On the Safety of the COVID-19 Convalescent Plasma Treatment: Thrombotic and Thromboembolic Concerns

Round 1

Reviewer 1 Report

In this short opinion article, the authors raised an important question on the overall safety of the convalescent plasma (CP) treatment of COVID-19 patients, where blood plasma from people who've recovered from an illness is used to help others to recover. CP transfusion is used to treat various infectious diseases and the U.S. Food and Drug Administration (FDA) has given emergency authorization for convalescent plasma therapy with high antibody levels to treat COVID-19. However, the authors rightly pointed out that CP transfusion can cause the thrombotic and thromboembolic events that may act as risk factors for adverse complications and death. Therefore, these potential outcomes should be taken into account, especially when conducting population studies on the CP safety.

Author Response

In this short opinion article, the authors raised an important question on the overall safety of the convalescent plasma (CP) treatment of COVID-19 patients, where blood plasma from people who've recovered from an illness is used to help others to recover. CP transfusion is used to treat various infectious diseases and the U.S. Food and Drug Administration (FDA) has given emergency authorization for convalescent plasma therapy with high antibody levels to treat COVID-19. However, the authors rightly pointed out that CP transfusion can cause the thrombotic and thromboembolic events that may act as risk factors for adverse complications and death. Therefore, these potential outcomes should be taken into account, especially when conducting population studies on the CP safety.

RESPONSE: We are thankful to this reviewer for positive comments and appreciation of our work.

Reviewer 2 Report

Dear authors

I have read with interest your opinion I found very important and scientifically sounded. 

Nonetheless, I think the opinion needs: 

• A detailed theoretical approach (further explanation of the usefulness of CP in COVID-19, the explanations of molecular mechanisms associated with adverse effects, ...);
• A table summarizing the previous studies with key findings will be of great help to the readers;
• A graphical abstract could be added.
• I think also that a short paragraph about the limitations of CP in COVID-19 should be added.

Author Response

Reviewer #2

Dear authors

I have read with interest your opinion I found very important and scientifically sounded.

RESPONSE: We are thankful to this reviewer for positive comments, appreciation of our work, constructive critiques, and useful suggestions.

Nonetheless, I think the opinion needs:

A detailed theoretical approach (further explanation of the usefulness of CP in COVID-19, the explanations of molecular mechanisms associated with adverse effects, ...);

RESPONSE: Thank you for pointing this out. Some references discussing the most recent studies where explanation of the advantages/disadvantageous of CP in COVID-19 were added. However, we believe that discussion of the molecular mechanisms associated with the adverse effects of the CP treatment is outside the scopes of this opinion article.

A table summarizing the previous studies with key findings will be of great help to the readers;

RESPONSE: Thank you for pointing this out. However, we do not think that such table is needed. This is because this opinion article is focused on a published study. On the other hand, several previous studies included a similar table(s) and also contain tables representing clinical trials related to the use of CP treatment.

A graphical abstract could be added.

RESPONSE: Thank you for pointing this out. Graphical abstract is added now.

I think also that a short paragraph about the limitations of CP in COVID-19 should be added.

RESPONSE: Thank you for pointing this out. Such a paragraph is added.

Reviewer 3 Report

This opinion manuscript discusses the safety of convalescence plasma (CP) treatment for COVID-19 infected patients.  Special emphasis is given to thrombotic and thromboembolic risks after CP treatment. This topic is very interesting for the readers and relevant for the advancement of COVID-19 therapies. 

I have the following specific suggestions for the authors.

1) Line 24-24. "Recently Kunze et al. [1] reported that near sourced COVID-19 convalescent plasma (CP) is more efficient than distantly sourced CP." The authors should discuss more such findings: why near-sourced CP is more efficient?

 2) The authors should discuss the results of clinical trials regarding the safety of CP treatment for COVID-19.  

3) Please include the following literature: 

COVID-19 Convalescent Plasma Is More than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors. 2021 Aug 11;13(8):1594. 

4) The title should capture the importance of thrombotic and thromboembolic risks for the CP treatment against COVID-19.

Author Response

This opinion manuscript discusses the safety of convalescence plasma (CP) treatment for COVID-19 infected patients.  Special emphasis is given to thrombotic and thromboembolic risks after CP treatment. This topic is very interesting for the readers and relevant for the advancement of COVID-19 therapies.

RESPONSE: We are thankful to this reviewer for positive comments, appreciation of our work, constructive critiques, and useful suggestions.

I have the following specific suggestions for the authors.

1) Line 24-24. "Recently Kunze et al. [1] reported that near sourced COVID-19 convalescent plasma (CP) is more efficient than distantly sourced CP." The authors should discuss more such findings: why near-sourced CP is more efficient?

RESPONSE: Thank you for pointing this out. A brief discussion of this subject is added to the revised manuscript. We also would like to emphasize that the authors of that study provided reliable explanation and reasonable discussion of this phenomenon. However, in our opinion article, we considered aspects which were not explored in Kunze et al study.

2) The authors should discuss the results of clinical trials regarding the safety of CP treatment for COVID-19.

RESPONSE: Thank you for pointing this out. Please note that inclusion of the discussion of the results of clinical trials regarding the safety of CP treatment for COVID-19 does not fit the scopes of this opinion article, which reflects our opinion on the published study by Kunze et al. Furthermore, there are several focused studies that not only include the results of corresponding clinical trials but also analyze them in light of the CP safety, efficacy, and potential side effects.

3) Please include the following literature:

COVID-19 Convalescent Plasma Is More than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors. 2021 Aug 11;13(8):1594.

RESPONSE: Thank you for pointing this out. Indeed, this is a very interesting and important review, and we added it to the revised manuscript.

4) The title should capture the importance of thrombotic and thromboembolic risks for the CP treatment against COVID-19.

Reply: Thank you for pointing this out. The title was changed to reflect the importance of thrombotic and thromboembolic risks.

Round 2

Reviewer 3 Report

The authors have responded constructively to the reviewer's comments.