Virus-Negative Necrotizing Coronary Vasculitis with Aneurysm Formation in Human SARS-CoV-2 Infection

Round 1

Reviewer 1 Report

Sir, 

I have recently reviewed the manuscript "Virus-negative Necrotizing Coronary Vasculitis with Aneurysm Formation in Human Sars-Cov-2 Infection" submitted by Andrea Frustaci and co-workers as a Brief Report to Infectious Disease Reports (ISSN 2036-7449). 

The authors report a case of myopericarditis associated with SARS-CoV-2 infection with necrotizing vasculitis of intramural vessels. In brief, this is an interesting and well-documented case. However, there are some outstanding issues. 

Authors mentioned in the abstract that they have detected, and I quote: "necrotizing coronary vasculitis of intramural vessels". However, later - see line 52- they also concluded that "Coronary arteries were normal". As far as I can understand the message of this case report,  the authors observed a small-vessel vasculitis (of intramural arterioles). This must be properly distinguished because there is a morphological distinction between coronary arteries (right or left) and their subsequent small branches (including intramural arterioles).  For the proper approach to nomenclature, the authors can use guide and reference here: https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-6/Cardiac-involvement-in-small-and-medium-sized-vasculitides-Title-Cardiac-invo

Also, I believe that authors should briefly discuss their interesting case and highlight principal differences of the presented case from Kawasaki/Kawasaki-like disease (seen predominantly in children).  I believe this might be a very substantial (educative) outcome for readers. 

I appreciate that the authors try to present the case in a broader context of molecular pathophysiological background (line 78, e.g. modulators of IL-1B, IL-6). Relevant publications should reference this, e.g., Brabek et al. Int J Mol Sci. 2020 Oct 26;21(21):7937. doi: 10.3390/ijms21217937  and also van de Veerdonk FL Care. 2020 Jul 18;24(1):445. doi: 10.1186/s13054-020-03166-0.

The follow-up is brief; I believe that authors should reveal whether the markers of inflammation (e.g. CRP and troponin) were normal. 

Minor point: I believe that lines 117-137 should be filled by authors or omited if necessary; this seems to be a general MDPI instruction. 

To conclude, the authors present interesting data, and they could easily perfect their manuscript. I believe they can finish this task in virtually no time, and I am keen to see it for a final review and approval as soon as possible.

Author Response

Sir, 

I have recently reviewed the manuscript "Virus-negative Necrotizing Coronary Vasculitis with Aneurysm Formation in Human Sars-Cov-2 Infection" submitted by Andrea Frustaci and co-workers as a Brief Report to Infectious Disease Reports (ISSN 2036-7449). 

The authors report a case of myopericarditis associated with SARS-CoV-2 infection with necrotizing vasculitis of intramural vessels. In brief, this is an interesting and well-documented case. However, there are some outstanding issues. 

Authors mentioned in the abstract that they have detected, and I quote: "necrotizing coronary vasculitis of intramural vessels". However, later - see line 52- they also concluded that "Coronary arteries were normal". As far as I can understand the message of this case report,  the authors observed a small-vessel vasculitis (of intramural arterioles). This must be properly distinguished because there is a morphological distinction between coronary arteries (right or left) and their subsequent small branches (including intramural arterioles).  For the proper approach to nomenclature, the authors can use guide and reference here: https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-6/Cardiac-involvement-in-small-and-medium-sized-vasculitides-Title-Cardiac-invo

Reply: We thanks the reviewer for his/her comments. The definition in line 52 has been modified in “Epicardial coronary arteries” .

Also, I believe that authors should briefly discuss their interesting case and highlight principal differences of the presented case from Kawasaki/Kawasaki-like disease (seen predominantly in children).  I believe this might be a very substantial (educative) outcome for readers. 

Reply: The difference between our case and Kawasaki disease has been discussed (pag 2 line 72)

I appreciate that the authors try to present the case in a broader context of molecular pathophysiological background (line 78, e.g. modulators of IL-1B, IL-6). Relevant publications should reference this, e.g., Brabek et al. Int J Mol Sci. 2020 Oct 26;21(21):7937. doi: 10.3390/ijms21217937  and also van de Veerdonk FL Care. 2020 Jul 18;24(1):445. doi: 10.1186/s13054-020-03166-0.

Reply: The suggested references have been added to the text (ref 2-3)

The follow-up is brief; I believe that authors should reveal whether the markers of inflammation (e.g. CRP and troponin) were normal. 

Reply: The normalization of CPR and troponin was added to the text in line 65.

Minor point: I believe that lines 117-137 should be filled by authors or omited if necessary; this seems to be a general MDPI instruction. 

Reply: We apologize for the mistake that has been corrected.

To conclude, the authors present interesting data, and they could easily perfect their manuscript. I believe they can finish this task in virtually no time, and I am keen to see it for a final review and approval as soon as possible.

Reviewer 2 Report

Interesting subject.

 

I found from my personal experience , two missing points:

 

among cardiotropic viruses you did not look for H1N1;

serum levels of c3 and c4 should be added in the text 

 

Author Response

REVIEWER 2

Interesting subject.

I found from my personal experience , two missing points:

among cardiotropic viruses you did not look for H1N1 

serum levels of c3 and c4 should be added in the text 

Reply: The influenza A virus H1N1 was included in the screening (line 61). Serum levels of C3 and C4 were within normal limits (line 30)

Reviewer 3 Report

This brief report discusses a case of myopericarditis associated with SARS-CoV-2 infection with necrotizing coronary vasculitis of intramural vessels, giving rise to biventricular apical microaneurysms and to electrical instability.

The abstract section should be revised, after the modifications suggested below.

The introduction section does not introduce the thematic sufficiently (for example, no references were used to introduce the thematic). Nevertheless, I suggest improving the aims of the study that should be clearly written.

In the "Methods and Results" section the authors missed several important information. For example, Which is the clinical history of the patient? Is he healthy? Has he suffered from other comorbidities? These are important information that should be inserted. Moreover, it could be useful to insert the main blood tests performed at admission and at discharge.

In the discussion section, the authors missed comparing their data with international data. Please, improve this section.

Other issues

The authors did not insert information about the "Institutional Review Board Statement" and "Informed Consent Statement".

Author Response

This brief report discusses a case of myopericarditis associated with SARS-CoV-2 infection with necrotizing coronary vasculitis of intramural vessels, giving rise to biventricular apical microaneurysms and to electrical instability.

The abstract section should be revised, after the modifications suggested below.

The introduction section does not introduce the thematic sufficiently (for example, no references were used to introduce the thematic). Nevertheless, I suggest improving the aims of the study that should be clearly written.

Reply: We thank the reviewer fior his/her comments. The reference 1 has been added to the manucript and the aims have been better clarified.

In the "Methods and Results" section the authors missed several important information. For example, Which is the clinical history of the patient? Is he healthy? Has he suffered from other comorbidities? These are important information that should be inserted. Moreover, it could be useful to insert the main blood tests performed at admission and at discharge.

Reply: According with the reviewer suggestions the Introduction and the Method and result section was implemented.

In the discussion section, the authors missed comparing their data with international data. Please, improve this section.

Reply:The section has been implemended

Other issues

The authors did not insert information about the "Institutional Review Board Statement" and "Informed Consent Statement".

Reply: We apologize for the mistake that has been corrected.

 

 

Round 2

Reviewer 3 Report

The authors have improved the manuscript. Please, check-> Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of out Institution. ->INSERT CODE

Author Response

Reviewer: The authors have improved the manuscript. Please, check-> Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of out Institution. ->INSERT CODE

Reply:We thanks the reviewer for his/her comments. The Ethics Committee approval code is EudraCT 2016-003014-28