to keep it short but as informative as possible. It usually contains around 6-7 paragraphs in length. It is enough to briefly summarize all the important data and not to drag it.

2. What's the difference between the discussion and the results?

The difference between discussion and results is very simple and easy to understand. The results only report your main findings. You stated what you have found and how you have done that. In contrast, one’s discussion mentions your findings and explains how they relate to other literature, research questions, and one’s hypothesis. Therefore, it is not only a report but an efficient as well as proper explanation.

3. What's the difference between a discussion and a conclusion?

The difference between discussion and conclusion is also quite easy. Conclusion is a brief summary of all the findings and results. Still, our favorite discussion section interprets and explains your main results. It is an important but more lengthy and wordy part. Besides, it uses extra literature for references.

4. What is the purpose of the discussion section?

The primary purpose of a discussion section is to interpret and describe all your interesting findings. Therefore, you should state what you have learned, whether your hypothesis was correct and how your results can be explained using other sources. If this section is clear to readers, our congratulations as you have succeeded.

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Discussion Paper: Write It Perfectly

• May 21, 2020
• Posted by: admin
• Category: Blog ,

In most cases, students believe that writing a discussion paper is easier than writing college paper of any other kind. They are right to some extent. A discussion paper gives you a unique opportunity to discuss an opinion, doesn’t matter how common it is.

However, there is a danger in the belief that a discussion paper should be easy-to-understand. Many students don’t take it in a serious manner, and as a result, they fail. Other students take it in a too serious way, and this is not the right approach, as well.

What Is a Discussion Paper — Definition and Purpose

So, what is a discussion paper? A discussion paper is actually a discussion about some topic. Are you surprised? Yes, this is the definition, however, if you don’t have good writing skills, it is not so easy to write it. But don’t worry, that’s why we collected here some tips that will definitely help you.

First of all, never select a topic that doesn’t touch you. Even if you like the topic, you might find it complicated to write about it. If you want to write a nice discussion paper, you should express different ideas and opinions on the given topic and provide a discussion based on those ideas and opinions. So, it is always better to select something that you really like. Now, let us move to more detailed instructions and tips.

How to Write a Discussion Paper Step-by-Step

Don`t hurry to start writing. First, check properly all the sources and select materials that you might need to use. Are there new opinions on the topic? Which of them do you support? Which of them do you consider to be not okay? How can you arrange them in a way to build a nice meaningful discussion paper?

Select those materials that are reliable enough. Rainbow press, for example, could be good just for a very limited number of topics. But in most cases, you should rely on expert opinions. Select those that you might want to use to substantiate your ideas that you want to discuss. Arrange them in a logical order. Usually, you might want to arrange them in order, appropriate for the discussion logics. Make a plan.

Many students don’t write a plan at all, and this is a huge mistake. When you are working on your essay plan, you are not only arranging your thoughts, but you create the structure for your paper. It is easier to remake a frame rather than the entire construction. So, if there is something that needs to be changed, you better change it at the planning stage rather than when the paper is written.

An Intriguing Introduction Is a Key to Success

Now, you have a plan and can move to your introduction. But how to start a discussion paper? Consider what you want to write. Why is the topic interesting? May your reader find it useful? Can you add some funny or intriguing story to introduce the topic or at least some opinions? If yes, add it. Personal stories always make a better effect than generalizations.

Move to the Main Part

After having hooked your reader, move to the main part. Your task here is to introduce the topic, the main ideas, and expert opinions, as well as your views, and to provide a discussion of those ideas and opinions that you have mentioned. You have several ways to discuss:

• You can discuss everything idea by idea, providing its advantages and disadvantages;
• You might want to give your personal idea and base the discussion on it, and you may use other ideas to prove your opinion.
• You can group all ideas based on some features and discuss the ideas groups.
• Or you can invent your own unique method of organizing your discussion paper.

However, doesn’t matter what way you select, there are some rules that apply to any kind of paper. Whatever you are writing, you should follow these rules, because those are the basics of good writing:

• Be consistent, because jumping from one idea to another is confusing and doesn’t make your paper logical.
• Discuss all those ideas mentioned by you, don’t leave any idea or opinion unattended.
• Write in an easy-to-read manner — you are writing an essay, not a scientific work.
• Structure your work logically — the reader should not look for information too long.
• Make an excellent introduction and a nice conclusion for your discussion paper.

By the way, now, we came to the point when we need to speak more about a conclusion. So, how to end a discussion paper in a nice way? How not to spoil all impression from your essay with a poorly written conclusion?

Well, if you have managed to move so far, then, a proper conclusion should not cause any difficulties. Just sum up everything. What was the topic? Why was it relevant? What are the ideas about the issue and how do they support your idea or contradict it? Which conclusion have you made? And that’s it, you have written a high-quality, unique paper.

Discussion Paper Format and Its Details

So, you have already noticed, that the discussion paper format isn’t much different from a usual paper format. The only thing, which differs here, is the discussion presence. You give different, sometimes contrasting ideas, as well, you discuss them from different points of view in a search for a solution.

Is the Paper Ready for Submitting?

However, don’t hurry to submit your paper. You have just read how to write a good discussion paper, but you haven’t made one crucial step yet. You forgot about proofreading! Read everything once more, pay attention to each word and phrase. After you complete proofreading, you can submit your paper with peace in mind.

If you get a discussion paper as an assignment, don’t panic. Follow the simple tips from our experts who work at custom essay writing services , and just make sure you do your best. Don’t forget as well to include any citations if they are required. Now, when your paper is ready, check it once more for the compliance with the requirements, and submit it.

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• Published: 01 March 2024

Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19

• Aimee L. Hanson   ORCID: orcid.org/0000-0002-0231-8771 1 , 2 ,
• Matthew P. Mulè 1 , 2 , 3 ,
• Hélène Ruffieux   ORCID: orcid.org/0000-0002-7113-2540 4 ,
• Federica Mescia   ORCID: orcid.org/0000-0002-2759-4027 1 , 2 ,
• Laura Bergamaschi 1 , 2 ,
• Victoria S. Pelly 1 , 2 ,
• Lorinda Turner 1 , 2 ,
• Prasanti Kotagiri 1 , 2 ,
• Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration ,
• Berthold Göttgens   ORCID: orcid.org/0000-0001-6302-5705 5 ,
• Christoph Hess   ORCID: orcid.org/0000-0003-0364-8825 1 , 2 , 6 , 7 ,
• Nicholas Gleadall 8 , 9 ,
• John R. Bradley 2 , 10 , 11 ,
• James A. Nathan   ORCID: orcid.org/0000-0002-0248-1632 1 , 2 ,
• Paul A. Lyons   ORCID: orcid.org/0000-0001-7035-8997 1 , 2 ,
• Hal Drakesmith   ORCID: orcid.org/0000-0002-8503-6103 12 &
• Kenneth G. C. Smith   ORCID: orcid.org/0000-0003-3829-4326 1 , 2   nAff13   nAff14  

Nature Immunology volume  25 ,  pages 471–482 ( 2024 ) Cite this article

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• Chronic inflammation
• Erythropoiesis
• Viral infection

Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1–3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes. Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.

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Prolonged ill health following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, often termed post-acute sequelae of Coronavirus Disease 2019 (COVID-19; PASC) or ‘long COVID’, is defined as the unexplained continuation or development of symptoms ≥3 months from COVID-19 onset 1 . PASC is clinically complex, comprising a spectrum of often nonspecific symptomatology and is placing increasing demands on health resources worldwide 2 , 3 . Although estimates vary, up to 30% of all individuals infected with SARS-CoV-2, and up to 80% of those discharged from hospital, report ongoing symptoms in the 3–6 months following virus exposure, including breathing difficulties, fatigue/malaise, muscle weakness, chest/throat pain, headache, abdominal symptoms, myalgia, cognitive symptoms and anxiety/depression 3 , 4 , 5 . Although most frequent following severe disease, nonhospitalized individuals infected with SARS-CoV-2 also show an increased likelihood of poor health outcomes at 6 months post infection 2 .

PASC has been associated with features of acute COVID-19 (refs. 6 , 7 , 8 )—including the efficacy of the innate antiviral response—implying that poor viral control perpetuating ongoing inflammation, acute respiratory distress and end-organ damage may predispose individuals to ongoing symptomatology. Various predictors of PASC have been suggested, including female sex 7 , 9 , 10 , 11 , 12 , increased viral load at presentation 10 , lower peak SARS-CoV-2 antibody titers 6 , 7 , increased duration of hospital stay 13 and reactivation of latent Epstein–Barr virus infection 14 , 15 . Immune changes persisting for months following COVID-19 have also been detected 16 , 17 , 18 , 19 , although it is unclear whether these drive PASC or are independently reflective of acute disease severity. Immune abnormalities persist for up to 2 months from COVID-19 symptom onset in patients who require intensive care admission 20 , yet longitudinal studies assessing biological and clinical features of COVID-19, with dense repeated sampling from the same individuals spanning acute infection to long-term recovery, are lacking. Such datasets are required to investigate prolonged symptoms in the context of the full disease trajectory and identify early correlates of poor outcome.

Here we present an extended longitudinal characterization of 214 SARS-CoV-2-infected individuals, from asymptomatic to requiring ventilation, who were followed for up to one year from the first SARS-CoV-2-positive swab or symptom onset. Combined analysis of longitudinal immunological, hematological, transcriptomic and clinical data indicated inflammation-driven iron dysregulation that persisted beyond 2 weeks in patients who were hospitalized with COVID-19 and which had apparent physiological repercussions for erythropoiesis and iron homeostasis months after infection. With integrated assessment of patient-reported PASC symptoms, we show that this signature of slow-resolving inflammation, iron dysregulation and ineffective compensatory stress erythropoiesis was a strong early correlate of PASC more than 3 months later.

Immune-cell abnormalities persist following COVID-19

A total of 214 individuals PCR-positive for SARS-CoV-2 (enrolled before August 2020) were classified into five groups on the basis of peak COVID-19 severity as follows (M, male; F, female; age, median (range)): asymptomatic (group A; n  = 18 (3 M and 15 F); 28 (20–71) yr), mild symptomatic (group B; n  = 40 (9 M and 31 F); 31 (19–58) yr), moderate without supplemental oxygen requirement (group C; n  = 48 (25 M and 23 F); 59.5 (17–87) yr), moderate with supplemental oxygen given as maximal respiratory support (group D; n  = 39 (25 M and 14 F); 65 (35–87) yr) and severe with assisted ventilation (group E; n  = 69 (52 M and 17 F); 56 (25–89) yr; Fig. 1a–c and Supplementary Table 1 ). All individuals in groups C–E were hospitalized and those in groups A and B were not. Matched blood, plasma and serum samples were collected at various time points up to day 352 post symptom onset or post the first positive swab for group A (hereafter post onset) and analyzed in batches that grouped samples collected in six discrete time windows (days 0–14, 15–30, 31–90, 91–180 and 181–360 post onset; Supplementary Fig. 1 ). Healthy controls (HCs) with negative SARS-CoV-2 serology ( n  = 45 (25 M and 20 F); 40 (19–73) yr) and historical HC samples that had been stored before November 2019 ( n   = 28 (14 M and 14 F); 62 (22–80) yr) were used as a reference in severity group analyses (Fig. 1a–c ). The patients in groups C–E were older than those in the A, B and HC groups, and more frequently men.

a , Distribution of patient sampling across five COVID-19 severity groups over 1 yr post first SARS-CoV-2-positive swab (group A) or symptom onset (groups B–E). Group A, mild asymptomatic, n  = 18 (3 M and 15 F), WHO clinical progression score = 1; group B, mild symptomatic, n  = 40 (9 M and 31 F), WHO score = 2–3; group C, moderate without supplemental oxygen requirement, n  = 48 (25 M and 23 F), WHO score = 4; group D, moderate with supplemental oxygen given as maximal respiratory support, n  = 39 (25 M and 14 F), WHO score = 5); and group E, severe with assisted ventilation, n  = 69 (52 M and 17 F), WHO score = 6–10. Repeat samples totaled 73, 148, 132, 114 and 288 across groups A–E, respectively. HCs were sampled at baseline day 0 ( n  = 60, 34 M and 26 F). Each point represents a time point of blood collection; samples from patients who later died are rimmed in black. Vertical dashed lines, the span of time windows used in all analyses (that is, days 0–14, 15–30, 31–90, 91–180, 181–270 and 271–360 post onset). The time range of follow-up questionnaire submission (Q1, 3–5 months and Q2, 9–10 months) is indicated (top). b , c , Distribution of age ( b ) and sex ( c ) across groups A–E and the HCs defined as in a . The demographics for the deceased patients alone are shown (bottom). d , Absolute cell count differences (fold change) between the patients in severity groups A–E and HCs during the analyzed time windows. e , f , Number of pDCs ( e ) and the ratio of activated/naive CD8 + T cells ( f ) in severity groups A–E and HCs. The gray band represents the interquartile range (IQR) of the HCs; the y axis is shown as a logarithm base ten scale. Box plots show the minimum value, 25th percentile, median, 75th percentile, maximum value and outliers beyond 1.5× the IQR. d – f , * P  < 0.05, ** P  < 0.005 and *** P  < 0.0005; significance of group effect (per COVID-19 severity group, per time window relative to the HCs) as calculated by linear regression of the log 2 -transformed counts (or ratio) with correction for age and sex; no multiple testing correction was applied. DP, deceased patient.

To characterize immunological recovery from COVID-19, changes in the absolute number of isolated peripheral blood mononuclear cell (PBMC) subpopulations were assessed for groups A–E relative to the HCs for each time window, with age and sex correction (Fig. 1d and Supplementary Fig. 2 ). The early T and B cell lymphopenia detected in groups C–E at day 0–14 post onset was resolved by day 15–30 in group C but delayed in groups D and E (Fig. 1d ). Absolute numbers of mucosal-associated invariant T (MAIT), Vγ9Vδ2 hi T and plasmacytoid dendritic (pDCs) cells in groups D and E remained low beyond day 90 (Fig. 1e and Supplementary Fig. 2 ). High CD27 + CD38 hi plasmablast counts were detected up to and beyond day 90 in all groups (Fig. 1d ). Elevated counts of central memory CD45RA lo CCR7 + CD8 + T cells (CD8 + T CM cells) were most notable in groups A and B, persisting to day 180 and day 90, respectively (Fig. 1d ). An increased ratio of activated/naive CD4 + T cells and CD8 + T cells remained pronounced in group E until day 360 (Fig. 1f ). Collectively, longitudinal immune-cell profiling indicated prolonged immunological disruption (most pronounced in groups C–E) following moderate–severe COVID-19.

Effect of inflammatory anemia on stress erythropoiesis post COVID-19

Inflammation and disrupted iron homeostasis occurs in hospitalized patients with COVID-19 (refs. 21 , 22 , 23 , 24 ). The levels of C-reactive protein (CRP) as well as cytokines such as interleukin (IL)-6, IL-10, IL-1ß and tumor-necrosis factor (TNF)-α, which were increased at day 0–14 in the serum of group C–E compared with HCs, resolved slowly over a period of months to a year, with elevated serum concentrations of some inflammatory cytokines, most markedly IL-6, still detectable at day 271–360 post onset (Fig. 2a and Supplementary Fig. 3 ). The iron-regulating hormone hepcidin (induced by IL-6) 25 blocks the release of iron from cells, particularly from erythrophagocytic macrophages, through direct binding and degradation of the cellular iron exporter ferroportin 26 . Hepcidin was elevated in the serum of groups C–E at day 0–14 compared with the HCs (Fig. 2a ), and elevated serum concentrations of the iron storage protein ferritin were seen up to days 30, 90 and 180 for groups C, D and E, respectively (Fig. 2a ), suggesting ongoing inflammation and increased cellular iron retention. In contrast, the levels of iron, the iron transport protein transferrin and transferrin iron saturation (TSAT; the ratio of serum iron to the blood’s total iron binding capacity) were markedly reduced in the serum of groups C–E at day 0–14 compared with HCs, and serum iron and TSAT remained significantly lower in group E at day 181–270 post onset (Fig. 2a,b and Supplementary Fig. 3 ). There was little evidence of systemic inflammation or associated disruptions to the iron levels of groups A and B (Fig. 2a ).

a , Fold change in median serum inflammatory, iron and erythroid cell parameters between patients with COVID-19 in severity groups A–E and HCs or group A and B samples taken at day >90 for ferritin in the absence of HC measures. Fold changes are shown for all time windows. Gray boxes in a correspond to the data shown in b – e . b – e , Serum iron ( b ), hemoglobin ( c ), reticulocyte count ( d ) and reticulocyte hemoglobin ( e ) in patients from groups A–E as in a . The gray band represents the IQR of the HCs. Data points from patients who later died are rimmed in black. Box plots show the minimum value, 25th percentile, median, 75th percentile, maximum value and outliers beyond 1.5× the IQR. a – e , The significance of group effect (per COVID-19 severity group, per time window relative to HCs) was calculated by linear regression of log 2 -transformed measures with correction for age and sex; no multiple testing correction was applied. d , e , Patient-level data plotted against time as a continuous variable (right), with quadratic regression lines fit for each severity group. f , Selection of the top significantly enriched HALLMARK gene sets from GSEA run on the log 2 -transformed fold change ranked gene lists from comparisons of groups A–E with HCs at each time window. Heat map of false discovery rate (FDR)-adjusted P values ( P FDR ) from the GSEA, with gene sets that were up- or downregulated colored in red and blue, respectively; NS, not significant. g , Polynomial splines showing changes in the heme-metabolism score (PC1 from a PCA of heme-metabolism gene-set genes across all sampling time points) over time for groups A–E. The gray band represents the IQR of the HCs. h , Correlation between the heme-metabolism score and reticulocyte count of groups C–E (scaled residuals following correction for time post symptom onset) at day 31–90. R , Spearman’s correlation coefficient. b – e , g , h ,The colour key in b applies to all panels. hsCRP, high-sensitivity C-reactive protein; OXPHOS, oxidative phosphorylation; HGB, hemoglobin; retic., reticulocyte. * P  < 0.05, ** P  < 0.005 and *** P  < 0.0005.

Low iron in combination with increased ferritin and hepcidin in the serum is a characteristic of inflammatory anemia 27 , 28 , which is associated with dysregulated iron trafficking and disrupted erythropoiesis in the context of systemic inflammation. Groups C and D showed declining concentrations of hemoglobin in the blood relative to HCs for the first 30 days post onset, with hemoglobin levels continuing to decline to day 30–90 for group E (Fig. 2a,c ). In addition, the serum levels of the erythropoiesis stimulating hormone erythropoietin (EPO), which is induced by low blood oxygen levels but suppressed by inflammation 29 , showed a delayed increase from HC levels, with concentrations peaking at day 15–30 in group E and day 31–90 in groups C and D (Fig. 2a and Supplementary Fig. 3 ). The four patients in group E who died between day 91 and 180 had the lowest hemoglobin concentrations of all 24 patients profiled at this time (Fig. 2c ; mean = 81.5 g l −1 ), which suggests an association between unresolved anemia and COVID-19 severity. Collectively, iron starvation of erythroid cells following inflammatory iron sequestration may compromise the homeostatic response to anemia in moderate–severe COVID-19.

To investigate the effect of altered iron availability on long-term erythropoiesis, we assessed several hematological parameters in groups A–E across days 0–14, 15–30, 31–90 and 90–180 post onset. Reticulocyte counts, which reflect the production of new erythrocytes, were low across all groups (significantly lower for groups B, D and E) at day 0–14 compared with HCs (Fig. 2a,d ). A subsequent steep increase in the reticulocyte count and immature reticulocyte fraction (IRF; the fraction of immature reticulocytes in total reticulocytes) resulted in a peak in reticulocyte counts above HC at day 31–90 in groups C, D and E (Fig. 2a,d ). Reticulocyte counts in groups A and B resolved HC levels by day 15–30. Total red blood cells remained depleted in group E up to day 91–180 (Fig. 2a,d and Supplementary Fig. 4 ). The reticulocyte hemoglobin and mean corpuscular hemoglobin concentration (the average hemoglobin concentration per volume of red blood) remained low in groups C–E at the time of peak reticulocyte production (day 31–90; Fig. 2a,e and Supplementary Fig. 4 ), suggesting defective stress erythropoiesis that proceeded in the absence of sufficient iron for hemoglobin production.

A gene-set enrichment analysis (GSEA) of genes that were differentially expressed between groups A–E and HCs showed HALLMARK genes linked to heme metabolism as the most strongly upregulated in the whole-blood transcriptome from groups C–E at day 31–90 (GSEA P  < 1 × 10 −43 ; Fig. 2f and Extended Data Fig. 1a ), consistent with delayed expansion of heme-producing reticulocytes. Reactive oxygen species (ROS), oxidative phosphorylation and hypoxia pathways, among others, were also significantly upregulated at this time (Fig. 2f and Extended Data Fig. 1a ). Genes encoding enzymes involved in heme biosynthesis, such as ALAS2 and FECH , were also significantly overexpressed in groups C–E at day 31–90 compared with HCs (Extended Data Fig. 1b ). Genes linked to interferon (IFN), IL-6–JAK–STAT3 and TNF-α signaling were strongly enriched in all groups at day 0–14 relative to HCs (Fig. 2f ), indicating that the upregulation of genes linked to heme metabolism occurred later than gene sets capturing the early inflammatory response. To correlate gene-set expression with hematological and immune variables, we used principal component analysis (PCA) of HALLMARK heme metabolism genes to generate a composite ‘heme metabolism score’ at each RNA-sequencing (RNA-seq) time point (Extended Data Fig. 2a ). When assessed over time as a continuous variable, the heme metabolism score increased in early disease, peaked at approximately day 30–50 before declining in groups B–E and remained stable in group A (Fig. 2g ). After adjustment for the day on which each sample was taken within each time window, the heme metabolism score at day 0–30 and day 31–90 in groups C–E combined was most strongly positively correlated with reticulocyte count (Fig. 2h ) and IRF (Extended Data Fig. 2b ) measured at the same time point, and negatively correlated with hemoglobin levels (Extended Data Fig. 2b ). Together, the pronounced late-stage heme metabolism signature observed at day 31–90 in the whole blood of patients from groups C–E coincided with an increase in iron-deprived reticulocytes following infection.

Prolonged changes to iron handling in patients with COVID-19

Iron is essential for cellular respiration and metabolism, yet accumulation of free cytosolic iron catalyzes the production of ROS and contributes to lipid membrane peroxidation and ferroptosis 30 , 31 . To investigate the consequences of altered cellular iron levels in COVID-19, we investigated the expression of genes from two publicly available gene sets in patient and HC whole-blood transcriptomes over discrete time windows. The first set included ‘IRE_HQ’ transcripts containing high-quality canonical iron-response elements (IREs) in their 3′ or 5′ untranslated region 32 and the second set included ‘iron-homeostasis’ transcripts encoding regulators of iron transport and uptake (such as TF and TFRC ), storage ( FTL, FTH1 and NCOA4 ) and antioxidant defense ( GPX4 , GCLM and GCLC ; based on the WikiPathways Ferroptosis gene set 33 ; Supplementary Tables 2 and 3 ). Iron-response proteins IRP1 and IRP2 are post-transcriptional modulators of iron-response genes that regulate cellular iron storage and flux through binding of IREs in target messenger RNA and promoting stabilization or degradation of transcripts 34 . The binding affinity of IRPs for IREs in target genes is dependent on the cellular concentration of iron. IRE_HQ genes showed clear polarization, with genes both significantly up and down regulated in groups C–E at day 0–14 (Fig. 3a and Extended Data Fig. 3a ), with most still differentially expressed in group E at day 30–90 (Supplementary Fig. 5 ), consistent with a response to altered cellular iron concentration 35 . The IRE-containing genes FTL1 and FTH1 (encoding ferritin), SCL40A1 (encoding the iron exporter ferroportin) and EPAS1 (encoding the hypoxia-inducible factor HIF-2α) were among those that were upregulated early in hospitalized patients (Fig. 3a and Supplementary Fig. 5 ), consistent with known responses to high intracellular iron 35 . As IRP1 and IRP2 regulate IRE-containing genes at the post-transcriptional level 35 , we validated the observed changes in mRNA expression in PBMCs from 21 day 0–14 COVID-19 samples using mass spectrometry (groups A + B, n  = 7; group C, n  = 5; groups D + E, n  = 9) 36 . Protein mass spectrometry analysis indicated bidirectional regulation of proteins encoded by IRE-containing genes, which was most distinct in groups D and E combined (Extended Data Fig. 3b,c ), suggesting that the differential regulation of iron-response genes (probably mediated by IRPs) was detectable at both the transcript and protein level in moderate–severe COVID-19.

a , Distribution of the log 2 -transformed fold change (FC) values across 324 measured genes with high-quality conserved IREs in their 3′ or 5′ untranslated region derived from the whole-blood transcriptome comparison of COVID-19 severity groups A–E at day 0–14 and HCs. Four genes of interest are annotated. b , Distribution of the log 2 (FC) across 60 measured genes in the iron-homeostasis gene set at day 0–14 (top) and heat map of gene-level detail for groups A–E versus HCs at day 0–14 (bottom). * P  < 0.05, P FDR values from GSEA. c , Schematic of iron-homeostasis pathway (KEGG has04216) with genes colored according to the log 2 (FC) in group E at day 0–14. Genes corresponding to those shown in the heat map in b are annotated in blue text. d , Polynomial splines showing change in iron-homeostasis scores (PC1 from PCA of iron-homeostasis gene-set genes across all sampling time points for groups A–E). The gray band represents the IQR of the HCs. e , Spearman correlation between iron-homeostasis score and serum iron in groups C–E (scaled residuals following correction for time) at day 0–14, with points colored by severity group.

Overexpression of iron-homeostasis genes relative to HCs was observed up to day 90–180 in group C, day 30–90 in group D and day 180–270 in group E (Fig. 3b and Extended Data Fig. 3d ). The upregulated genes reflected cellular responses consistent with both iron overload and iron deprivation, probably capturing signatures from different blood-cell subsets. Overexpression of genes encoding for constituents of the glutathione peroxidase (GPX4) pathway—including SLC7A11 , SLC3A2 , GCLC , GCLM and GPX4 (Fig. 3b,c and Extended Data Fig. 3e ), which are involved in defenses against ROS-mediated lipid peroxidation—reflected iron overload. In addition, NFE2L2 (encoding the transcription factor NRF2, a regulator of antioxidant responses) was overexpressed up to day 30–90 in group E (Extended Data Fig. 3f ). Changes consistent with cellular iron deprivation were also detectable. Groups C–E showed significant upregulation of TFRC (encoding the receptor for transferrin-bound iron) and NCOA4 , which is involved in ferritin degradation and release of iron stores during instances of increased iron demand (Extended Data Fig. 3e ) The fold change in expression of iron-homeostasis genes at day 0–14 in group E relative to HCs was projected onto the relevant KEGG hsa04216 pathway (Fig. 3c ). We used a composite ‘iron-homeostasis score’ to assess changes in iron-homeostasis gene expression across groups A–E compared with HCs over time as a continuous variable (Extended Data Fig. 2a ). Prolonged shifts in the transcriptional response to cellular iron levels and demand were observed in groups C–E, with a peak at day 0–14, but remained detectable for months following symptom onset (Fig. 3d ). Iron-homeostasis scores correlated strongly with inflammatory parameters, including CRP and IL-6, and inversely correlated with serum iron across corresponding time windows in groups C–E combined (Fig. 3e and Extended Data Fig. 2b ). Collectively, whole-blood transcriptional analysis identified gene expression signatures consistent with cellular responses to altered iron status that were slow to resolve following moderate–severe COVID-19.

Cellular deconvolution of iron signatures with multimodal single-cell data

To elucidate the cell-type origin of the whole-blood transcriptional signatures, we assessed the expression of the iron-homeostasis and IRE gene sets, alongside the HALLMARK heme-metabolism signature reflecting reticulocytosis in moderate-severe COVID-19, in published PBMC cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) data 37 from a subset of patients infected with SARS-CoV-2 ( n  = 36, groups A–E combined, median 11 days post-onset) as well as from HCs ( n  = 11; Fig. 4a ). We used an additional gene set derived from the transcriptome profiling of CaCo-2 cell lines (an in vitro model of intestinal absorptive cells) cultured in iron-free media 38 as a signature for iron starvation (Supplementary Table 4 ). Three distinct patterns of cell type-specific gene expression were identified (Fig. 4b ). First, the heme metabolism signature was nearly exclusively derived from a small cluster of CD71 hi reticulocytes (Fig. 4b and Extended Data Fig. 4a,b ), consistent with the expected tight coupling of this signature to reticulocyte counts. Second, iron homeostasis pathway genes and the IRE-containing genes upregulated in group E were preferentially expressed in myeloid-derived cells (Fig. 4b and Extended Data Fig. 4a,b ). These signatures had the highest relative expression in cell clusters annotated as nonclassical CD16 + monocytes, and several classical CD14 + monocyte subsets and dendritic cells (Fig. 4b ). Finally, the low-iron signature, which reflected iron starvation in vitro 38 , was preferentially expressed in proliferating CD4 + and CD8 + lymphocytes (Fig. 4b ), suggesting increased iron demand in proliferating lymphocytes around day 11 post onset, a time point coinciding with limited serum iron availability.

a , Uniform manifold approximation and projection (UMAP) of CITE-seq data from 36 patients with COVID-19 and 11 HCs, with cells labeled based on previously published cell-type annotations 37 . The UMAP was generated using mRNA expression data and is shown for visualization of cell clusters only. ILC, innate lymphoid cell. b , Average expression of heme metabolism and iron-related signature genes aggregated at the sample level within each cell cluster (COVID-19 and HC samples were combined). Cell types with the highest 80th percentile of average signature expression relative to other cell types, across individuals, are shown, with all other clusters merged into the population ‘other’. c , Comparison of cell frequencies of myeloid populations as a fraction of the total sequenced cells per individual in patients with COVID-19 (groups A–E combined) and HCs (left). d , Differences in the Spearman correlation of normalized CD71 protein expression, across cell clusters, with the surface proteins shown, in patients with COVID-19 (groups A–E combined) and HCs. Top proteins with the greatest difference in correlation (>0.23) are shown. e , Differences in normalized CD71 expression within subsets of HCs and patients with COVID-19, with data analyzed at the sample level, aggregated within each cluster per individual (left). c , d , Comparison of the COVID-19 and HC samples using −log 10 -transformed P values from a two-sided Wilcoxon rank test (right). b , c , e , Box plots show the minimum value, 25th percentile, median, 75th percentile, maximum value and outliers beyond 1.5× the IQR. DC, dendritic cell; mono., monocyte; mem., memory; prolif., proliferating; retic., reticulocyte.

The preferential expression of iron-homeostasis genes in monocytes is consistent with the known erythrophagocytic and iron-acquiring capabilities of these cells 39 . The size of CD16 + and CD14 + monocyte clusters were smaller in COVID-19 than in HC samples (Fig. 4c ), consistent with iron scavenging and trafficking to tissues. A repeat analysis of an independent, previously published single-cell COVID-19 dataset 40 indicated similar preferential expression of iron-homeostasis genes in monocyte clusters and reduced frequency of CD14 + classical and CD16 + nonclassical monocytes in COVID-19 samples compared with HCs (Extended Data Fig. 4c ). To evaluate the iron demand of various immune-cell subsets during an active viral infection, we analyzed the differential correlation between the expression of cell-surface markers and that of the transferrin receptor CD71 in patients with COVID-19 compared with HCs. CD71 expression was more tightly correlated with markers of innate immune cells (LILRB1, CD64, CD1d and CD1c) and markers of activation (SLC3A2, CD86 and ICAM-1) in the COVID-19 group than in HCs (Fig. 4d ), suggesting an increased demand for iron in concert with the activation of innate immune cells during a viral infection. CD71 expression was also elevated on CD16 + and CD14 + monocytes of patients with COVID-19 compared with HCs (Fig. 4e ). Thus, a multimodal single-cell analysis identified the cells contributing to signatures of defective iron homeostasis in the blood of patients with COVID-19 and suggested that iron sequestration in monocytes might contribute to the concurrent iron deprivation of proliferating CD4 + and CD8 + lymphocytes.

Early inflammatory iron dysregulation persists in PASC

To assess the outcome of prolonged iron dysregulation and disrupted erythropoiesis following SARS-CoV-2 infection on PASC, 102 patients in groups B–E (B, n  = 27; C, n  = 37; D, n  = 24; and E, n  = 14) completed follow-up questionnaires 3–5 months (questionnaire 1, Q1) and 9–10 months (questionnaire 2, Q2) post onset. The severity of seven persisting or new-onset symptoms were scored from zero (worst symptom severity) to five (no symptoms or full recovery; Supplementary Note and Methods ). Hierarchical clustering of scores allowed the classification of patients experiencing persisting symptoms (PS) or no PS (NPS) at Q1 and Q2 (Fig. 5a and Extended Data Fig. 5a,b ). Persisting symptoms were more frequent in groups C–E than group B, and of those reporting at Q1 and Q2, 65% had PS at both time points (Extended Data Fig. 5c,d ). There were no differences in sex or measured early viral titers between the symptom groups (Extended Data Fig. 5e,f ). The patients with PS were older than those with NPS; however, age did not differ between the PS and NPS groups when the patients were stratified by initial disease severity (Extended Data Fig. 5g and Supplementary Fig. 6 ), suggesting that age was indirectly associated with PASC only via an association with acute disease severity.

a , Grouping of patients with PS or NPS from hierarchical clustering of symptom severity scores (0, worst; 5, best) across seven symptom categories. The disease severity group (groups B–E) and total symptom score (summation across symptoms) are indicated above the heat map. The distribution of the responses to the follow-up questionnaires at Q1 and Q2 is shown (top). b , PLS-DA analysis of symptom groups from a study conducted on immune-cell counts, serum parameters and reticulocyte data collected between days 15 and 30. c , Variables driving differentiation of individuals with NPS and PS on PLS component 1, colored according to the group with highest mean. d , Unsupervised hierarchical clustering of patient data from day 15–30, using the 15 leading variables as in c . Patient symptom groups, severity groups and symptom severity scores are shown above the heat map. The cluster capturing most PS individuals is outlined by a black box. Missing data are shown in white in the heat map. e , Fold change (log 2 -transformed) in median serum inflammatory and iron parameters of individuals with PS compared with NPS at different time windows (left). The significance of the symptom group effect was calculated by linear regression of log 2 -transformed measures corrected for age; no multiple testing correction was applied. Patient-level data for the boxed parameters in more detail (right). The gray band represents the IQR of the HCs; the y axis is shown as a logarithm base ten scale. Measures taken at days 0–180 and 181–360 are annotated on the basis of the Q1 and Q2 symptom groups, respectively. f , Volcano plot showing genes that are differentially expressed, from differential gene expression analysis with age correction, between the PS (red) and NPS (green) groups at day 15–30 (left). Normalized expression for EPOR and EPAS1 (right); P values are from differential gene expression analysis before FDR correction. The gray band indicates the IQR of HC expression. CPM, counts per million reads. g , Significantly enriched HALLMARK and iron-homeostasis gene sets from GSEA run on the log 2 (FC) ranked gene list from a comparison of NPS and PS groups across time windows. P FDR values from GSEA are shown, with up- and downregulated gene sets in PS colored red and blue, respectively. a , e , f , Box plots show the minimum value, 25th percentile, median, 75th percentile, maximum value and outliers beyond 1.5× the IQR. ˙ P  < 0.1, * P  < 0.05, ** P  < 0.005 and NS, not significant; mDCs, myeloid DCs.

To identify biological variables that could discriminate PS and NPS groups at Q1, we conducted a partial least-squares discriminant analysis (PLS-DA) using previously analyzed immune-cell counts as well as serum and reticulocyte parameters collected within the sequential time windows. The PLS-DA discriminated PS versus NPS better at day 15–30 than during early disease (day 0–14) or at the time of Q1 responses (day 91–180; Fig. 5b and Supplementary Fig. 7 ). Variable selection identified 15 parameters measured at day 15–30 that predicted PS or NPS designation at Q1 with 72% accuracy (classification error rate, 28%; standard deviation, 2.5%; Fig. 5c ). Among these 15 variables, the mean CRP, IL-6, hepcidin and plasmablast counts were higher in PS, and the mean serum iron, transferrin and various immune-cell populations (including CD4 + T, CD8 + T, NK, regulatory T (T reg ) and dendritic cells) were lower in the PS group than in NPS at Q1 (Fig. 5c ). Unsupervised hierarchical clustering of data from 42 patients (12 PS and 30 NPS) at day 15–30 using only these 15 variables identified a subcluster of 13 individuals, nine of whom (group E, n  = 5; group D, n  = 2; group B, n  = 1; and group C, n  = 1) were classified as PS at Q1 (Fig. 5d ). This analysis suggested that a multivariate signature detectable at day 15–30 could discriminate the patients that experienced PASC at month 3–5 following SARS-CoV-2 infection, independent of hospitalization or oxygen therapy criteria.

Using a multivariate linear regression with age correction to test for an association between PASC symptom groups (NPS or PS) and biological measures, individuals in the Q1 PS group had significantly lower TSAT and serum iron compared with the NPS group at day 15–30 (Fig. 5e ). Reticulocyte counts were elevated in both the PS and NPS groups compared with HCs at day 31–90 (Supplementary Fig. 8 ), corresponding with the peak of the stress erythropoietic response, although they were significantly higher in PS compared with NPS (Fig. 5e ). This suggested that low iron availability, rather than delayed reticulocyte expansion, was a characteristic of stress erythropoietic responses in the PS group. Both CRP and IL-6 were elevated in the PS group compared with NPS at Q1 (day 91–180; Fig. 5e ). To further test that the observed differences in biological parameters between PS and NPS were not accounted for by the difference in age between the two groups, we performed pairwise symptom group comparisons in subsets of age-matched patients with COVID-19. This analysis indicated that serum iron, TSAT and hemoglobin levels were significantly lower at day 14–30, reticulocyte counts were significantly higher at day 30–90, and IL-6 and CRP were significantly elevated at day 90–180 in age-matched patients who reported PS at Q1 compared with the NPS group (Extended Data Fig. 6a,b ).

Severe COVID-19 and hospitalization has been linked with worse long-term outcome 8 , 41 . Because PASC was strongly associated with acute disease severity in our cohort, we repeated linear regression analyses including a correction for acute disease severity and following the exclusion of patients from group B to compare hospitalized PS and NPS groups matched for age, sex and severity. Both severity-corrected and severity-matched analyses indicated that serum iron and TSAT were significantly lower at day 14–30 in the PS group compared with NPS (Extended Data Fig. 6c,d ). The severity-matched analyses also indicated that CRP and IL-6 were significantly elevated in PS compared with NPS at day 90–180 (Extended Data Fig. 6c–f ). Although we did not have the statistical power to detect differences in symptom groups within peak disease severity groups (groups B–E), patients in group E with NPS trended toward more rapid recovery of low serum iron and resolution of systemic inflammation than patients in group E with PS (Supplementary Fig. 9 ). In addition, two of the three individuals with PS in group B had higher CRP at day 15–30 than the 20 individuals in group B with NPS (Supplementary Fig. 9 ). Together, these findings suggested that disruptions to iron handling that persisted beyond day 0–14, rather than the need for hospitalization or oxygen therapy, was linked to the risk of developing PASC months following acute disease.

Differential expression analysis using whole-blood transcriptomes identified 64 genes that were differentially expressed between the Q1 PS and NPS groups at day 15–30 post onset; these included EPOR (encoding the EPO receptor) and EPAS1 (HIF-2α), which were significantly upregulated in PS (Fig. 5f ). These genes are tightly regulated in response to low oxygen carriage, such as in anemia-induced hypoxia 42 . A GSEA analysis indicated that differences in gene expression across biological pathways were greater between the PS and NPS groups at day 15–30 than day 0–14. Individuals in the PS group had pronounced upregulation of heme metabolism and hypoxia pathways as well as ROS, IL-6–JAK–STAT3 signaling and iron homeostasis, among others, at this time (Fig. 5g and Supplementary Fig. 10 ). Genes linked to IFN signaling were downregulated in the PS group compared with NPS at day 15–30 (Fig. 5g ), suggesting a more transient early IFN response, as previously associated with severe disease 43 , 44 . Collectively, serum and transcriptional profiles from day 15–30 samples from patients with COVID-19 showed that persisting low iron in serum and delayed resolution of inflammation beyond 2 weeks following SARS-CoV-2 infection differentiated those with PS from those with NPS at 3–5 months, independent of the age and acute disease severity of the patients.

SARS-CoV-2 pathogenesis is well documented but the etiology of PASC remains unclear. Here we show that inflammation and disrupted iron homeostasis persisting beyond 2 weeks post COVID-19 onset best differentiated patients reporting PASC months later. We suggest unresolved inflammation affects long-term pathophysiology through disruptions to cellular iron mobilization and defective, iron-starved stress erythropoiesis that fails to correct the pronounced inflammatory anemia of early disease. Iron loading in monocytes and deprivation in lymphocytes was detected by CITE-seq and reflected in whole-blood transcriptional shifts in iron-response gene sets in patients with moderate–severe COVID-19 and in those later reporting PASC. Low iron availability, for erythropoiesis and cellular metabolism more broadly, potentially results in compromised antiviral immunity and low systemic oxygen carriage throughout and beyond acute infection. These abnormalities may help drive PASC and thus inform strategies for prevention or treatment of this complex phenomenon.

Hospitalized patients with COVID-19 often develop inflammatory anemia 21 , 22 , 45 , a common feature of chronic inflammatory conditions 28 , 46 , 47 . During inflammation, IL-6 stimulates the production of the hormone hepcidin by hepatocytes 25 , 48 , which induces the degradation of ferroprotein, the only known cellular iron exporter 26 . Reduced iron export drives iron accumulation in macrophages, which would otherwise recirculate iron liberated from phagocytosed senescent erythrocytes 49 . Sequestration of iron during infection helps defend against extracellular pathogens dependent on iron for survival 50 but also starves the erythroid compartment of iron for hemoglobin production, causing anemia 27 , 28 . We observed reduced serum iron, TSAT and hemoglobin concentrations as well as raised ferritin, hepcidin and IL-6 in COVID-19 severity groups C–E from day 0–14 post symptom onset, indicating inflammatory anemia in moderate–severe disease.

Oxygen transport requires O 2 coupling to the iron-containing heme molecules of hemoglobin, so modulation of blood oxygen levels necessitates control of iron availability. During hypoxia, the transcriptional regulator HIF-2α accelerates erythropoiesis via EPO 42 , 51 . Inflammation and low iron availability antagonize this process by suppressing EPO expression 29 , 52 , 53 , 54 . Despite experiencing hypoxia that warranted oxygen therapy, patients in groups D and E as well in group C, who did not receive oxygen supplementation, exhibited reduced reticulocyte production and delayed EPO induction in early disease. Following this, and consistent with a stress response to low blood oxygen levels, patients in groups C–E exhibited marked reticulocyte expansion, which peaked at 1–3 months post onset and was reflected in the overexpression of a heme metabolism signature in blood. In our cohort this phenotype was not only seen in severely ill, ventilated patients (group E) but also in hospitalized patients requiring only moderate or no oxygen therapy, and was pronounced in those subsequently reporting PASC. Stress erythropoiesis has been described in anemic mice 55 , 56 but is less well defined in humans 57 . Iron-starved reticulocytosis probably represents an inadequate physiological response to concurrent hypoxia, inflammatory iron restriction and anemia in moderate–severe COVID-19.

Iron availability is essential for cellular metabolism and regulates the function and proliferative capacity of leukocytes 58 , 59 , 60 . However, iron overload increases susceptibility to ROS-induced ferroptotic cell death 30 , 61 . Consistent with hepcidin-mediated iron redistribution, we observed transcriptional signatures of iron accumulation in circulating CD16 + classical and CD14 + nonclassical monocytes, potentially predisposing them to cellular dysfunction through ROS-mediated damage and contributing to tissue and organ pathology in patients with COVID-19. Iron-laden macrophages are detectable in post-mortem bone marrow samples of individuals following fatal COVID-19 (ref. 62 ), and ferroptosis in the ventricular myocardium or liver may cause end-organ damage and fatal disease 63 , 64 , 65 .

In contrast to signatures of high intracellular iron in monocytes, we saw evidence of iron starvation and increased CD71 surface expression in activated and proliferating leukocytes. Low iron availability compromises T cell effector function and humoral immunity 58 , 59 , 60 , NK cell activation 66 and neutrophil antimicrobial activity 59 , while hypoferremia during vaccination reduces central memory T cell responses and antigen-specific recall in mice 60 . Low serum iron at symptom presentation, coinciding with the induction of adaptive immunity, may impede the generation of SARS-CoV-2 cellular and humoral memory responses in patients with COVID-19. Even in normal iron conditions, hypoxia disrupts humoral immunity in mice by reducing B cell numbers and affinity maturation, defects similar to those observed in severe COVID-19 (ref. 67 ). Iron dysregulation and hypoxia may sustain a destructive cycle of impaired immune function, poor viral control and inflammation that contributes to tissue-specific and systemic manifestations of severe acute COVID-19, and potential disruption of long-term immune memory.

Many features of PASC may be driven, at least in part, by the impact of inflammatory iron dysregulation on erythropoiesis and blood oxygen carriage. We found that delayed resolution of inflammation and associated hypoferremia, rather than the magnitude of inflammatory perturbations during acute disease, best discriminated patients reporting persisting symptoms months post infection. Fatigue, pain and mood disorders have been linked to inflammatory anemia in chronic inflammatory conditions 68 , 69 and are common features of PASC 2 , 3 , 5 . Reduced oxygen delivery to muscles during exertion increases reliance on anaerobic glycolysis, elevating lactate production and leading to muscle fatigue and pain 70 . Low iron availability also impairs mitochondrial energy generation in skeletal muscle, decreasing physical endurance 71 . Iron deficiency and cerebral hypoxia have been linked to cognitive impairment and altered mood, and iron deficiency during childhood is a significant risk factor for poor cognitive performance 72 , 73 , 74 . Finally, low oxygen carriage may exacerbate tissue hypoxia and delay repair, and persisting iron dysregulation and anemia have been associated with more severe structural lung abnormalities following COVID-19 (ref. 75 ). Speculatively, the generally increased prevalence of iron deficiency in pre-menopausal women may contribute to the higher risk of PASC amongst this demographic 7 , 9 , 10 by enhancing the relative magnitude of infection-related iron redistribution against a baseline of lower iron stores.

Worse acute COVID-19 severity is a risk factor for PASC, and severe COVID-19 is predominantly seen in older males. Restricted access to uninfected population controls during the early pandemic resulted in suboptimal age and sex matching of HCs (recruited from healthcare workers) to patients with moderate–severe COVID-19 in this study, leading to differences in the demographic of PS and NPS groups. Although it is probable that acute and long-term symptom severity are to an extent causally linked, careful re-analysis of PASC symptom groups with age, sex and acute disease severity matching indicated that iron dysregulation at day 15–30 and raised inflammatory markers (IL-6 and CRP) at day 90–180 in the PS group were independent of these variables. Several clinical strategies may help mitigate the impact of early iron dysregulation on both acute COVID-19 severity and PASC. Vaccination, or selective antiviral or monoclonal therapy, may prevent sustained disruptions to iron homeostasis driven by severe uncontrolled inflammation. In those with worse disease, treatments directed at correcting abnormal iron distribution might also be considered. Reports that iron overload in the context of β-thalassemia protects from severe disease and mortality in individuals infected with SARS-CoV-2 (ref. 76 ) suggest a potential protective effect of increased iron availability, and preliminary reports on the impact of COVID-19 on patients enrolled in the IRONMAN clinical trial of intravenous ferric derisomaltose treatment for heart failure 77 show significantly reduced COVID-19-related severe adverse events in the iron-treated group (2.1%) than the usual care group (5.3%, P  = 0.007) 78 . This suggests a potential role for iron supplementation in COVID-19. Remobilization of endogenous iron stores can also increase iron availability. This may be achieved either directly through the use of hepcidin inhibitors 79 , which have shown efficacy in reversing inflammation-induced hypoferremia 80 , or through IL-6 inhibition. The IL-6R blocker tocilizumab, which reduces hepcidin generation, increases hemoglobin levels in patients with rheumatoid arthritis 81 , corrects inflammatory anemia in Castleman disease (associated with excessive IL-6 production) 82 and has been trialed as an anti-inflammatory agent in patients with COVID-19 (ref. 83 ). Thus, several potential therapies might be trialed to see if they reduce the incidence of PASC in patients with moderate–severe COVID-19.

It is unlikely that these observations are SARS-CoV-2 specific. Disruption of host iron homeostasis is a consequence of many viral infections, both through direct viral mechanisms of interference and as a consequence of the evoked inflammatory response 50 , 84 . Many infectious diseases—including Ebola 85 , 86 , influenza 87 and SARS 88 —elicit broadly similar post-acute sequelae, suggesting similar iron-redistribution strategies may be considered. This study has implicated disrupted iron homeostasis and iron-deprived stress erythropoiesis that persisted for more than 2 weeks from symptom onset as potential drivers of PASC. If confirmed, this immediately suggests several strategies that could be explored to prevent it.

Cohort recruitment and biological sample collection

Study ethics approval was obtained from the East of England—Cambridge Central Research Ethics Committee (‘NIHR BioResource’ REC ref. 17/EE/0025 and ‘Genetic variation AND Altered Leucocyte Function in health and disease—GANDALF’ REC ref. 08/H0308/176). All participants provided informed consent. We have previously published detailed information on the recruitment, sampling time line, clinical characteristics and demographics of 104 patients admitted to Addenbrooke’s Hospital, Royal Papworth Hospital (RPH) NHS Foundation Trust or Cambridge and Peterborough Foundation Trust who tested SARS-CoV-2 positive and 97 asymptomatic or symptomatic healthcare workers attending the Addenbrooke’s serology screening program between March and July 2020 20 . An additional 13 patients hospitalized with COVID-19 were recruited following discharge and provided blood samples for cellular and serum assays as well as RNA-seq from 130 days post symptom onset. Individuals who were PCR-positive for SARS-CoV-2 were classified into five groups based on peak disease severity: asymptomatic (group A; n  = 18, 3 M and 15 F; WHO clinical progression score = 1; age (median (range)), 28 (20–71) yr), mild symptomatic (group B; n  = 40 (9 M and 31 F); WHO score = 2–3; age, 31 (19–58) yr), moderate without supplemental oxygen requirement (group C; n  = 48 (25 M and 23 F); WHO score = 4; age, 59.5 (17–87) yr), moderate with supplemental oxygen given as maximal respiratory support using low-flow nasal prongs, face mask, Venturi mask or nonrebreather face mask (group D; n  = 39 (25 M and 14 F); WHO score = 5; age, 65 (35–87) yr) and severe with requirement for noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation (group E; n  = 69 (52 M and 17 F); WHO score = 6–10; age, 56 (25–89) yr). The mean time in hospital for patients in groups C, D and E with known date of discharge was 4.7 (IQR, 1–7), 11.2 (IQR, 6–16) and 52.6 d (IQR, 26.5–61.2), respectively. Twenty-four hospitalized patients (group E, n  = 21; group D, n  = 2 and group C, n  = 1) died over the course of the study period. An additional 45 HCs with confirmed negative SARS-CoV-2 serology (25 M and 20 F; age, 40 (19–73) yr) were used as reference in all clinical assays and statistical analyses; 28 additional historical healthy control samples stored previous to November 2019 (14 M and 14 F; age, 62 (22–80) yr) were included in the RNA-seq analyses (total n  = 60, 26 M and 45 F); age, 50 (19–80) yr). No statistical methods were used to pre-determine sample sizes, and recruitment was based on access to and availability of participants during national lockdown. Demographics of all COVID-19 patients and HC and the baseline clinical features of patients in groups A–E and HCs are included in Supplementary Table 1 .

Participant recall and sampling, beyond the study period extensively described previously 20 , occurred at approximately 3, 6 and 12 months following recruitment. At each time point, blood samples were drawn in sodium citrate, serum and PAXgene blood RNA tubes (BD Biosciences) and processed by members of the CITIID–NIHR COVID BioResource Collaboration, as previously described 20 . Serum aliquots were taken from approximately 9 ml of blood, spun at 800 g for 10 min. Peripheral blood mononuclear cells were isolated from approximately 27 ml blood collected in 10% sodium citrate tubes using Leucosep tubes (Greiner Bio-One) with Histopaque 1077 (Sigma) by centrifugation at 800 g for 15 min. The PBMC interface was collected, rinsed twice with autoMACS running buffer (Miltenyi Biotech) and cryopreserved in FBS with 10% dimethylsulfoxide previous to cell staining for immunophenotyping. The PAXgene blood RNA tubes were kept at room temperature for 2 h and then stored at −80 °C before RNA extraction. Patient sampling time lines were aligned by days post COVID-19 symptom onset, or the first positive swab in the case of asymptomatic participants, for all downstream analyses. To remove the possibility of confounding effects due to vaccination on late parameters, final time-point data from 25 participants who had received an mRNA-based COVID-19 vaccine before final sampling (within day 180–360 post onset) and a further ten for whom vaccine status could not be ascertained following the initiation of UK vaccine regimens in December 2020 were excluded.

Clinical data collection

Laboratory test results for hospital blood screening assays conducted during the preliminary study period (including serum cytokine, CRP, hemoglobin and ferritin concentrations), and repeated on recall samples and HCs, were extracted from Epic electronic health records (Addenbrooke’s Hospital) and MetaVision ICU (RPH). High-sensitivity CRP, hemoglobin and ferritin levels were measured by the NIHR Cambridge Biomedical Research Centre Core Biochemical Assay Laboratory using standard assays. The levels of the serum cytokines IL-6, IL-10, IL-1β, TNF-α and IFN-γ were measured using a High-sensitivity base kit HS cytokine A mag (product code LHSCM000, Bio-Techne R&D Systems) on a Luminex analyzer (Bio-Plex) by the Clinical Immunology Laboratory at Addenbrooke’s Hospital.

Follow-up questionnaire and long-term symptom groups

A follow-up questionnaire for the assessment of long-term outcomes following COVID-19 was based on a published tool developed by Cambridge University Hospitals for assessing rehabilitation need in patients with COVID-19 who had prolonged intensive-care-unit stays 89 . The original tool (the post-ICU presentation screen, PICUPS) was developed by a cross-disciplinary group of experienced clinicians and pilot tested in 26 hospitals across England. The modified questionnaire ( Supplementary Note 1 ) was administered to patients in groups B–E 3–5 months (Q1; n  = 107; mean 116 d post onset; IQR, 103–127 d post onset) and 9–10 months (Q2; n  = 59; mean 287 d post onset; IQR, 260–320 d post onset; Supplementary Fig. 1 ), and assessed a range of long-term self-reported outcomes. The participants were asked to report only on symptoms arising or worsening in severity following SARS-CoV-2 exposure. Only responses to questions requiring symptom severity scoring on a numerical scale from zero (worst) to five (best), as opposed to yes–no or descriptive responses, were included in the symptom group classification. Participant scores across seven symptom categories (fatigue, dyspnea, cough, pain, cognition and memory, new neurology and muscle weakness) were used to classify individuals into PS or NPS symptom groups at each questionnaire time point, as detailed below.

Questionnaire responses across both Q1 and Q2 were clustered using hclust in R. Two distinct clusters of questionnaire responses were defined using cutree, clearly distinguishing participants reporting PS or NPS at long-term follow-up. Biological samples collected before day 180 were analyzed based on the symptom group derived from the Q1 responses, those collected after day 180 were analyzed based on the symptom group derived from the Q2 responses. After exclusion of data from individuals for whom reporting took place after SARS-CoV-2 vaccination (or with unknown vaccination status), n  = 97 Q1 responses (26, 37, 22 and 12 from groups B, C, D and E, respectively) and n  = 26 Q2 responses (1, 9, 7 and 9 from groups B, C, D and E, respectively) were linked to previous sampling time points for downstream analysis.

Serum iron, hepcidin and EPO assays

Quantification of serum iron, total iron binding capacity (TIBC), transferrin, hepcidin and EPO was conducted by the NIHR Cambridge Biomedical Centre Core Biochemistry Assay Laboratory at Addenbrooke’s Hospital. Serum iron was measured using the Siemens Healthineers Dimension EXL iron assay (product code DF85) through absorbance-based detection of ferrous iron–Ferene complexes. Transferrin levels were quantified using a Siemens Healthineers Dimension EXL transferrin assay (product code DF103), a turbidimetric assay involving the formation of immune complexes between transferrin and antitransferrin. A Siemens Healthineers Dimension EXL IBCT assay (product code DF84) was used to determine TIBC. This is a colorimetric assay involving the addition of excess iron to saturate transferrin-iron binding sites, with excess unbound iron incorporated into ferrous iron–Ferene complexes and photometrically quantified as described above. Acidification of the reaction releases transferrin-bound iron for further incorporation into ferrous iron–Ferene complexes, resulting in increased absorbance in proportion to the concentration of transferrin-bound iron and thus TIBC. All assays were automated on a Siemens Dimension EXL analyzer. Transferrin saturation was calculated as: TSAT = (serum iron / TIBC) × 100.

Serum hepcidin levels were measured using a Bio-Techne R&D Systems human hepcidin Quantikine ELISA kit (product code DHP250), a quantitative sandwich ELISA method using an antihuman hepcidin monoclonal capture antibody and detection antibody, the latter conjugated to horseradish peroxidase. The enzyme oxidizes an added chromogen for photometric detection of a colored complex. Serum EPO was measured in a similar fashion using a Bio-Techne R&D Systems human erythropoietin Quantikine IVD ELISA kit (product code DEP00); the analyte was captured using monoclonal mouse anti-EPO and detected using a polyclonal rabbit anti-EPO conjugated to horseradish peroxidase.

Reticulocyte counts

Reticulocyte counts, IRF fractions, reticulocyte hemoglobin content and mean corpuscular hemoglobin concentrations were measured on blood samples collected between day 0 and 180 using a Sysmex XN-1000 hematology analyzer as per the manufacturer’s instructions.

Flow immunophenotyping

Flow immunophenotyping was performed with five florescent antibody panels, staining approximately 1 × 10 6 PBMCs, using a five-laser BD Symphony X-50 flow cytometer. Sample population gating was performed in FlowJo v10.2. The antibody panels and gating schema have been previously described in detail 20 . BD TruCount tubes (product code 340334, BD Biosciences) were used as per the manufacturer’s instructions for direct enumeration of T, B and NK cells. Enumerated parent populations were used to calculate the absolute counts (cells ml −1 ) of gated daughter populations.

Whole-blood RNA-seq

Extraction of whole-blood RNA stored in PAXgene blood RNA tubes (product number 762165, BD Biosciences) was performed using a PAXgene blood RNA kit (product number 762164; PreAnalytiX, Qiagen) as per the manufacturer’s protocol. A SMARTer stranded total RNA-seq v2–pico input mammalian kit (product number 634413, Takara) was used as specified by the manufacturer to prepare RNA-seq libraries using 10 ng RNA as the input. The libraries were sequenced using 75-bp paired-end chemistry on a HiSeq4000 instrument (Illumina). The sequencing read quality was assessed using FastQC v0.11.8 (Babraham Bioinformatics), with trimming of SMARTer adapters and poor-quality terminal bases (Phred score threshold < 24) with Trim Galore v0.6.4 (Babraham Bioinformatics). Ribosomal RNA contamination was removed using BBSplit (BBMap v38.67) and clean reads were aligned to the human reference genome GRCh38 using HISAT2 v2.1.0. Alignment.bam files were merged and read count matrix generated using the function featureCounts from the R package Rsubread (v2.0.1). Count data were stored in a DGEList object with accompanying gene annotations and patient metadata for downstream handling (EdgeR v3.28.1). Nineteen samples with fewer than 2,000,000 assigned reads, and one sample with an abnormal read distribution were excluded. Genes with >1 count per million reads in >5% of samples were retained, and genes on the Y chromosome and the X-chromosome inactivation factor XIST were excluded, leaving a total of 22,354 genes with expression counts across 610 serial COVID-19 and control whole-blood samples. Normalization for library size was performed using the calcNormFactors function from EdgeR (v3.28.1). The function voom (limma v3.42.2) was applied to the count matrix to estimate the mean-variance relationship, enabling adjustment for heteroscedasticity. Batch variation identifiable across seven sequential RNA extraction batches was corrected for using the empiricalBayesLM function from the R package WGCNA (v1.69), using transcriptomes from HCs as well as group A and B samples taken beyond day 60 as references. Residual batch variation was corrected for by the inclusion of a batch covariate in the statistical model for differential gene expression analysis as described in the ‘Statistical analysis’ section. Genes were annotated using the R package AnnotationDbi (v1.48.0).

Mass spectrometry

Previously published PBMC mass spectrometry data for seven HCs and 21 patients with COVID-19 during early disease (day 0–14), included in a published proteomic analysis of the same disease cohort, were used. All methods are detailed in the associated text 36 .

The CITE-seq data were downloaded from the public portal https://covid19cellatlas.org/ . Cell metadata and raw unique molecular identifier counts for mRNA and antibody-derived tags (surface protein counts) were extracted and analyzed using R as described in the ‘Statistical analysis’ section. The expression distribution of lineage-defining surface proteins from cell clusters of interest confirmed the validity of subset annotations (Extended Data Fig. 4b ).

Statistical analysis

All statistical analyses were conducted in R v3.6.0 (ref. 90 ) using custom scripts and publicly available analysis packages. Longitudinal patient data for all biological and clinical measures were analyzed within severity (A–E) or persistent symptom (PS/NPS) groups, within sequential time windows spanning days 0–14, 14–30, 30–90, 90–180, 180–270 and 270–360 post COVID-19 onset. Due to low sample numbers, absolute cell counts derived from samples collected during day 180–360 were analyzed together in one window. Any severity-time window grouping containing two or fewer samples was excluded from analysis. For all severity group analyses, SARS-CoV-2-negative or historically collected HCs (RNA-seq only) were used as the reference comparison group throughout. Measured variables from individuals who went on to report PS were compared with those who went on to report NPS at each sampling time point. Hospital assays for ferritin concentrations were not performed on HC serum, so data collected for group A and B samples taken after day 90 were used as a representative ‘healthy’ baseline for these measures. For patients with repeated measures collected within a given time window, only the earliest sampling point was retained, except for analyses treating time as a continuous variable. Clinical variables (serum cytokines, inflammatory markers, iron and reticulocyte parameters, and absolute cell counts) were normalized by log 2 -transformation and COVID-19 severity group effects were tested using multivariate linear regression with correction for age (treated as a continuous integer value) and sex as covariates. The PASC symptom group effects were tested with age correction only as NPS and PS groups were sex matched at both questionnaire time points.

The validity of using age as a linear covariate for age-bias correction was tested by assessing the nature of age associations with clinical and cellular parameters in HCs and COVID-19 severity group samples taken beyond day 180 ( Supplementary Methods ). Only 13—including IL-6, IL-10, IRF, CD4 T cells (naive and activated, and naive:activated ratio), CD8 T cells (absolute counts, naive and activated:naive ratio), γδ T cells (total, Vγ9 + Vδ2 hi and Vγ9 + Vδ2 lo ) and MAIT cells—of the 47 measured parameters showed evidence of an association with age. For all these parameters, age effects could be effectively modeled using a linear covariate in HCs and patients with COVID-19. Differences detected between the PS and NPS groups (which also varied in age) were confirmed by a Wilcoxon test in various matched subsamples of the cohort, including age-matched participants, and age and acute disease severity-matched participants (with exclusion of group B patients, overrepresented in the NPS group, from analyses).

Whole-blood differential gene expression analysis between each severity group–time window comparison and HCs (or symptom group comparison) was performed using the lmFit function from the package limma 91 , applied to weighted linear models using voom 92 , adjusting for age, sex and RNA extraction batch using the design formula model.matrix( ∼ 0 + group + age + sex + extractbatch).

Intra-patient correlations were modeled using duplicateCorrelation to account for repeated sampling, with the patient ID used as a blocking factor. Test statistics for each gene expression comparison were regularized using the empirical Bayes method (eBayes in limma) with P values adjusted for multiple testing using the FDR. Genes with an absolute log 2 (fold change) ≥ 0.5 and P FDR  < 0.1 were considered significantly differentially expressed. A GSEA analysis was performed using the limma function camera 93 with HALLMARK and WP_FERROPTOSIS (here ‘iron homeostasis’) gene sets from the MSigDB database 94 or curated gene lists from published transcriptome analyses (IRE_HQ) 32 . Gene-set scores for heme metabolism and iron-homeostasis gene sets were derived using a PCA analysis of gene-set gene expression counts across all sampling time points. PC1 was used to capture variation in gene-set expression across samples as a continuous variable and modeled within each severity group using polynomial splines. Spearman correlations between gene-set scores and biological measures were computed within each analysis time window, using residuals extracted from the regression of each variable with days post onset to first correct for a possible confounding effect of time. The use of raw data or extracted residuals had minimal effect on correlation outcomes.

The CITE-seq UMAP plot shown for visualization purposes was calculated using 50 principal components based on variable mRNA defined using Seurat 95 with the method ‘vst’ in the FindVariableGenes function. The UMAP R package was used to calculate UMAP embeddings using the hyperparameters n neighbors = 40, spread = 0.5, minimum distance = 0.4 and random state = 42. Raw protein antibody-derived-tag counts were normalized and denoised using the dsb function ModelNegativeADTnorm 96 to remove rescale data to define the background signal of each protein and to remove cell-to-cell technical variations using per cell models and isotype controls. The function arguments were denoise.counts = TRUE, use.isotype.control = TRUE, pseudocount.use = 1 and quantile.clipping = TRUE. The dsb-normalized data were used in downstream analyses. To analyze the relative expression of each signature, raw UMI RNA counts were aggregated using the average expression per individual of each gene, and each gene signature was further aggregated as the mean of the genes in the signature per individual for each cell type. Cell types were defined using the author’s published annotations. The 80th percentile of median sample level expression across all cell types are highlighted as defining the main source of the signature, with other cell types merged into the ‘other’ population. Cell frequencies for each cluster were calculated for each sample as the number of cells divided by the total cells for that individual’s sample. Cell frequency comparisons between healthy donors and patients with COVID-19 were tested using a two-sided Wilcoxon rank test. Validation of the relative expression of iron-homeostasis genes across cell types, and monocyte cluster frequencies in the COVID-19 and HC groups, was performed using publicly available CITE-seq data from Schulte-Schrepping and colleagues 40 . The protein correlations across subsets were done on the median marker expression per subset. The subset of proteins with the highest difference in the Spearman’s correlation of CD71 with all other proteins in patients with COVID-19 compared with HCs are shown with a cutoff of a difference of 0.23. Analysis of protein correlation with iron homeostasis signatures within cell subsets was done using a linear model. Average dsb-normalized protein expression of each marker in monocytes was associated with the average expression of the iron homeostasis driver gene signature from the earliest time point for the COVID-19 samples. Protein coefficients were regularized toward the average effect using the eBayes function with limma.

Data collected across cellular, serum and reticulocyte variables, within each time window, were used for supervised PLS-DA analysis of symptom groups (PS versus NPS) using the plsda function from the package mixOmics (v6.10.9) 97 . The function tune.splsda was used to determine the variables that were most informative in symptom group discrimination within the day 14–30 time window, based on 30 permutations of fourfold cross-validation. Fifteen variables selected in ≥85% of permutations were used to cluster Q1 symptom groups based on patient data collected between days 14 and 30.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

Data availability

All datasets used in the generation of presented figures—including cell counts, serum measures, Sysmex hematology data, PAXGene whole-blood RNA-seq gene expression counts, patient metadata and PASC group assignments—can be downloaded from the Zenodo repository ( https://doi.org/10.5281/zenodo.10161238 ). Whole-blood RNA-seq data are available through the European Genome-Phenome Archive (EGA, ID: EGAS00001005332 ). CITE-seq processed data are available to download from Array Express using accession number E-MTAB-10026 . Published CITE-seq data from Schulte-Schrepping et al. 40 used for replication analysis are available through the EGA (ID: EGAS00001004571 ). HALLMARK and WP_FERROPTOSIS gene sets are accessible through the MSigDB database ( https://www.gsea-msigdb.org/gsea/msigdb/ ). The IRE gene set IRE_HQ is available as supplement in the article by Hin et al. 32 and the iron-starvation gene set was taken from Table 3 (‘genes upregulated in iron-free medium’) in the associated publication by Chicault and colleagues 38 . Gene sets are also available in Supplementary Tables 2 – 4 .

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Acknowledgements

The members of the Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute of Health Research (CITIID–NIHR COVID) BioResource are listed in the Supplementary Information and include the authors F.M., L.B., J.R.B., P.L. and K.G.C.S. We thank the NIHR BioResource volunteers for their participation, and acknowledge NIHR BioResource centers, NHS Trusts and staff for their contribution. We thank the National Institute for Health and Care Research, NHS Blood and Transplant, and Health Data Research UK as part of the Digital Innovation Hub Programme. The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or Department of Health and Social Care. We acknowledge the services provided by the University of Cambridge Stratified Medicine Core Laboratory, NIHR Cambridge Biomedical Research Centre (BRC) Core Biochemistry Assay Laboratory, NIHR Cambridge BRC Cell Phenotyping Hub, Cambridge Clinical Immunology Laboratory and University of Cambridge Department of Haematology for sample processing and biological data generation. We thank J. Stevens and L. Stefanucci from the Department of Haematology, University of Cambridge for their involvement in hematology data collection, and M. Potts and M. Weekes from the Department of Medicine, University of Cambridge for providing mass spectrometry data. We thank J. Frost from the Weatherall Institute of Molecular Medicine, University of Oxford MRC for his valuable contribution to the scientific interpretation of findings and manuscript structuring. We thank CVC Capital Partners, the Evelyn Trust (20/75), Addenbrooke’s Charitable Trust, Cambridge University Hospitals (12/20A), the NIHR Cambridge Biomedical Research Centre and the UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC) for their financial support. The BioResource was funded by awards from NIHR to the NIHR BioResource (grant numbers RG94028 and RG85445). K.G.C.S. was funded by a Wellcome Investigator Award (grant number 200871/Z/16/Z) and MRC Programme Grant (grant number MR/W018861/1). A.L.H. was funded by the EU H2020 project SYSCID Grant (grant number 733100).

Author information

Kenneth G. C. Smith

Present address: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

Present address: University of Melbourne, Melbourne, Victoria, Australia

A full list of members appears in the Supplementary Information.

Authors and Affiliations

Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK

Aimee L. Hanson, Matthew P. Mulè, Federica Mescia, Laura Bergamaschi, Victoria S. Pelly, Lorinda Turner, Prasanti Kotagiri, Christoph Hess, James A. Nathan, Paul A. Lyons & Kenneth G. C. Smith

Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK

Aimee L. Hanson, Matthew P. Mulè, Federica Mescia, Laura Bergamaschi, Victoria S. Pelly, Lorinda Turner, Prasanti Kotagiri, Christoph Hess, John R. Bradley, James A. Nathan, Paul A. Lyons & Kenneth G. C. Smith

NIH–Oxford–Cambridge Scholars Program, Department of Medicine, University of Cambridge, Cambridge, UK

Matthew P. Mulè

MRC Biostatistics Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK

• Hélène Ruffieux

British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK

Berthold Göttgens

NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge, UK

Christoph Hess

Department of Haematology, Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK

Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland

Nicholas Gleadall

Botnar Research Centre for Child Health (BRCCH), University of Basel and ETH Zurich, Basel, Switzerland

NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK

John R. Bradley

Department of Haematology, University of Cambridge, Cambridge, UK

MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

Hal Drakesmith

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Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration

• , Federica Mescia
• , Laura Bergamaschi
• , Lorinda Turner
• , Prasanti Kotagiri
• , Christoph Hess
• , Nicholas Gleadall
• , John R. Bradley
• , Paul A. Lyons
•  & Kenneth G. C. Smith

Contributions

Conceptualization: A.L.H., M.P.M., P.A.L., H.D. and K.G.C.S. Methodology: A.L.H., M.P.M., F.M., L.B., V.S.P., L.T., P.K., B.G. and H.D. Formal analysis: A.L.H. and M.P.M. Precursory analysis: L.B., V.S.P., L.T., P.K. and H.R. Data collection and curation: A.L.H., M.P.M., F.M., L.B., V.S.P., L.T., P.K. and N.G. Visualization: A.L.H. and M.P.M. Project administration: F.M. and L.B. Funding acquisition: B.G., J.R.B., P.A.L. and K.G.C.S. Supervision: P.A.L., H.D. and K.G.C.S. Writing (original text): A.L.H., M.P.M., P.A.L., H.D. and K.G.C.S. Writing (editing): A.L.H., M.P.M., H.R., C.H., J.A.N., P.A.L., H.D. and K.G.C.S. All authors contributed to the review of written text.

Corresponding author

Correspondence to Kenneth G. C. Smith .

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Extended data

Extended data fig. 1 whole blood hallmark gene-set enrichment and heme synthesis gene expression changes in covid-19 severity groups over time..

a , GSEA using MSigDB HALLMARK gene-sets run on the log 2 FC ranked gene lists for each COVID-19 severity group (A-E) and time-window comparison with HC. Shade represents FDR adjusted p-value, with gene sets up- or downregulated in COVID-19 colored in red or blue respectively. b , Log 2 fold-change of heme synthesis genes as taken from DGE analysis of COVID-19 severity groups and HC with age and sex correction, within time windows from symptom onset. FDR adjusted P-values from linear model fit: *p<0.1, **p<0.05, ***p<0.005.

Extended Data Fig. 2 Whole blood transcriptional scores correlated with measured serum and cellular parameters in COVID-19 severity groups over time.

a , PCA of COVID-19 patient and HC whole-blood transcriptomes across all sampling timepoints using genes in the HALLMARK heme metabolism gene-set (left), or iron-homeostasis gene-set (right). Points are colored according to mean expression across gene-set genes. PC1 scores are used to capture variation in gene set expression. b , Spearman correlation between HALLMARK heme metabolism score (top) or iron homeostasis score (bottom) and other measured biological variables in hospitalized patients (groups C–E combined) within discrete time windows. Variables are corrected for time by extracting residuals from linear regression with days post-onset prior to correlation. Asterisks represent significance at P<0.05 prior to FDR correction, points are colored according to strength of correlation.

Extended Data Fig. 3 Altered expression of iron-response gene-sets in COVID-19 severity groups over time.

a , Distribution of log 2 FC values across 324 measured genes with high-quality conserved iron-response elements (IRE_HQ) in their 3’ or 5’ UTR, derived from the whole-blood transcriptome comparison of COVID-19 severity groups (A-E) and HC over successive time windows. b , Distribution at day 0-14 from a, compared to corresponding distribution of log 2 FC values across 150 measured proteins in the IRE_HQ gene set, taken from matched samples within the same time window. Samples from patients in groups D and E, and groups A and B, were analyzed together relative to HC to improve sample sizes (n(HC)=7, n(A_B)=7, n(C)=5, n(D_E)=9). c , Correlation of log 2 FC values from the transcriptional comparison of group E patients and HC, and the protein level comparison of groups D+E and HC, at day 0-14. Pearson’s correlation coefficient and p-value shown. d , Distribution of log 2 FC values across 60 measured iron homeostasis genes, derived from the whole blood transcriptome comparison of COVID-19 severity groups and HC over successive time windows, GSEA p-value from gene-set enrichment analysis shown. e , Heat map showing log 2 FC of each gene in more detail. Significantly differentially expressed genes (P FDR <0.1, abs(log 2 FC) >0.5) are indicated with asterisks: * P FDR <0.1, ** P FDR <0.05, ***P FDR <0.005. f , Change in expression of master regulator of the antioxidant response, NFE2L2 (encoding NRF2), over time and across severity groups. Gray bar indicates IQR of the interquartile range of the HCs. FDR adjusted p-values from linear model fit: *p<0.1, **p<0.05, ***p<0.005. Boxplots show minimum, 25 th percentile, median, 75 th percentile and maximum, and outliers beyond 1.5 times the interquartile range.

Extended Data Fig. 4 Multimodal single cell analysis of iron-related gene signatures.

a , Heatmap of dsb normalized surface protein expression across cell subsets. Values are scaled for each protein across cell clusters. b , Distribution of cell surface protein expression in myeloid-derived cell subsets with highest expression of iron-related signatures, and reticulocytes. c , Data from Schulte-Schrepping et al. as validation of data shown in Fig. 4b,c . (top) Average expression of iron-homeostasis genes aggregated at the sample level within each cell cluster (COVID-19 patients and HC are combined). Cell types with the highest 80 th percentile of average signature expression relative to other cell types, across individuals, are shown, with all other clusters merged into the population “other”. (bottom) Cell frequency of myeloid populations as a fraction of the total sequenced cells per individual, compared between COVID-19 patients (orange) and HC (black). The right margin shows -log 10 of the p-value comparing COVID-19 and HC with a two-sided Wilcoxon rank test. Boxplots show minimum, 25 th percentile, median, 75 th percentile and maximum, and outliers beyond 1.5 times the interquartile range.

Extended Data Fig. 5 Classification and characteristics of PASC persisting symptom (PS) and no persisting symptom (NPS) groups.

a , Grouping of patients with persisting symptoms (PS) or no persisting symptoms (NPS) of COVID-19 from hierarchical clustering of symptom severity scores (0 worst to 5 best) across 7 symptom categories, reported at Q1 (month 3–5 post-onset) and Q2 (month 9–10 post-onset). Disease severity group (B-E) and total symptom score (summation across symptoms) is indicated above heatmap. b , Comparison of time from first COVID-19 symptom to follow-up at each questionnaire timepoint for PS and NPS groups. P-value derived from two-sided t -test comparison of group means. c , Flow of participants between symptom groups at two follow-up timepoints for 35 individuals providing responses for both. d , Proportion of NPS and PS individuals within disease severity groups (B-E) at both questionnaire timepoints. e , Distribution of sex, f , viral titer (as assessed by SARS-CoV-2 positive swab cycle threshold value) and g , age between PS and NPS groups at both follow-up time-points. P-values calculated by two-sided t -test. Boxplots show minimum, 25 th percentile, median, 75 th percentile and maximum, and outliers beyond 1.5 times the interquartile range. PS = persisting symptom, NPS = no persisting symptoms, Q1 = questionnaire 1, Q2 = questionnaire 2.

Extended Data Fig. 6 Sensitivity analysis of PASC symptom group differences.

a , Age matching of symptom groups upon exclusion of individuals <30 years of age. P-value derived from two-sided t -test. b , Results from re-analysis of clinical parameters using a two-sided Wilcoxon test applied to the age-matched PS and NPS groups shown in a . Black asterisks represent significance at p-value.p<0.1, *p<0.05, **p<0.005. c , Test of symptom group effect using a linear model applied to log 2 transformed parameters with correction for acute disease severity group (group B-E). P-value thresholds as in b . d , Re-analysis of clinical parameters by two-sided Wilxocon test in age and acute disease severity matched PS and NPS groups. Age and severity matching is shown in e , p-value thresholds as in b . f , Patient-level findings for iron and inflammatory parameters shown in d . Timepoints of interest are indicated with red arrows. Patients are colored by acute disease severity. Boxplots show minimum, 25 th percentile, median, 75 th percentile and maximum, and outliers beyond 1.5 times the interquartile range. PS = persisting symptom, NPS = no persisting symptoms.

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Hanson, A.L., Mulè, M.P., Ruffieux, H. et al. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19. Nat Immunol 25 , 471–482 (2024). https://doi.org/10.1038/s41590-024-01754-8

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Received : 03 March 2023

Accepted : 12 January 2024

Published : 01 March 2024

Issue Date : March 2024

DOI : https://doi.org/10.1038/s41590-024-01754-8

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