Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia

Shambel Araya; Mintesnot Aragaw Mamo; Yakob Gebregziabher Tsegay; Asegdew Atlaw; Aschalew Aytenew; Abebe Hordofa; Abebe Edao Negeso; Moges Wordofa; Tirhas Niguse; Mahlet Cheru; Zemenu Tamir

doi:10.1371/journal.pone.0252939

Peer Review History

Original SubmissionNovember 15, 2020
18 Dec 2020 Decision Letter - Elizabeth S. Mayne, Editor PONE-D-20-35898 Blood coagulation parameter abnormalities among patients with confirmed COVID-19 in Ethiopia PLOS ONE Dear Dr. Araya, 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. This is an important and timely paper to consider the abnormalities of haematological parameters in an African context and in COVID-19 disease. There are, however, unfortunately significant numbers of typographical errors and word omissions which make the sense of the paper difficult to follow in some cases. For example, the authors refer to a "prolonged" but do not indicate which parameter. There are, in addition, a number of references which need to be included (especially in the discussion). Please submit your revised manuscript by Jan 31 2021 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'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Elizabeth S. Mayne, M.D. Academic Editor PLOS ONE Additional Editor Comments: This is an important and timely paper to consider the abnormalities of haematological parameters in an African context and in COVID-19 disease. There are, however, unfortunately significant numbers of typographical errors and word omissions which make the sense of the paper difficult to follow in some cases. For example, the authors refer to a "prolonged" but do not indicate which parameter. There are, in addition, a number of references which need to be included (especially in the discussion). Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap in the Discussion, Abstract, and other sections, between your submission and the following previously published works: - https://applications.emro.who.int/emhj/v26/09/1020-3397-2020-2609-999-1004-eng.pdf - https://www.hematology.org/COVID-19/COVID-19-and-coagulopathy - https://pubmed.ncbi.nlm.nih.gov/32702124/ We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications. Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work. We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough. 3. Please state whether you validated the questionnaire prior to testing on study participants. Please provide details regarding the validation group within the methods section. 4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ 6. Please amend the manuscript submission data (via Edit Submission) to include author MogesWordofa. 7. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 1 in your text; if accepted, production will need this reference to link the reader to the Table. [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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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 ****** 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: No Reviewer #2: 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: This study is a simple evaluation of coagulation parameters that occur durning covid. The authors detected an increase in the prothrombin time and a decrease in the platelet count which correlated with the severity of infection. It is interesting and is worthy of publication Reviewer #2: The study is relevant in the African context and will assist in the management of COVID patients in this often under resourced environment. The article however requires review of the English grammar. ****** 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 Reviewer #2: 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. Attachments Attachment Submitted filename: PONE-D-20-35898_reviewer SL.pdf https://doi.org/10.1371/journal.pone.0252939.r001
Revision 1
11 Jan 2021 Author Response Cover letter Shambel Araya Addis Ababa University Addis Ababa, Ethiopia Email: shambelaraya8@gmail.com Date: January 1, 2021 To: PLOS ONE Journal Dear Editorial: We are glad to write this response that our paper entitled “Blood coagulation parameter abnormalities among patients with confirmed COVID-19 in Ethiopia” (Submission ID: PONE-D-20-35898) has been requested to review for publication in PLOS ONE journal. We are pleased to have an opportunity to make our paper revised and we have greatly appreciated the reviewers’ and editor’s comments and suggestions were very helpful overall. In revising the paper, we have carefully considered reviewers’ and editor’s comments and suggestions on our revised submission. As instructed, we have attempted to succinctly explain changes made in reaction to all comments and reply to each comment in point-by-point fashion as follows: Response to Editor’s comments Additional Editor comments Comment. “This is an important and timely paper to consider the abnormalities of haematological parameters in an African context and in COVID-19 disease. There are, however, unfortunately significant numbers of typographical errors and word omissions which make the sense of the paper difficult to follow in some cases. For example, the authors refer to a "prolonged" but do not indicate which parameter. There are, in addition, a number of references which need to be included (especially in the discussion).” Response: As suggested by the editor we thoroughly went through the manuscript and revised the typographical, grammatical, editorial, and word omissions. Journal requirements When submitting your revision, we need you to address these additional requirements. Comment #1. “Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.” Response #1: we strictly followed PLOS ONE's style requirements during preparation and revision of our manuscript as suggested by the editor. Comment #2. “Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap in the Discussion, Abstract, and other sections, between your submission and the following previously published works: - https://applications.emro.who.int/emhj/v26/09/1020-3397-2020-2609-999-1004-eng.pdf - https://www.hematology.org/COVID-19/COVID-19-and-coagulopathy - https://pubmed.ncbi.nlm.nih.gov/32702124/ We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications. Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work.” Response #2. As per the suggestion of the editor, we have revised different sections of manuscript to reduce text overlap with the mentioned previous studies and cite the utilized sources as follows: • Abstract, Background section: ‘Infection with corona virus disease 2019 (COVID-19) could be complicated with coagulopathy and high risk of thromboembolic events.’ Revised as “Coagulopathy and thromboembolic events are among the complications of Corona Virus disease 2019 (COVID-19).” • Abstract, conclusion section: ‘We found an abnormal pattern of coagulation parameters and association of advanced age and co-morbidities with a high rate of mortality in severe COVID-19 patients, which should be taken into consideration in their hospital management. Revised as “In this study, prolonged prothrombin time and high INR were found among severe and critical COVID-19 patients. Thrombocytopenia and prolonged APTT were dominant in COVID-19 patients older than 55 years. Thus, we recommend emphasis to be given for monitoring of platelet count, PT, APTT and INR in hospitalized COVID-19 patients management.” • Discussion part first paragraph: ‘COVID-19, which is caused by SARS-CoV-2, has spread across the globe. Although most patients recover within 1 to 3 weeks, COVID-19 has already caused >1.2 million deaths worldwide and more than 1400 in Ethiopia as of October 30,2020 according to WHO report (15). Dysregulation of coagulation produces a coagulopathy associated with hyper coagulability as evidenced by venous and arterial thrombosis and multi-organ dysfunction. Up to 20% of affected patients require hospitalization, and the mortality rate in such patients is high (16, 17). Coagulopathy is one of the most significant prognostic factors in patients with COVID-19 and is associated with increased mortality and admission to critical care (14, 18). Most commonly observed coagulopathy in patients hospitalized with COVID-19 (COVID-19-associated coagulopathy) is characterized by increased coagulation parameters like PT, APTT and INR levels (19, 20).’ Revised as “The COVID-19 pandemic has brought major impact on health care globally. It has already caused >1.2 million deaths worldwide and more than 1400 in Ethiopia as of October 30,2020 according to WHO report(15). Coagulation abnormalities are indicated as frequent findings in COVID-19 patients and associated with poor prognosis and survival(7). Similarly, it is also indicated that coagulopathy which is resulted due to dysregulation of coagulation and associated with hypercoagulability as evidenced by venous and arterial thrombosis and multiorgan dysfunction(16); is one of the most significant prognostic factors in patients with COVID-19 and associated with increased hospitalization, admission to critical care, and mortality(14, 17-19). Previous studies indicated that coagulopathy in patients hospitalized with COVID-19 is characterized by increase in coagulation parameters such as PT, APTT and INR levels(20, 21).” • Discussion part 3rd Paragraph: “As for all coagulopathies, treatment of the underlying condition is paramount. Experience to date suggests that COVID-19 infection infrequently leads to bleeding despite abnormal coagulation parameters (23,24). Supportive care including blood product transfusion should be individualized (24, 25). Blood component therapy should not be instituted on the basis of laboratory results alone, but reserved for those who are bleeding requires an invasive procedure, or who are otherwise at high risk for bleeding complications (25).” Revised as “Treatment of the underlying condition is suggested to be paramount in coagulopathies. It is shown that bleeding is not common clinical manifestation in COVID-19 infections despite abnormal coagulation parameters (23,24). Along these, it is suggested that supportive care including blood product transfusion should be individualized in COVID -19 patients (25, 26). Laboratory findings alone should not be taken as basis for instituting blood transfusion therapy, rather it should be reserved for those who are bleeding, require an invasive procedure, or who are otherwise at high risk for bleeding complications(26, 27)” Discussion part 4th Paragraph: “Considerable evidence indicates that COVID-19 is associated with a hyper-coagulable state. Thus, despite anticoagulant thrombo-prophylaxis, different studies have reported that rates of venous thromboembolism (VTE) and arterial thrombosis ranging from 15% to 30% in critically ill patients with COVID-19 and ∼7% in those admitted to medical wards (26-28). Clotting of access catheters, dialysis membranes, and extracorporeal circuits has also been reported. Furthermore, in patients dying from COVID-19, autopsy studies reveal unsuspected deep vein thrombosis and multiple thrombi in the vessels of the lungs, kidneys, and other organs (9, 27). These findings have prompted some clinicians to use treatment doses of heparin or low- molecular-weight heparin instead of prophylactic doses in critically ill COVID-19 patients (12,25, 29). Revised as “Evidences indicate that COVID-19 is associated with a hyper-coagulable state. Venous thromboembolism (VTE) and arterial thrombosis ranging from 15% to 30% were found in critically ill patients with COVID-19 and about 7% in those admitted to medical wards (28-30). Clotting is reported from different medical devices used, deep vein thrombosis and multiple thrombi in the vessels of the lungs, kidneys and other organs from autopsy of patients died of Covid-19 (9, 29). These indicate clinicians to use therapeutic doses of heparin or low-molecular-weight heparin instead of prophylactic doses in critically ill COVID-19 patients (12, 26, 31). • Conclusion part: “We recommend monitoring platelet count, PT, APTT and INR. Worsening of these parameters indicates progressive severity of COVID-19 infection and predicts that more aggressive critical care will be needed; experimental therapies for COVID-19 infection might be considered in this setting. Improvement of coagulation parameters along with improving clinical condition provides confidence that stepping down of aggressive treatment may be appropriate.” Revised as “In this study, prolonged prothrombin time and high INR were found among severe and critical COVID-19 patients. Thrombocytopenia and prolonged APTT were dominant in COVID-19 patients older than 55 years. Thus, we recommend emphasis to be given for monitoring of platelet count, PT, APTT and INR in hospitalized COVID-19 patients management. Comment #3. “Please state whether you validated the questionnaire prior to testing on study participants. Please provide details regarding the validation group within the methods section.” Response #3. Not applicable. We did not used questionnaire in this study. Comment #4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Response #4. All the available data were included in the manuscript. Comment #5. ” PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ” Response #5. “Already linked” Comment #6. “Please amend the manuscript submission data (via Edit Submission) to include author Moges Wordofa.” Response #6. Comment accepted and author included Comment #7. “We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 1 in your text; if accepted, production will need this reference to link the reader to the Table.” Response #7. Comment accepted and corrected accordingly. Response to comments and suggestions inserted in the PDF format Manuscript Comment # 1: in the abstract section. A prolonged (insert analytical parameter that was prolonged) was present in 48.8% of study subjects with COVID-19? Response 1: Parameter inserted and and revised as “A prolonged prothrombin time was found among 46.8% of study subjects with COVID-19” Comment # 2: In the abstract section. The comment to remove the interpretation and conclusion. Response #2. Comment accepted and modified accordingly. Comment #3. On Title. “Blood coagulation parameter abnormalities among in hospitalized patients with confirmed COVID-19 in Ethiopia” Response #3: Accepted and modified as: “Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia” Comment#4: in the abstract, method part: ‘…were estimated by auto analyzer.” ‘Which parameter?’. Response to #5. Although the comment was to indicate which parameter, since the parameter are already mentioned we perceived it as to mean which auto analyzer and inserted the specific analyzer used as_”…..HUMACLOT DUE PLUS coagulation analyzer (Wiesbaden, Germany)” Comment #6. In the introduction part. “ ….WHO. Write out abbreviation in full the first time it is used”. Response #6. Corrected as suggested. …..World Health Organization(WHO). Comment #7. In the laboratory analysis part, “…HUMACLOT DUE PLUS.. Insert trademark symbol e.g. R or TM.” Response #7. Accepted and modified as “…HUMACLOT DUE PLUS coagulation analyzer (Wiesbaden, Germany) Comment #8. In the laboratory analysis part, “…Beckman coulter DxH 600 automated hematology analyzer.. Insert trademark symbol e.g. R or TM.” Response #8. Accepted and modified as “…Beckman coulter DxH 600 automated hematology analyzer Comment #9. “Thrombocytopenia and abnormal coagulation parameters (PT, APTT and INR) could be considered as important indicators of COVID-19 disease severity. This statement belongs in the discussion section of the article.” Response # 9: Accepted and removed as suggested. Comment #10. In discussion part. ‘Thrombocytopenia, defined as platelet count less than 100×10⁹ cells per L were independently associated with severity. Insert reference.’ Response #10: Comment accepted; reference inserted as suggested. “Thrombocytopenia, defined as platelet count less than 100×10⁹cells/L were independently associated with COVID-19 severity(34)” Comment 11. Discussion Part. “As many studies reported that the coagulopathy associated with COVID-19 is characterized by thrombocytopenia, prolongation of the prothrombin time, high levels of D-dimer, and elevated levels of fibrinogen, factor VIII, and von Willebrand factor. Insert reference” Response #11. Comment accepted; reference inserted as suggested. “Many studies reported that coagulopathy associated with COVID-19 is characterized by thrombocytopenia, prolongation of the prothrombin time, high levels of D-dimer, and elevated levels of fibrinogen, factor VIII, and von Willebrand factor(3, 11, 16).” Comment #12. Conclusion part. “We recommend monitoring platelet count, PT, APTT and INR. ...in patients hospitalized COVID-19 patients. Response #12. Comment accepted and modified as “We recommend monitoring platelet count, PT, APTT and INR in hospitalized COVID-19 patients.” Looking forward to hearing from you. Thank you again for your consideration! Sincerely, Shambel Araya (BSc, MSc) Corresponding author https://doi.org/10.1371/journal.pone.0252939.r002
31 Mar 2021 Decision Letter - Elizabeth S. Mayne, Editor PONE-D-20-35898R1 Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia PLOS ONE Dear Dr. Araya, 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. ============================== Although both reviewers were happy that their concerns were addressed, there are some minor predominantly typographical and grammatical errors. Please review attached reviews. ============================== Please submit your revised manuscript by May 15 2021 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'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Elizabeth S. Mayne, M.D. 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. [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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ****** 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 ****** 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 ****** 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 study adds to local knowledge of the clinical manifestations and outcomes in patients with COVID and has the potential to assist with clinical decisions. Various final changes have been recommended as indicated on the uploaded edited article. ****** 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 [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. Attachments Attachment Submitted filename: PONE-D-20-35898_R1_reviewer SL 23_01_2021.pdf https://doi.org/10.1371/journal.pone.0252939.r003
Revision 2
2 Apr 2021 Author Response Cover letter Shambel Araya Addis Ababa University Addis Ababa, Ethiopia Email: shambelaraya8@gmail.com Date: April, 2021 To: PLOS ONE Journal Dear Editorial: We are glad to write this response that our research article entitled “Blood coagulation parameter abnormalities among patients with confirmed COVID-19 in Ethiopia” (Submission ID: PONE-D-20-35898R1) has been requested to review for publication in PLOS ONE journal. We are pleased to have an opportunity to make our paper revised and we have greatly appreciated the reviewers’ and editor’s comments and suggestions were very helpful overall. In revising the paper, we have carefully considered reviewers’ and editor’s comments and suggestions on our revised submission. As instructed, we have attempted to succinctly explain changes made in reaction to all comments and reply to each comment in point-by-point fashion as follows: Response to comments and suggestions inserted in the PDF format of the Manuscript � Comment 1: Abstract, methods section: “...Estimated by...” was replaced by “...determined on...” as per your suggestion in line 34 � Comment 2: Abstract, Result section: “among” is replaced with ‘in’ in line 36 � Comment 3: Abstract, Result section: “…Prolonged prothrombin time and high INR were seen among 53.3% severe and 51% critical 38 patients with COVID-19 manifestation…. Thrombocytopenia was detected in 22.1% of COVID-19 39 patients” has replaced with… and a prolonged prothrombin time and elevated INR with 53.3% of study subjects with severe and 51 % of critically COVID patients…” in line 37-39 � Comment 4: abstract, conclusion section. In this study, prolonged prothrombin time and high INR were found among severe and critical COVID-19 patients. Revised: In this study, prolonged prothrombin time and high INR were detected in 50% of severe and critical COVID-19 patients � Comment: abstract, conclusion section. Delete management Response: Accepted and deleted in line 45 � Comment 6: Introduction section. Replace showed with demonstrated that Response: Accepted and replaced � Comment 7: …Introduction section. coagulation parameters could be an efficient measure for improving the clinical management and predicting the prognosis of patients with SARS COV-2(7)… Revised: …coagulation parameters could be an efficient measure for predicting the prognosis of patients with SARS COV-2(7) and guiding management… � Comment 8: Introduction section: Accepted and modified as follow “Different studies also support that COVID-19 patients are at high risk of developing disseminated intravascular coagulation (12, 13). It is also indicated that comparison of reports from various populations related to the clinical course, outcome of COVID-19 and blood coagulation profile in these patients are necessary to help the management and treatment of the disease (12, 14). Moreover, this routine coagulation parameter tests could be used as potential indicators for COVID-19 in individuals having typical clinical manifestations that would be inputs for prompt patient management especially in resource limited settings where the high-tech gold standard RT-PCR is not widely available, like Ethiopia” Revised: Several studies have also demonstrated the increased occurrence of intravascular disseminated coagulopathy (DIC) in patients with COVID-19 (12, 13). The result of blood coagulation parameters in COVID-19 can also guide management decisions and improve outcomes (12, 14). Moreover, routine coagulation parameter tests results could potentially be utilized in symptomatic patients in resource limited settings with inadequate access to COVID-19 RT-PCR, as in Ethiopia, to raise suspension of this infection. However, data on coagulation profiles among Ethiopian COVID-19 patients is not readily available, like Ethiopia. Comment8: Introduction section Replace “…find out…” with “...Determine…” Response: accepted and replaced as per your suggestion � Comment 9: Delete “and” in line 88 � Line 92: Replace “…of…” with “…for…” � Line 94: Replace “…Was taking…” with “…were receiving…” � Line 95: Change “According to” in to “…with…” Response: Accepted and modified accordingly Comment 10: Methods, laboratory section. Eight milliliters of venous blood were collected by professional nurses working in the treatment center: five milliliters in EDTA for platelet count, three milliliters in 3.2% sodium citrated Revised: Venous bloods were collected by professional nurses working in the treatment center: 5 mL in EDTA and 3 mL in 3.2% sodium citrated � Comment 11: Insert trade mark for each instruments and software’s Response: accepted and inserted as follow in line 99-102 � Comment12: remove Addis Ababa, Ethiopia, 2020 from table 1 Response: Deleted as per your suggestion � Comment 13: Result section line 120-122 “Severe and critical groups showed differences in sex ratio and age distribution. In severe and critical groups, majority were males and elderly (Table 2).” Revised: Severe and critical groups showed differences in sex ratio and age distribution. In severe (36.6%) and critical groups (48.5%), were elderly males of the age of >55 years old. y (Table 2). � Comment 14: result section table 3: remove “…admitted to Millennium COVID-19 treatment center Addis Ababa, Ethiopia…” Response: accepted and removed table heading � Comment 15: Result section line 127-129, rewrite “Prolonged PT value was found among males (49.8%) than females (41%) and it has a significant association with gender (P = 0.045).” Revised: accepted and modified as “Prolonged PT values were demonstrated more frequently among males (49.8%) than females (41%) and this difference was significantly different (P = 0.045).” Comment 16: replace study subjects with individuals Response accepted and replaced in line 130 � Comment 16 result section line 135-136: rearrange “…patients aged older than 55 years had thrombocytopenia. Thrombocytopenia was higher among…” in to Revised: modified as “…patients aged older than 55 years had thrombocytopenia and the occurrence was higher among…” � Comment 17: insert “…Result of …” in table 3 heading Response: accepted and modified as follow “Result of coagulation parameters in patients with severe COVID-19 according to different variables” Comment 18: Discussion section: Replace “…had brought…” with “...had a…” Delete indicated as Remove findings � Comment 19: Rearrange the paragraph as below for “Coagulation abnormalities are indicated as frequent findings in COVID-19 patients and associated with poor prognosis and survival(7). Similarly, it is also indicated that coagulopathy which is resulted due to dysregulation of coagulation and associated with hypercoagulability as evidenced by venous and arterial thrombosis and multiorgan dysfunction (16); is one of the most significant prognostic factors in patients with COVID-19 and is associated with increased hospitalization, admission to critical care, and mortality” Response: accepted Revised: Coagulation abnormalities are frequent in COVID-19 patients and are associated with poor prognosis and reduced survival(7). Dysregulation of coagulation and associated with hypercoagulability in patients with COVID manifest as venous and arterial thrombosis and multiorgan dysfunction (16); which are poor prognostic markers resulting in increased mortality and hospitalization and ICU admission � Comment 20: discussion section Line 151: remove “…levels...” Line 153 insert “…more frequent…” Line 153: remove “…than moderate ones…” Line 159: replace “… alongside these, it is suggested that…” with “and” Line 164: replace “…Evidence…” with “…published studies…” Response: Accepted and modified as per your suggestion Line 167: replace “…clotting is reported from…” with “…Abnormal thrombosis of…” Line 167-170: rewrite it as follow for “…Clotting is reported from different medical devices used, deep vein thrombosis and multiple thrombi in the vessels of the lungs, kidneys and other organs from autopsy of patients died of Covid-19 (9, 29). These indicate clinicians to use…” Response: Accepted and rephrase as follow Revised: “…Abnormal thrombosis of different medical devices, deep vein thrombosis and multiple thrombi in the vessels of the lungs, kidneys and other organs at autopsy of patients who died of Covid-19 have been reported serving as the impetus behind guidelines (9, 29)which support the use…” Line 173-175: rewrite it as follow for “Studies across suggested that routine coagulation tests can be considered as a significant marker to help clinicians assess prognosis and severity of patients with COVID-19…” Response: Accepted and rephrase as follow Revised: (34). “...Studies suggest that routine coagulation test results are markers of disease severity and assist in management decision…” Line 184: Insert “… in critically ill non-COVID patients…” Response: accepted Line 186-189: rephrase the sentence “COVID-19-associated coagulopathy is however unique with a much-decreased platelet count (9, 36-38)” Revised: Published studies support that COVID-19-associated coagulopathy is characterized by a decreased platelet count (9, 36-38). Dear all, we are very grateful for your valuable comments and for your time Looking forward to hearing from you. Thank you again for your consideration! Sincerely, Shambel Araya (BSc, MSc, PhD fellow) https://doi.org/10.1371/journal.pone.0252939.r004
26 Apr 2021 Decision Letter - Elizabeth S. Mayne, Editor PONE-D-20-35898R2 Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia PLOS ONE Dear Dr. Araya, 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. ============================== The reviewer felt that the manuscript was substantially improved but there are still a number of grammatical and typographical errors that should be corrected. Again, it is recommended that the manuscript is reviewed by a native English language speaker. ============================== Please submit your revised manuscript by Jun 10 2021 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'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Elizabeth S. Mayne, M.D. 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. [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: (No Response) ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ****** 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 ****** 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 ****** 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 article provides information pertaining to the coagulation abnormalities in the local African context that could potentially assist with the treatment of patients with COVID and improve outcomes. ****** 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 [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. Attachments Attachment Submitted filename: PONE-D-20-35898_R2 Blood coagulation markers Ethiopia COVID.pdf https://doi.org/10.1371/journal.pone.0252939.r005
Revision 3
5 May 2021 Author Response General Comments The reviewer felt that the manuscript was substantially improved but there are still a number of grammatical and typographical errors that should be corrected. Again, it is recommended that the manuscript is reviewed by a native English language speaker. Dear reviewers and editors � We have carefully consider your comments and we have incorporated all your comments and recommendations � The manuscript have also reviewed by a native English language speaker Specific comments � Comment 1: Abstract, background section: � “Thus”, “taken as” and “COVID-19” was removed as per your suggestion in line 28 & 29 � Comment 2: Abstract, method section: � Insert trade mark: inserted � Remove tests and replace it with statistical analysis results: accepted and replaced � Comment 3: Result section: “with” is replaced with ‘in’ in line � Comment 4: abstract, conclusion section. � Replace “around” with “more than” � Comment5: Introduction section: Dear editor and reviewers, all comments and suggestions given in introduction section were accepted and amended accordingly � Remove “heavily” in line 52 � Replace 49,578, 490 with “more than 1.4 million” in line 53 � Insert with lung injury in line 56 � Remove and critical cases with � Comment 6: method section: Dear editor and reviewers, all comments and suggestions given in method section were accepted and amended accordingly � Insert “personal identifying” in line 87: accepted and inserted � Delete “time”, “its” in line 107 and 108 � Replace Platelet with platelets in line 108 � Comment 6: Result section: Dear editor and reviewers, all comments and suggestions given in result section were accepted and amended accordingly � Delete Y in line 126 � Delete N=455 in table 1 � Replace “higher” with “elevated” � Move heading of table 3 to the top � Comment 6: Discussion section: Dear editor and reviewers, all comments and suggestions given in discussion section were accepted and amended accordingly � Replace “and” with “is” in line 153 � Replace in “patients with COVID” with “and” in line 151 � Delete “resulting in increased mortality and hospitalization and ICU admission” in line 153 � Change manifest in to manifests and increase in to increases � Delete “(9.5%-47%)” in line 160 � Insert “More frequently” in line 176 and 177 � Rephrase the sentences from line 188-193 Before: The degree of coagulation abnormalities in critically ill non-COVID patients correlates with disease severity and predict the risk of thrombosis, the need for ventilator support, and mortality. Published studies support that COVID-19-associated coagulopathy is characterized by a decreased platelet count (9, 36-38). Patients with critical COVID-19 infection and a cytokine storm have an extreme hyper-coagulable state. Modified: Published studies indicate that COVID-19-associated coagulopathy is characterized by a decreased platelet count (9, 36-38)and a cytokine storm with an extreme hyper-coagulable state. � Comment 6: Discussion section: � Replace “APTT” with “clotting time assays” Response: Dear editors and reviewers all of the above listed comments, recommendations and suggestions are accepted, replaced and corrected and we thank you very much for your valuable comments & time. Looking forward to hearing from you. Thank you again for your consideration! Sincerely, Shambel Araya (BSc, MSc, PhD fellow) https://doi.org/10.1371/journal.pone.0252939.r006
26 May 2021 Decision Letter - Elizabeth S. Mayne, Editor Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia PONE-D-20-35898R3 Dear Dr. Araya, 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. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. 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. Kind regards, Elizabeth S. Mayne, M.D. Academic Editor PLOS ONE Additional Editor Comments (optional): 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ****** 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 ****** 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 ****** 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 information contained in the article will add to much needed local African data pertaining to COVID-19 and assist in appropriate care of patients in order to improve clinical outcomes. ****** 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 Attachments Attachment Submitted filename: PONE-D-20-35898_R3_reviewer SL.pdf https://doi.org/10.1371/journal.pone.0252939.r007
Formally Accepted
28 May 2021 Acceptance Letter - Elizabeth S. Mayne, Editor PONE-D-20-35898R3 Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia Dear Dr. Araya: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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 Dr. Elizabeth S. Mayne Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0252939.r008

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .