Minimal change disease following COVID-19 vaccination: A systematic review

Konstantinos S. Kechagias; Joshua D. Laleye; Jan Drmota; Georgios Geropoulos; Georgios Kyrtsonis; Marina Zafeiri; Konstantinos Katsikas Triantafyllidis; Dimitra Stathi

doi:10.1371/journal.pone.0297568

Peer Review History

Original SubmissionMay 12, 2023
3 Sep 2023 Decision Letter - Rajendra Bhimma, Editor PONE-D-23-13443Minimal change disease following COVID-19 vaccination a systematic reviewPLOS ONE Dear Dr.Konstantinos S. Kechagias, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Oct 15 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. 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Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Additional Editor Comments: Thank you for your submisson of the manuscript "Minimal change disease following COVID-19 vaccination a systematic review". Three reviewers have raised concerns and these need to be addressed. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: No Reviewer #2: Yes Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: I Don't Know Reviewer #3: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ******** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Please see the updated articles on various adverse effect of astrazeneca and other mrna covid vaccine.Authors missed the major complication such as sinus venous thrombosis as well as inflammatory cns disorders post vaccination and other relevant findings. Also the information can be obrained from Medicines and Healthcare products Regulatory Agency (MHRA) data as well from Vaccine adverse events reporting system Reviewer #2: The research question is clear. The inclusion and exclusion criteria are well defined. The search strategy, study selection and data extraction appear comprehensive. Data synthesis is appropriate. The interpretation of the findings and conclusion are accurate. The following revisions are required: Line 29 change “renal dysfunction” to more appropriate term – Glomerular disease or chronic kidney disease Line 45 change terms – “into remission “ Line 49 change “clinical doctors” to clinicians in the paper Line 91 correct spelling of vaccine Line 147/8 biopsy reported in only 71% of cases ( ? diagnosis) – important limitation , if these were relapses then a second biopsy would be unlikely , although first time diagnosis would require a biopsy , specify if primary or relapse. First line of discussion “renal dysfunction” term should be changed Second line of paragraph : Results in context of literature: “Evidence points towards T cell dysfunction being a major Mechanism” Is this immune dysregulation with dysfunction of T regulatory cells as with other cases of MCD? Line 3-4 “glomerular capillary wall” could be restated as the glomerular filtration barrier. Last line “requires histologic confirmation in adults” is fundamental to diagnosis. MCD is a histological diagnosis. Unless there was relapse which did not warrant a biopsy, then all other cases would require confirmatory histology. If this is not so, then it should be listed as a limitation of the review. Reviewer #3: It is a relevant topic with billions of doses of vaccines used in such a short period of time and also Being RNA based. 1. Need clarity on that only 76% had histological classification of their nephrosis. what criteria were used to establish minimal change. 2. Was there any particular vaccine type that caused the most or least number of nephrotic syndrome cases. I know that then we have to look at the number of vaccine doses but was there a particular type involved with the new cases compared to the relapses? 3. There are 2 diabetics with a possibility of diabetic neohropathy? Was minimal change confirmed on histology? 4. The other secondary involvement were cardiac problems such as hypertension, hyperlipidaemia, and arrthytmias althoiugh hypertension and hyperlipdaemis can be caused by the nephrosis 5. If only 76% had renal histology, which criteria were used to prove minimal change? 6. Infections that were mentioned in the discussion such as Hep 'B' cause membranous nephropathy. It is well written. Just the above queries or clarification. ******* 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: Yes: shitiz sriwastava Reviewer #2: No Reviewer #3: 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. 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Revision 1
30 Oct 2023 Author Response Dear Editor, Thank you for considering our article ‘Minimal change disease following COVID-19 vaccination: a systematic review’ for publication in your journal. We enclose below a point-by-point response to the reviewers’ comments and a revised version of the manuscript. We have also adjusted the format according to the journal’s guidance. We look forward to your reply. Yours sincerely Konstantinos Kechagias MD, MSc Clinical research fellow Institute of Reproductive and Developmental Biology, Department of Metabolism Digestion and Reproduction, Imperial College London Reviewer #1: Please see the updated articles on various adverse effect of astrazeneca and other mrna covid vaccine. Authors missed the major complication such as sinus venous thrombosis as well as inflammatory cns disorders post vaccination and other relevant findings. Also the information can be obtained from Medicines and Healthcare products Regulatory Agency (MHRA) data as well from Vaccine adverse events reporting system. Thank you for the comment. Although different types of adverse events secondary to Covid-19 vaccine have been recognized, the focus of the current literature review was minimal change disease. In the introduction section of the article, we briefly mention the plethora of other adverse events related to Covid-19 vaccines and we have now also included the MHRA guidance as reference. Line 72. Reviewer #2: The research question is clear. The inclusion and exclusion criteria are well defined. The search strategy, study selection and data extraction appear comprehensive. Data synthesis is appropriate. The interpretation of the findings and conclusion are accurate. The following revisions are required: Line 29 change “renal dysfunction” to more appropriate term – Glomerular disease or chronic kidney disease. Line 45 change terms – “into remission “ Line 49 change “clinical doctors” to clinicians in the paper Line 91 correct spelling of vaccine. We thank the reviewer for the annotations. The above have now been changed as per recommendations. Regarding line 91, the term vaccin was used in order to identify articles including words such as vaccine, vaccines and vaccination. Lines 29, 45 and 49. Line 147/8 biopsy reported in only 71% of cases (? diagnosis) – important limitation, if these were relapses then a second biopsy would be unlikely, although first time diagnosis would require a biopsy, specify if primary or relapse. We thank the reviewer for the comment. We elaborated on the use of biopsy as a diagnostic tool. Biopsy reports were provided for 67 cases (71.2%, 67/94) and were consistent with MCD. MCD was confirmed with biopsy in 76 cases (80.8%, 76/94). Sixteen cases (17%, 16/94) were a relapse and biopsy was not repeated. In two cases (2.1%), diagnosis was based on clinical suspicion (Nagai et al, Nakazawa et al). Lines 147 and 148. First line of discussion “renal dysfunction” term should be changed. Thank you for the annotation. Renal dysfunction has been replaced by kidney disease. Line 161 Second line of paragraph: Results in context of literature: “Evidence points towards T cell dysfunction being a major Mechanism” Is this immune dysregulation with dysfunction of T regulatory cells as with other cases of MCD? We thank the reviewer for this comment. Yes, this refers to the dysfunction of T regulatory cells and the hypothesis that a glomerular permeability factor is produced that subsequently attacks the glomerular membrane, which has been proposed in the past as a potential mechanism for MCD. This has now been clarified in the manuscript. Line 175 Line 3-4 “glomerular capillary wall” could be restated as the glomerular filtration barrier. Thank you for the annotation. This has now been restated as suggested. Lines 3 and 4. Last line “requires histologic confirmation in adults” is fundamental to diagnosis. MCD is a histological diagnosis. Unless there was relapse which did not warrant a biopsy, then all other cases would require confirmatory histology. If this is not so, then it should be listed as a limitation of the review. We thank the reviewer for the comment, and we agree. Biopsy reports were provided for 67 cases (71.2%, 67/94) and were consistent with MCD. MCD was confirmed with biopsy in 76 cases (80.8%, 76/94). Sixteen cases (17%, 16/94) were relapses and biopsy was not repeated. In two cases (2.1%), diagnosis was based on clinical suspicion. Lines 147-149 Reviewer #3: It is a relevant topic with billions of doses of vaccines used in such a short period of time and also Being RNA based. 1. Need clarity on that only 76% had histological classification of their nephrosis. what criteria were used to establish minimal change. We thank the reviewer for the comment and we agree. Biopsy reports were provided for 67 cases (71.2%, 67/94) and were consistent with MCD. MCD was confirmed with biopsy in 76 cases (80.8%, 76/94). Sixteen cases (17%, 16/94) were a relapse and biopsy was not repeated. In two cases (2.1%), diagnosis was based on clinical suspicion (Nagai, Nakazawa). Lines 147-149 2. Was there any particular vaccine type that caused the most or least number of nephrotic syndrome cases. I know that then we have to look at the number of vaccine doses but was there a particular type involved with the new cases compared to the relapses? We thank the reviewer for the comment. In the results section, both the vaccine type and the number of doses before the development of nephrotic syndrome are mentioned. The majority of the patients received COMIRNATY (58.5%, 55/94), followed by COVID-19 Vaccine Moderna (20.2%, 19/94) and VAXZEVRIA (14%, 13/94), while 4 participants received COVID-19 Vaccine Janssen (3.2%, 3/94) and CoronaVac (1%, 1/94). In one case vaccine type was reported as modRNA (1%, 1/94). The majority of patients developed symptoms after the first dose (55.5%, 52/94), followed by the second dose (39.3%, 37/94), third dose (2.2%, 2/94), booster (1%, 1/94), both first and second doses (1%, 1/94), while in one case relevant data was not provided (1%, 1/94). Lines 138-143 3. There are 2 diabetics with a possibility of diabetic nephropathy? Was minimal change confirmed on histology? The other secondary involvement were cardiac problems such as hypertension, hyperlipidaemia, and arrthytmias although hypertension and hyperlipdaemis can be caused by the nephrosis Thank you for your comment. Patients with the above comorbidities had histological diagnosis of MCD. 5. If only 76% had renal histology, which criteria were used to prove minimal change? We thank the reviewer for this comment. Biopsy reports were provided for 67 cases (71.2%, 67/94) and were consistent with MCD. MCD was confirmed with biopsy in 76 cases (80.8%, 76/94). Sixteen cases (17%, 16/94) were relapses and biopsy was not repeated. In two cases (2.1%), diagnosis was based on clinical suspicion. Lines 147-149 6. Infections that were mentioned in the discussion such as Hep 'B' cause membranous nephropathy. We thank the reviewer for this comment. We mentioned Hep B and other viruses as triggering factors for primary glomerulonephrosis including MCD given that a similar pathophysiological mechanism could be implicated. Attachments Attachment Submitted filename: response to reviewers.docx https://doi.org/10.1371/journal.pone.0297568.r002
9 Jan 2024 Decision Letter - Rajendra Bhimma, Editor Minimal change disease following COVID-19 vaccination a systematic review PONE-D-23-13443R1 Dear Dr. Kostantionos S Kechagias We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. 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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: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: I Don't Know Reviewer #3: I Don't Know ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes Reviewer #3: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: The authors have indicated that they will amend the paper according to each point raised. If this is done completely then they have complied with the review. Reviewer #3: It is a relevant review ion that the complication of nephrotic syndrome or relapse is an infrequent occurrernce of Covid vaccination.The practising physicians need to know of the renal complications of Covid vaccination. Also alert the researchers to do a prospective studies as regards incidence, severity, associated factors, type of vaccine etc. This was a systemic review of the literature, where their is no uniformity of the reported information and almost a third were case reports. In my opinion it is a relevant review to spark prospective studies. ****** 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 ******** https://doi.org/10.1371/journal.pone.0297568.r003
Formally Accepted
24 Feb 2024 Acceptance Letter - Rajendra Bhimma, Editor PONE-D-23-13443R1 PLOS ONE Dear Dr. Kechagias, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Rajendra Bhimma Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0297568.r004

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