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Review 2: "Histopathological assessments reveal retinal vascular changes, inflammation, and gliosis in patients with lethal COVID-19"

This preprint provides an in situ analysis of retinal tissue and suggests that there are severe subclinical abnormalities that could be detected in the eyes of covid-19 positive patients. The relevance of these findings in in-vivo evaluation among COVID-19 patients is needed.

Published onApr 18, 2021
Review 2: "Histopathological assessments reveal retinal vascular changes, inflammation, and gliosis in patients with lethal COVID-19"
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key-enterThis Pub is a Review of
Histopathological assessments reveal retinal vascular changes, inflammation and gliosis in patients with lethal COVID-19
Description

ABSTRACTPurposeTo assess for histopathological changes within the retina and the choroid and determine the long-term sequelae of the SARS-CoV-2 infection.DesignComparative analysis of human eyes.SubjectsEleven donor eyes from COVID-19 positive donors and similar age-matched donor eyes from patients with a negative test for SARS-CoV-2 were assessed.MethodsGlobes were evaluated ex-vivo with macroscopic, SLO and OCT imaging. Macula and peripheral regions were processed for epon-embedding and immunocytochemistryMain Outcome MeasuresRetinal thickness and histopathology, detection of SARS-CoV-2 Spike protein, changes in vascular density, gliosis, and degree of inflammation.ResultsFundus analysis shows hemorrhagic spots and increased vitreous debris in several of the COVID-19 eyes compared to the control. OCT based measurements indicated an increased trend in retinal thickness in the COVID-19 eyes, however the difference was not statistically significant. Histology of the retina showed presence of hemorrhages and central cystoid degeneration in several of the donors. Whole mount analysis of the retina labeled with markers showed changes in retinal microvasculature, increased inflammation, and gliosis in the COVID-19 eyes compared to the controls. The choroidal vasculature displayed localized changes in density and signs of increased inflammation in the COVID-19 samples.ConclusionsIn situ analysis of the retinal tissue suggested that there are severe subclinical abnormalities that could be detected in the COVID-19 eyes. This study provides a rationale for evaluating the ocular physiology of patients that have recovered from COVID-19 infections to further understand the long-term effects caused by this virus.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

In the current document, Dr. Vijay K. Jidigam and colleagues (1) have evaluated a major concern about COVID-19, which is the risk for long-term consequences after infection. For this purpose, they have performed a comparative analysis of human eyes in an elegant ex-vivo evaluation of macroscopic (SLO and OCT imaging) and microscopic (epon-embedding and immunocytochemistry) case-control study. They have confirmed the presence of retinal changes described in several other reports in the macroscopic evaluation of the retina, and their document adds a microscopic description of COVID-19-related retinal derangement. Their findings justify with strong evidence their main conclusion and intention, which is to provide a rationale for evaluating the ocular physiology of patients that have recovered from COVID-19 to further understand the long-term effects caused by this virus. The retina is an accessible proxy for the central nervous system and Cotton wool exudates are a marker of vascular disease severity in other medical contexts, such as diabetes and hypertension, and are associated with an increased risk for acute vascular events not restricted to patients who complain of visual symptoms.

To date, COVID-19 has affected more than 120 million people worldwide (2), and universal screening for asymptomatic consequences seems unfeasible. An additional argument in favor of their approach is that not all COVID-19 infected subjects develop neurologic or visual symptoms, but among most severe cases, with pneumonia, the global pre-test probability (2 to 30%) might possibly be more accurately defined to about 20% (3), information that could be included in the manuscript. Whether COVID-19 acts synergistically with other diseases, such as diabetes, accelerating the neuro-ophthalmic vascular disease still requires further evaluation. The relevance of the in-vivo retinal evaluation is the possibility of identifying a population at risk that deserves a close follow-up. Most COVID-19 infected patients recover with no identifiable short-term consequences, but the long-term repercussions of the infection are obviously unknown, especially considering the structural damage described in the current report. A non-invasive risk stratification might be a cost-effective strategy to select a subset of patients who deserve a close follow-up to promote preventive strategies (i.e. healthy lifestyle intervention) and/or early treatment of obesity and/or diabetes. Therefore, I recommend the acceptance of the document, with only the aforementioned minor suggestion, that is not even a concern.

 

References:

 1.       Jidigam VK, Singh R, Batoki JC, Milliner C, Sawant OB, Bonilha VL, et al. Running head: Vascular and inflammatory changes in patients with lethal COVID-19. medRxiv [Internet]. 2021 Feb 28 [cited 2021 Mar 19];2021.02.25.21251531. Available from: https://doi.org/10.1101/2021.02.25.21251531

2.        COVID-19 Map - Johns Hopkins Coronavirus Resource Center [Internet]. [cited 2021 Mar 19]. Available from: https://coronavirus.jhu.edu/map.html

3.        Landecho MF, Yuste JR, Gándara E, Sunsundegui P, Quiroga J, Alcaide AB, et al. COVID-19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease? J Intern Med [Internet]. 2021 Jan 1 [cited 2021 Mar 19];289(1):116–20. Available from: https://pubmed.ncbi.nlm.nih.gov/32729633/

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