"COVID endothelioteca" in testing the hypothesis of induction of genome instability by the SARS-CoV-2 virus in the endothelium of patients who have recovered from COVID-19

Abstract

Background. Since viruses are capable of destabilizing the genomes of somatic cells in cell populations infected by them, we put forward a hypothesis about the possible induction of genome instability in the endothelium in patients who have recovered from COVID-19 and its prognostic significance.

The aim of the study was to test the hypothesis that the SARS-CoV-2 virus penetrates endothelial cells and can induce genomic instability in them, which persists in those who have recovered from COVID-19.

Materials and methods. To test the hypothesis, the CROSS-SECTION study was conducted in several clinics in St. Petersburg in the period from 2021-2023. During this period, we collected and stored a bank of biopsy specimens and cytological preparations with endothelial cells from 51 patients who had a new coronavirus infection (COVID+) and 43 patients not infected with SARS-CoV-2 (COVID–). We called the material recorded and stored with information support during the specified period of the COVID-19 pandemic “covid endotheliosis,” which we use to test hypotheses of the pathogenesis of the new coronavirus infection, conducting retrospective laboratory (cytopathological) studies. As an indicator of the induction of genomic instability in the endothelium, we selected micronuclei (MN) and internuclear chromosomal bridges (CB) in interphase endotheliocytes in cytological preparations obtained from removed hemorrhoids during hemorrhoidectomy during the COVID-19 pandemic.

Results. Over 70% of cells in the cytograms of hemorrhoids were represented by CD31+ endothelial cells. A study of more than 45,000 endothelial cells conducted in the “COVID+” group of patients who had suffered a new coronavirus infection and in the “COVID-” group who did not have COVID-19 did not reveal a single case of detection of a micronucleus or internuclear chromosome bridge. Thus, all 94 patients had indicators “MY–” and “HM–”.

The χ-square criterion, which we calculated to test the hypothesis about the relationship between the “COVID+” indicator and the “MY+” and “HM+” indicators, was equal to 0.68 ((df = 1, p = 0.409).

Conclusion. The hypothesis put forward about the induction of genome instability in the endothelium by the SARS-CoV-2 virus in patients who have recovered from COVID-19 was not confirmed. Apparently, the expected effect of SARS-Cov-2 on systemic endotheliopathy (outside the lungs and heart) in COVID-19 is reversible and the typical pathophysiological reactions that cause “long Covid” are overestimated.