Thromboembolism and Bleeding in COVID-19

Round 1

Reviewer 1 Report

I have read with interest the review manuscript by Durak K. on the interplay between COVID-19 and coagulation dysfunctions resulting either in thromboses (both venous and arterial) or hemorrhages.

The manuscript is well written and easy to follow, especially in the "Mechanisms" part.

What I find lacking are the clinical parts that would greatly benefit from an extension of the studies considered. In particular, more recent metaanalysis should be added (e.g. Boonyawat et al. Thromb J 2020; Gretz et al. Front Med 2021; Nannoni et al. Int J Stroke 2020) together with the total number of studies/patients reviewed in the "prevalence" section.

Moreover, the section of "Thromboprophylaxis" should report types and dosages of the recommended anticoagulants used according to guidelines.

Author Response

1) I have read with interest the review manuscript by Durak K. on the interplay between COVID-19 and coagulation dysfunctions resulting either in thromboses (both venous and arterial) or hemorrhages. The manuscript is well written and easy to follow, especially in the "Mechanisms" part.

A1) Dear Reviewer A, thank you for the response and I appreciate your comments.

2) What I find lacking are the clinical parts that would greatly benefit from an extension of the studies considered. In particular, more recent metaanalysis should be added (e.g. Boonyawat et al. Thromb J 2020; Gretz et al. Front Med 2021; Nannoni et al. Int J Stroke 2020) together with the total number of studies/patients reviewed in the "prevalence" section.

A2) Indeed, these and other meta-analysis are of great benefit for this review. Therefore, I added the above mentioned studies to provide the prevalence section with more accurate numbers. I also added important studies to fourth section on "screening" and highlighted the fact that evidence for routine or clinically guided screening is scarce. Additionally, I made a new literature search and added multiple recent RCTs to the sixth section on "Thromboprophylaxis".

3) Moreover, the section of "Thromboprophylaxis" should report types and dosages of the recommended anticoagulants used according to guidelines.

A3) It is true that the thromboprophylaxis section missed accurate information on types and dosages. I rewrote the whole paragraph and also added information on RCTs that were published a few weeks ago. Now I clearly described types and dosages from high quality evidence for different indications. Furthermore, I added literature on ongoing RCTs which will provide evidence for current issues about this topic in the following months or years. 

Reviewer 2 Report

This is a good review article concerning thromboembolism and bleeding in patients affected with Covid-19 infection.

The paper is well-written and comprehensive and I do not find space for major or minor remarks.

 

Author Response

1) This is a good review article concerning thromboembolism and bleeding in patients affected with Covid-19 infection. The paper is well-written and comprehensive and I do not find space for major or minor remarks.

A1) Dear Reviewer 2, thank you for the effort in reviewing our manuscript. I appreciate your positive response. During the review process, I also added more literature (recent RCTs and systematic analysis) to the clinical parts and formulated a conclusion. 

Reviewer 3 Report

The manuscript by Koray Durak is a narrative review of the increased risk for thromboembolic and bleeding complications in patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.  Overall, I find this a well-timed article, summarized in a pleasant to read manuscript, scientifically accurate, complete and fully comprehensive to the reader.  The reference section is appropriate to back up the points made in the article. However, there are a couple of issues that need to be taken into consideration.

The first resides in a relative lack of novelty, as recent reviews on the same topic were recently published, some of which have been even cited by the Author (PMID: 33217420).  To be honest, we must recognize that these were focused on specific clinical settings while the article under review attempts to describe COVID-19 related TE and bleeding of patients who are hospitalized, admitted to ICU, or receiving extracorporeal life support.  In addition, the Author might want to consider discussing the recent papers by Dalager-Pedersen M, et al. published in Clin Infect Dis (PMID: 33400771) and by Li W, et al. published in Aging (Albany NY) (PMID: 33818421).

The second is related to the general structure of the manuscript, which appears truncated as there is no concluding paragraph that reports an interpretation of the existing data in the literature or the author's opinion regarding the management and treatment of thrombosis in patients with COVID-19.

Author Response

1) The manuscript by Koray Durak is a narrative review of the increased risk for thromboembolic and bleeding complications in patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.  Overall, I find this a well-timed article, summarized in a pleasant to read manuscript, scientifically accurate, complete and fully comprehensive to the reader.  The reference section is appropriate to back up the points made in the article. However, there are a couple of issues that need to be taken into consideration.

A1) Dear Reviewer 3, thank you for your valuable comments and effort in reviewing the manuscript. I appreciate your generally positive comments. 

2) The first resides in a relative lack of novelty, as recent reviews on the same topic were recently published, some of which have been even cited by the Author (PMID: 33217420).  To be honest, we must recognize that these were focused on specific clinical settings while the article under review attempts to describe COVID-19 related TE and bleeding of patients who are hospitalized, admitted to ICU, or receiving extracorporeal life support.  In addition, the Author might want to consider discussing the recent papers by Dalager-Pedersen M, et al. published in Clin Infect Dis (PMID: 33400771) and by Li W, et al. published in Aging (Albany NY) (PMID: 33818421).

A2) Indeed, more recent papers were necessary to improve the novelty and overall quality of the manuscript. I added the above mentioned papers and results of recently published RCTs. Therefore, the second paragraph "Prevalences" is provided with more accurate numbers (line 31-61). I added existing literature for screening of thromboembolism in COVID-19 patients (line 196-214). Thereby, I highlighted the fact that a direct comparison of patients with and without routine screening is not existing, and further research is necessary (line 196-214). Then, I rewrote the whole "Thromboprophylaxis" paragraph (line 227-304) because I added the results of very recent RCTs that provide high quality evidence for important clinical decisions (such as the use of therapeutic doses of anticoagulation only in noncritically ill patients). I also mentioned some ongoing RCTs which are necessary to answer current questions in this field (such as the effectiveness and safety of extended prophylaxis). 

3) The second is related to the general structure of the manuscript, which appears truncated as there is no concluding paragraph that reports an interpretation of the existing data in the literature or the author's opinion regarding the management and treatment of thrombosis in patients with COVID-19.

A3) Yes, the conclusion paragraph was missing. I added interpretation of the existing evidence and my own summarizing opinion in a conclusion (line 313-325). I also mentioned the ongoing trials we are waiting for in the future and the need for more research in the field of screening for VTE.