SARS-CoV-2-Associated Obliterative Arteritis Causing Massive Testicular Infarction

Round 1

Reviewer 1 Report

For the first time,iIn the present case report, the authors describe a massive testicular ischemic infarction in the context of COVID-19 infection, while orchitis and impaired spermatogenesis have  been previously associated with COVID-19 infection

The main message in the present case recalls the attention of general practitioners and urologists when  facing testicular pain in the context of SARS-CoV-2 infection representing a useful diagnostic suggestion.

The manuscript requires minor spell check  before to be  published.

Author Response

The authors thank the reviewer's comments. Minor English changes have been performed, as requested.

Reviewer 2 Report

clinpract-1170328

SARS-CoV-2-associated obliterative arteritis causing massive testicular infarction

Dámaso Parrón , Ane Gartzia , Ana M Iturregui , Igone Imaz , Claudia Manini , Jorge Garcia-Olaverri , José I López *

In this work Dámaso Parrón and co-authors report a clinical case of unilateral testicular degeneration associated to SARS-CoV-2 infection. Overall the manuscript is well written and goes straight to the point. Few concerns are listed beow. 

1)     The authors state that the spermatic artery displayed an occlusive endothelial proliferation admixed with leukocytes. However, there is no proof. I ask authors to co-stain sections with endothelia and proliferation marker (such as PCNA) to actually show  ongoing proliferation of endothelia cells.

2)     The authors describe that CD4 and CD8 cells were intravascular lymphocytes but they do not provide any evidence. Please, do so.

3)     In figure 2C-D they authors show the IHC for SARS-CoV-2 spike protein. Please show also greater magnifications and add a negative control to show antibody specificity.

4)     In figure 2E-F, are shown EM images of viral particles. Please stain section using immunogold technique to proof are SARS-CoV-2 viral particles. 5)     The authors don’t mention any problem associated with right testicle and spermatic cord even not in the discussion. Was integrity of these organs analyzed with non-invasive or minimally invasive technique? Is there any hypothesis that can be done on why the infraction should be unilateral?

Author Response

The authors thank the reviewer's comments.

1. We do not use PCNA as a marker of endothelium. The occlusive lesion in the spermatic cord artery is advanced, with fibrosis. so no primitive endothelial are there any more. Instead, the reparative process is compsed, as expected, of fibroblasts and scarce inflammatory cells. Any immunohistochemistry here would not be informative at this last stage of the lesion.
2. We performed immunohistochemistry to detect possible predonimance of T cells in the inflammatory infiltrates. Since both B and T were there present, we have not considered informative any picture showing both subpopulations
3. Yes, the picture with the immunostaining with SARS-CoV-2 antibody has been enlarged. In addition, a negative control in the same slide has been included in figure 2.
4. We do not have immuno-electron microscopy technology with gold.
5. Right testicle was not damaged and this sentence has been included in the text. Since there is no previous references to unilateral testicular involvement by SARS-CoV-2 infection, any physiopathological argument based only in one case seems ellucubrative. The interest of this case is just to communicate to physicians in general and urologists in particular, that a massive acute testicular infarction may be another manifestation of Covid-19 infection. We have also added in the text that, apparently, no other organ has been affectad.

Reviewer 3 Report

SARS-CoV-2-associated obliterative arteritis causing massive testicular infarction

(Case Report)

Clinpract- 1170328

In the present work, authors describe a clinical case of massive testicular infarctation associated to SARS-CoV-2 infection. Although the condition itself is not so rare, or significative to merit a publication of a case report, the fact that it described in the context of a SARS-CoV-2 infection brings novelty and considerable interest to the work. Also, it is an actual topic with application in the present global context.

The methods used in the approach of the clinical case were appropriate and robust, in both diagnosis pre-surgery situation and after orquiectomy.  The description is written in an appropriate mode and conclusions are interesting to the readers of Clinics and Practice. Globally, the work provides an advance in this topic and is relevant in the actual pandemic context.

I have minor suggestions.

L41: please refer the correct measures of the testicle excised, as 8 cm belong to length, height or width? Additionally, provide information on its volume and the measures of the contralateral testicle.

Figure 1- It is rather difficult to identify that it is a Doppler ultrasound, as there is no scale of colours (or size, as well). As presented, it seems more a B-Mode ultrasound rather than a Doppler given the absence of Doppler sign in the infarcted testicle. Maybe the comparison with a Figure of Doppler evaluation of the normal testis could be appropriate, if there is record of that.

Finally, histological images should have a scale-bar.

Author Response

We thank the reviewer's comments.

1. Lenght of the surgical specimen and size of the testis have been included in the description.
2. A doppler figure has been added instead of the previous one. Additionally, a picture of the surgical specimen taken at the surgery room has been added to Figure 1.
3. Instead of including a scale bar in such different augmentations in Figure 2, we have included in the text the original magnification information, that is also an alternative way to reflect a scale.

Reviewer 4 Report

The authors describe a very interesting case of SARS-CoV-2-associated obliterative arteritis causing massive 2 testicular infarction, which could be improved after revision.

Abstract: provides a fair summary of the article

There are few major comments:

-Covid-19 is associated with coagulopathy. Could you please provide information regarding D-dimers, PT/aPTT and fibrinogen levels?

-Please also report if patient presented vasculitis in other organs.

-Covid-19 vasculitis has been reported mainly in severely ill patients. Have you tried any of the proposed treatments in your patients (steroids,anticoagulants?)

-Please also report how the patients was treated for his Covid-19 before obliterative arteritis presentation.

Minor comments:

The manuscript will require only  minor copy editing during production to formalize the English.

Author Response

The authros thank the reviewer's comments.

1. There was not coagulopathy in any moment of the clinical course (added in the text). Coagulation pattern was absolutely within the normal limits.
2. No signs or symptoms of vasculitis were detected elsewhere (added in the text).
3. Since the patient had very mild manifestation of Covid-19 infection, only symptomatic treatment was instaured. Corticoids were administered after left orchiectomy as a preventive attitude.
4. Minor changes in the English have been included throughout the text.

Round 2

Reviewer 2 Report

I am fine with the current version of the manuscript.