How does COVID-19 vaccination affect long-COVID symptoms?

Ali A Asadi-Pooya; Meshkat Nemati; Mina Shahisavandi; Hamid Nemati; Afrooz Karimi; Anahita Jafari; Sara Nasiri; Seyyed Saeed Mohammadi; Zahra Rahimian; Hossein Bayat; Ali Akbari; Amir Emami; Owrang Eilami

doi:10.1371/journal.pone.0296680

. 2024 Feb 7;19(2):e0296680. doi: 10.1371/journal.pone.0296680

How does COVID-19 vaccination affect long-COVID symptoms?

Ali A Asadi-Pooya ^1,^2,^*, Meshkat Nemati ¹, Mina Shahisavandi ¹, Hamid Nemati ¹, Afrooz Karimi ¹, Anahita Jafari ¹, Sara Nasiri ¹, Seyyed Saeed Mohammadi ^1,³, Zahra Rahimian ¹, Hossein Bayat ¹, Ali Akbari ⁴, Amir Emami ⁵, Owrang Eilami ⁶

Editor: Peivand Bastani⁷

PMCID: PMC10849259 PMID: 38324547

Abstract

Objective

The current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition.

Methods

This was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate.

Results

In total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) who received at least one dose of any vaccine had long long- COVID symptoms (p = 0.032).

Conclusions

In people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. However, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.

1. Introduction

The WHO (World Health Organization) declared a COVID-19 pandemic on March 2020. COVID-19 is a global problem and many people got infected during this pandemic. Furthermore, in some patients, this disease was not limited to the acute phase [1–3]. COVID-19 may cause post-acute phase lingering symptoms; this is called long-COVID syndrome or post-COVID-19 condition [4]. Long-COVID syndrome is characterized by chronic symptoms of fatigue, cough, exercise intolerance, cognitive dysfunction, etc. This condition has been reported by many adults who survived COVID-19 [5–8].

In a previous study of 4,681 adult participants, we observed that 62% of the survivors of severe COVID-19 (requiring hospitalization) reported suffering from long-COVID symptoms [8].

The underpinning pathomechanisms of long-COVID are not entirely clear yet; however, immunological responses to the infection may play significant roles in causing post-acute phase lingering symptoms of COVID-19. Post-COVID immunological dysfunction may persist for months [9, 10]. Therefore, it is plausible to hypothesize that COVID vaccination may affect the symptoms of post-COVID condition by manipulating the immune system.

Vaccination against COVID-19 can reduce the death rate and hospitalization rate related to COVID-19 [11]. However, how vaccinations can impact long-term symptoms of post-COVID condition need to be investigated [12]. A few studies suggested that there is a relationship between receiving a vaccination and getting long COVID-19 syndrome [3, 13].

In the current study, we aimed to identify the longevity of symptoms associated with long-COVID in adults who had reported suffering from this condition (in our previous study [8]) in association with their COVID vaccination status.

2. Methods

2.1. Participants

This was a follow-up study of 4,681 adult patients with COVID-19 who had documented positive tests on real-time polymerase chain reaction for COVID-19 from our previous study [8]. We randomly selected every other participant in our database of patients from our previous study (sorted by their phone numbers in the database). If someone did not answer our phone call, we selected the previous patient in the list who was initially skipped.

2.2. Data collection

For all the participants, the current data (S1 Appendix that was adopted from phase 1 of the study) were collected during a phone call interview in January-February 2022 (11 months after the initial study and more than 14 months after their hospital admission due to COVID-19). After obtaining oral consent over the phone to share their information for research purposes, we inquired about their current health status and if they agreed to participate in the study (consented orally). We asked whether the patient has noticed any particular problems during the past seven days, compared with their pre-COVID-19 condition. We specifically asked about experiencing these problems during the past seven days in order to minimize the risk of recall bias. We defined long long-COVID (long-COVID lasting more than one year after the initial infection and hospitalization) as patients who had reported long COVID-19-associated symptoms and complaints in phase 1 of the study and who also had the same symptoms and complaints in the current follow-up phase of the study.

We asked whether the patients experienced another episode of COVID-19 (after phase 1 of the study; self-declared); we excluded patients with a COVID-19 reinfection. Finally, we asked whether the patients received any COVID-19 vaccines (and the number of doses they received). It is noteworthy to mention that the COVID-19 mass vaccination program in Iran started after phase 1 of this study, so none of the people could have received any vaccine before their enrollment in this study (at phase 1).

2.3. Statistical analyses

Kolmogorov-Smirnov normality test was performed. Values were presented as mean ± standard deviation (SD) or median/ interquartile range (IQR) (based on their normality) for continuous variables and as the number (percent) of subjects for categorical variables. We categorized the vaccination status as not vaccinated vs. vaccinated (i.e., 1 or 2, or 3 doses). We investigated whether the persistence of long long-COVID (long-COVID lasting more than one year after the initial infection) had any associations with the vaccination status of the participants. The following statistical tests were applied as appropriate: Chi-square test and t-test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression test. A p-value (2-sided) less than 0.05 was considered significant.

2.4. Standard protocol and ethics approvals

The Shiraz University of Medical Sciences Institutional Review Board approved this study (IR.SUMS.Rec.1399.022 & m/h/19/91/8225). Informed consent was obtained from all the participants.

3. Results

We made 4112 phone calls of which 1419 were not answered, 220 people refused to participate in the study, 90 individuals were deceased, and 395 persons reported experiencing reinfection with COVID-19. In total, 1988 people were included in the current study [1041 male (52.4%) and 947 female (47.6%) participants]. The median age of the participants was 52 years (minimum: 18, maximum: 97, and interquartile range: 23 years). Of the studied participants, 1236 people (62.2%) reported having long-COVID in phase 1 of the study; these were selected for the next steps of the analyses.

In the current phase, 543 (27.3%) individuals reported suffering from long long-COVID (43.9% of those with long-COVID in phase 1). (8) Fifty-one people (4.1%) never received any vaccine and 1185 individuals received at least one dose of a vaccine [24 individuals (1.9%) received one dose, 392 persons (31.7%) received two doses, and 769 participants (62.2%) received three doses of a COVID-19 vaccine]. The follow-up durations of the participants (after their initial infection) based on their vaccination status were not significantly different: not vaccinated (17.1±1.9 months) vs any doses of vaccine (16.8±2.1 months); p = 0.350.

We investigated whether the persistence of long-COVID (long long-COVID) had any associations with the vaccination status of the participants. Chi-square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) with any doses of vaccine had long long-COVID (p = 0.032; univariate analysis); 11 out of 24 (45.8%) of those with one dose, 181 out of 392 (46.2%) of the participants with two doses, and 336 out of 769 (43.7%) of the people with three doses of vaccine had long long-COVID. Table 1 shows long long-COVID symptoms in association with the vaccination status of the participants. When binary logistic regression test was applied (vaccination status and sex as covariates and experiencing long long-COVID as the dependent variable), sex was not associated with experiencing long long-COVID (p = 0.454) while receiving any dose of COVID vaccine was significantly associated with long long-COVID (p = 0.032; OR = 1.96; 95% CI: 1.06–3.63).

Table 1. Long long-COVID symptoms in association with the vaccination status of the participants^*.

Lingering symptoms	Vaccinated people (N = 1185)	Unvaccinated people (N = 51)	P value^**
Muscle weakness	152 (12.8%)	3 (5.9%)	0.142
Muscle pain	95 (8%)	0	-
Joint pain	96 (8.1%)	1 (1.9%)	0.110
Fatigue	238 (20.1%)	5 (9.8%)	0.070
Sleep difficulty	45 (3.8%)	2 (3.9%)	0.963
Shortness of breath	151 (12.7%)	4 (7.8%)	0.300
Chest pain	31 (2.6%)	0	-
Palpitation	33 (2.8%)	0	-
Cough	45 (3.8%)	1 (1.9%)	0.497
Excess sputum	25 (2.1%)	1 (1.9%)	0.942
Loss of smell	17 (1.4%)	1 (1.9%)	0.758
Loss of taste	4 (0.3%)	0	-
Sore throat	6 (0.5%)	0	-
Headache	35 (2.9%)	1 (1.9%)	0.679
Dizziness	22 (1.9%)	0	-
Concentration difficulty	43 (3.6%)	0	-
Excess sweating	15 (1.3%)	1 (1.9%)	0.667
Exercise difficulty	200 (16.9%)	6 (11.8%)	0.337
Walking difficulty	143 (12.1%)	4 (7.8%)	0.361
Diarrhea	5 (0.4%)	0	-
Abdominal pain	7 (0.6%)	0	-
Loss of appetite	5 (0.4%)	0	-
Long Long-COVID	528 (44.6%)	15 (29.4%)	0.032^***

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*Some patients reported multiple symptoms.

** Chi-square test.

*** The chi-square statistic with Yates correction is 3.959. The p-value is 0.046.

4. Discussion

As of 15 February 2022, 73.5% of the population in Iran received at least one dose, 65.3% two doses, and 25.7% received their third (booster) dose of a COVID vaccine field [14]. In the current study of adult participants with severe COVID-19 (requiring hospitalization) and subsequent long-COVID syndrome, we observed that receiving the COVID-19 vaccine had a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection (long long-COVID). Contrary to our finding, a recent report (not an analytical study) noted that some people have found that their post-acute phase COVID-related symptoms decreased or disappeared after receiving at least one dose of a COVID-19 vaccine [15]. An article suggested that COVID-19 vaccination is associated with a lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection (a concept that is different from our objective) [11].

Having said all the above, we should keep in mind that in general, vaccines reduce the risk of long-COVID by lowering the chances of contracting COVID-19, in the first place [16]. In addition, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). In one recent study, infection-acquired immunity boosted with vaccination remained high for more than one year after infection (longer than that with two doses of vaccines) [17]. Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.

Previous studies have suggested that a severe COVID-19 (e.g., requiring hospitalization) may cause a more severe immune response and cytokine storm, and therefore, may cause more long-lasting organ damage (e.g., to the brain, lungs, etc.) [5–8]. Another similar possibility that might explain the symptoms of long-COVID is that the lingering immune response triggered by the initial infection can generate antibodies and other immunological reactions against various organs [9, 10]. Other hypothetical explanations for long-COVID include a persistent viral reservoir and also “viral ghosts”, which are fragments of the virus that linger after the infection has been cleared, but are still capable of stimulating the immune system [18].

On the other hand, different vaccines against SARS-CoV-2 stimulate the human immune system to provide protective immunity against the virus. The evidence from animal studies supports the idea that antibodies targeting the SARS-CoV-2 spike protein, the same protein that many vaccines use to trigger a protective immune response, might cause collateral damage [19, 20]. A recent study suggested that virus-mimicking anti-idiotype antibodies that are present after infection or after vaccination may potentially explain some of the long-COVD symptoms [21]. Therefore, it is plausible to hypothesize that vaccines may prolong the existing symptoms of long COVID by stimulating the immune response. A recent report even suggested that vaccines may rarely cause long-COVID-like symptoms (without a history of infection) [19]. However, a study of the effectiveness of the COVID-19 vaccine in the prevention of post-COVID-19 conditions suggested that COVID-19 vaccination both before and after having COVID-19 significantly decreased post-COVID-19 conditions during the study period although vaccine effectiveness was low [22]. Future studies should specifically investigate the underlying pathophysiology of long-COVID and its relation to various types of COVID vaccines [23]. There are other studies that suggested COVID-19 vaccination may improve long COVID symptoms [24, 25]. However, one research conducted in India, concluded that developing long-COVID was related to receiving the vaccination [26]. In another study, some symptoms of long-COVID include hair loss and ocular symptoms worsened by vaccination [27]. Finally, one study did not find any significant associations between long-COVID symptoms and vaccination [28].

In our internal discussions, we discussed the issue that reporting any potential adverse effects of COVID vaccines may embolden the position of anti-vaccine movements and may harm vaccine-hesitant people. However, we came to the conclusion that the scientific community has the obligation to investigate the potential adverse effects of any and all vaccines and clearly and without any political considerations report them to the public. This strategy would strengthen the position of the scientific community in the eyes of the public, so when the scientific community announces that the benefits of COVID-19 vaccines (prevention of severe illness and death) outweigh the potential risks and adverse effects significantly, the public trust the scientific community. Furthermore, this move enables the scientific community to recognize the pitfalls and adverse effects of the existing vaccines and paves the road for further investigations to improve the development of better vaccines in the future. Understanding adverse effects that are potentially associated with vaccines could help those currently suffering and, if a link is established, it could not only help guide the design of the next generation of vaccines but also perhaps identify those at high risk for serious adverse effects [19]. After all, “we should not be averse to adverse events” [19].

5. Limitations

The data on long long-COVID were not collected prospectively. In addition, we did not investigate asymptomatic reinfections in this study. Furthermore, we did not undertake any objective measures to study the symptoms, and we did not have a control group. Finally, we could not ask about the types of vaccines that the patients received due to the specifications in our ethical approval from the Shiraz University of Medical Sciences Institutional Review Board. As of 15 February 2022, 11 COVID vaccines have received approval for use in Iran [29].

6. Conclusion

In people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID-19 vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. Having said that, vaccines generally reduce the risk of long-COVID by lowering the chances of contracting COVID-19, in the first place. Furthermore, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a past history of COVID-19, receive vaccines to protect themselves against this fatal viral infection. Future studies should specifically investigate the underlying pathophysiology of long-COVID and its relation to various types of COVID vaccines.

Supporting information

S1 Checklist. STROBE statement-checklist of items that should be included in reports of cross-sectional studies.

(DOCX)

Click here for additional data file.^{(28.4KB, docx)}

S1 Appendix. Long long-COVID and vaccine study, Fars, Iran.

(DOCX)

Click here for additional data file.^{(14.8KB, docx)}

S1 File. Inclusivity in global research.

(DOCX)

Click here for additional data file.^{(64.4KB, docx)}

Data Availability

Data sharing is only possible with permission from Shiraz University of Medical Sciences. Data are owned by the vice chancellor for Medical Affairs at Shiraz University of Medical sciences and the Institutional Review Board has imposed restrictions at data sharing. Please contact info@sums.ac.ir for data sharing inquires.

Funding Statement

The author(s) received no specific funding for this work.

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PLoS One. doi: 10.1371/journal.pone.0296680.r001

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PONE-D-23-01917How does COVID-19 vaccination affect long-COVID symptoms?PLOS ONE

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The literature review is partial and incomplete, and some recent and relevant contributions should be cited and discussed: i.e., 10.1017/S0950268822001418.

The theoretical framework should be discussed more in detail.

The choice of methodology needs to be clearly stated and motivated.

The estimated model must be justified in light of the literature on this specific topic.

Data should be defined more clearly. A link to the data source must be reported.

Descriptive statistics are absent.

Diagnostic tests are absent.

Robustness checks are absent.

The results should be discussed more in detail.

Comparisons with previous studies are absent.

Conclusions are too short.

Policy implications are weak.

Further research should be indicated.

Limitations of the study are not provided.

Proofreading by a native speaker is required.

The editing does not follow the journal’s guidelines.

Some typos must be fixed.

How does the paper enrich the knowledge of the scientific community?

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. No

Confidential to Editor

1. Do you have any potential or perceived competing interests that may influence your review? Please review our Competing Interests policy and declare any potential interests that you feel the Editor should be aware of when considering your review. If you have no competing interests, please write "I have no competing interests." I have no competing interests.

2. Did you receive any assistance in preparing this review (e.g. from a post-doc or graduate student)? If yes, please include their name below. No

3. If accepted, do you think this submission should be highlighted on the PLOS ONE website? PLOS ONE does not evaluate manuscripts based on perceived significance or readership. We aim to provide tools for readers to filter and evaluate our publications. (optional) No

Do you want to get recognition for this review on a Web of Science researcher profile?

If you opt in, your Web of Science profile will automatically be updated to show a verified record of this review in full compliance with the journal’s review policy. If you don’t have a Web of Science profile, you will be prompted to create a free account.

Yes

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: No

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: No

**********

5. Review Comments to the Author

Reviewer #1: The Abstract must report the aim of the study, the basic information on the sample (time span, countries analyzed), the empirical methodology used, the main findings, and the relevant policy implications.

Introduction and Literature Review should be split into two different sections.

The literature review is partial and incomplete, and some recent and relevant contributions should be cited and discussed: i.e., 10.1017/S0950268822001418.

The theoretical framework should be discussed more in detail.

The choice of methodology needs to be clearly stated and motivated.

The estimated model must be justified in light of the literature on this specific topic.

Data should be defined more clearly. A link to the data source must be reported.

Descriptive statistics are absent.

Diagnostic tests are absent.

Robustness checks are absent.

The results should be discussed more in detail.

Comparisons with previous studies are absent.

Conclusions are too short.

Policy implications are weak.

Further research should be indicated.

Limitations of the study are not provided.

Proofreading by a native speaker is required.

The editing does not follow the journal’s guidelines.

Some typos must be fixed.

How does the paper enrich the knowledge of the scientific community?

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2024 Feb 7;19(2):e0296680. doi: 10.1371/journal.pone.0296680.r002

Author response to Decision Letter 0

18 Jul 2023

Dear Editor in Chief,

We are so thankful to the reviewers and editorial team for their insightful comments that helped us to improve the current version.

Associated Editor Comments

1-Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Thanks for pointing it out. We checked our manuscript and prepared it to meet the journal's guidelines.

2. We noticed you have some minor occurrences of overlapping text with the following previous publication(s), which needs to be addressed:

- https://www.science.org/content/article/rare-cases-coronavirus-vaccines-may-cause-long-Covid-symptoms

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. A further consideration is dependent on these concerns being addressed.

The mentioned website considered seventeen citations of our manuscript. We have reviewed our manuscript again.

3. In the ethics statement in the Methods, you specified that verbal consent was obtained. Please provide additional details regarding how this consent was documented and witnessed, and state whether this was approved by the IRB.

Our manuscript was approved by the Ethical Committee of Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.Rec.1399.022 & m/h/19/91/8225). As the data was obtained by phone, we asked our patients for consent. If they agreed, we continued to interview.

4. Please include a complete copy of PLOS’ questionnaire on inclusivity in global research in your revised manuscript. Our policy for research in this area aims to improve transparency in the reporting of research performed outside of the researchers’ own country or community. The policy applies to researchers who have traveled to a different country to conduct research, research with Indigenous populations or their lands, and research on cultural artifacts. The questionnaire can also be requested at the journal’s discretion for any other submissions, even if these conditions are not met. Please find more information on the policy and a link to download a blank copy of the questionnaire here: https://journals.plos.org/plosone/s/best-practices-in-research-reporting. Please upload a completed version of your questionnaire as Supporting Information when you resubmit your manuscript.

Thanks for suggesting this issue, we are uploading a completed version of the questionnaire.

OK.

Supporting information files are added at the end of our manuscript.

Reviewers comment

1- The Abstract must report the aim of the study, the basic information on the sample (time span, countries analyzed), the empirical methodology used, the main findings, and the relevant policy implications.

Thank you for your comment. The aim of the study has been written in simple words in order to clarify the concept better.

2-Introduction and Literature Review should be split into two different sections. The Introduction should highlight the relevance of the topic, the novelty of the results, the importance of policy implications, the sample’s choice, the methodology’s appropriateness, the data used, the contribution to the literature, and the limitations of the study.

As suggested by the reviewer. In the revised manuscript, both sections are covered in the introduction part.

3-The literature review is partial and incomplete, and some recent and relevant contributions should be cited and discussed: i.e., 10.1017/S0950268822001418.

New recent and relevant contributions are added to our article.

4-The theoretical framework should be discussed more in detail.

Revised.

5-The choice of methodology needs to be clearly stated and motivated.

Revised.

6-The estimated model must be justified in light of the literature on this specific topic.

There was no model.

7-Data should be defined more clearly. A link to the data source must be reported.

see the data availability statement.

8-Descriptive statistics are absent.

As it is mentioned, In total, 1988 people were included in the current study [1041 male (52.4%) and 947 female (47.6%) participants]. The median age of the participants was 52 years (minimum: 18, maximum: 97, and interquartile range: 23 years). Of the studied participants, 1236 people (62.2%) reported having long COVID in phase 1 of the study; these were selected for the next steps of the analyses.

9-Diagnostic tests are absent.

Thank you for your comment, we have added the PCR test as a diagnostic test in the method part.

10-Robustness checks are absent.

Not clear.

11-The results should be discussed more in detail.

Revised.

12-Comparisons with previous studies are absent.

We added some more comparisons to clarify our concept better. Some recent studies are added in the discussion and introduction parts.

13-Conclusions are too short.

We have changed the conclusion and discussed that in more detail.

14-Policy implications are weak.

Revised.

15-Further research should be indicated.

revised.

16-Limitations of the study are not provided.

Limitations of our study were added.

17-Proofreading by a native speaker is required.

All spelling and grammatical errors have been corrected.

18-The editing does not follow the journal’s guidelines.

We have checked our manuscript and revised our manuscript to follow the journal’s guidelines.

19-Some typos must be fixed.

We have fixed the typos.

20-How does the paper enrich the knowledge of the scientific community?

See the conclusion.

Attachment

Submitted filename: response letter.docx

Click here for additional data file.^{(19.3KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0296680.r003

Decision Letter 1

Wondwossen Amogne Degu

20 Sep 2023

PONE-D-23-01917R1How does COVID-19 vaccination affect long-COVID symptoms?PLOS ONE

Dear Dr. Asadi-Pooya,

Please submit your revised manuscript by Nov 04 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Wondwossen Amogne Degu, M.D

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

Reviewer #3: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

6. Review Comments to the Author

Reviewer #2: The manuscript has been revised and is now acceptable for publication. Congratulations to the contributing authors.

Reviewer #3: 1. Results section was well described but it would be clearer if the authors show the results espeically specific symptoms (listed in the appendix 1) in the table to let the audience sees the differences of long-covid symptoms among participants groups. e.g. vaccinated vs unvaccinated, reinfection.

2. Logistic regression could also be applied to study the factors that could contibute to the long-long COVID symptoms although no control in the study but at least between persistent and non-persistent long-long COVID

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

**********

PLoS One. 2024 Feb 7;19(2):e0296680. doi: 10.1371/journal.pone.0296680.r004

Author response to Decision Letter 1

21 Sep 2023

Dear Editor in Chief,

We are so thankful to the reviewers for their insightful comments that helped us to improve the current version.

Reviewer #3:

1. Results section was well described but it would be clearer if the authors show the results especially specific symptoms (listed in the appendix 1) in the table to let the audience sees the differences of long-covid symptoms among participants groups. e.g. vaccinated vs unvaccinated, reinfection.

Response. A table is included as suggested.

2. Logistic regression could also be applied to study the factors that could contribute to the long-long COVID symptoms although no control in the study but at least between persistent and non-persistent long-long COVID.

Response. While this is a valuable comment, it is not related to the question of our work (the longevity of symptoms associated with long COVID in adults in association with their COVID vaccination status). Besides, the groups were very imbalanced (51 vs 1185) for detailed statistical analyses with other tests.

Attachment

Submitted filename: response letter 2.docx

Click here for additional data file.^{(14.8KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0296680.r005

Decision Letter 2

Peivand Bastani

12 Dec 2023

PONE-D-23-01917R2How does COVID-19 vaccination affect long-COVID symptoms?PLOS ONE

Dear Dr. Asadi-Pooya,

==============================

Dear Authors,

Thanks for submitting the new version of your manuscript, based on my opinion and the reviewer`s comment, the following comment has not been addressed yet and needs more work.:

- Logistic regression could also be applied to study the factors that could contribute to the long-long COVID symptoms although no control in the study but at least between persistent and non-persistent long-long COVID

==============================

Please submit your revised manuscript by Jan 26 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Peivand Bastani

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear Authors,

Thanks for submitting the new version of your manuscript, based on my opinion and the reviewer`s comment, the following comment has not been addressed yet and needs more work.:

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Reviewer #2: The paper has been extensively revised and is now acceptable for publication. As such, I would like to extend my congratulations to the authors.

Reviewer #3: Thank you to the authors for the response. I only have one last suggestion.

In the table. It is better to have percentage of each symptoms behind the number to let reader understand the information easily.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

**********

PLoS One. 2024 Feb 7;19(2):e0296680. doi: 10.1371/journal.pone.0296680.r006

Author response to Decision Letter 2

14 Dec 2023

Dear Editor in Chief,

We are thankful to the reviewers for their insightful comments that helped us to improve the current version.

Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression test.

When binary logistic regression test was applied (vaccination status and sex as covariates and experiencing long long-COVID as the dependent variable), sex was not associated with experiencing long long-COVID (p = 0.454) while receiving any dose of COVID vaccine was significantly associated with long long-COVID (p = 0.032; OR = 1.96; 95% CI: 1.06-3.63).

Table 1 is revised with percentages included.

Attachment

Submitted filename: response letter 3.docx

Click here for additional data file.^{(14.5KB, docx)}