Multiorgan and Vascular Tropism of SARS-CoV-2

Cédric Hartard,Nicla Settembre,Sergueï Malikov,Elodie Marchand,Laurent Martrille,Isabelle Koscinski,Duc Trung Nguyen,Ahlam Chaqroun,Evelyne Schvoerer,Benjamin Lefevre,Charles Mazeaud,Guillaume Gauchotte

doi:10.3390/v14030515

Abstract

Although the respiratory tract is the main target of SARS-CoV-2, other tissues and organs are permissive to the infection. In this report, we investigated this wide-spectrum tropism by studying the SARS-CoV-2 genetic intra-host variability in multiple tissues. The virological and histological investigation of multiple specimens from a post-mortem COVID-19 patient was performed. SARS-CoV-2 genome was detected in several tissues, including the lower respiratory system, cardio-vascular biopsies, stomach, pancreas, adrenal gland, mediastinal ganglion and testicles. Subgenomic RNA transcripts were also detected, in favor of an active viral replication, especially in testicles. Ultra-deep sequencing allowed us to highlight several SARS-CoV-2 mutations according to tissue distribution. More specifically, mutations of the spike protein, i.e., V341A (18.3%), E654 (44%) and H655R (30.8%), were detected in the inferior vena cava. SARS-CoV-2 variability can contribute to heterogeneous distributions of viral quasispecies, which may affect the COVID-19 pathogeny.

Highlights

SARS-CoV-2, causing coronavirus disease 2019 (COVID-19), was detected for the first time in December 2019
A mild perivascular lymphocytic infiltrate was observed in the myocardium, without cardiomyocytes alteration
This variability must be considered within viruses multiplying in the same individual as a viral quasispecies, which could determine, at least partially, the tissue tropism

Summary

Introduction

SARS-CoV-2, causing coronavirus disease 2019 (COVID-19), was detected for the first time in December 2019. Since this new pathogen has rapidly spread, with more than 300 million of infected people worldwide and more than 5 million of deaths. The clinical signs involve mainly the respiratory tract and the subsequent complication results in an acute respiratory distress syndrome (ARDS). As the COVID-19 pandemic continues to progress, knowledge about its wide-spectrum clinical manifestations and associated complications is advancing. Other organs failures are reported, such as cardiovascular involvement, with the description of myocarditis, vascular endothelial injury or thromboembolic events [1–3]. The presence of the SARS-CoV-2 genome has already been reported outside the respiratory tract, most notably in the kidney, gastrointestinal system, nervous system and blood vessels, with some arguments in favor of a local replication [5–11]

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Conclusion