Abstract

The pathogenesis of SARS-CoV-2 remains to be completely understood, and detailed SARS-CoV-2 cellular cytopathic effects requires definition. We performed a comparative ultrastructural study of SARS-CoV-1 and SARS-CoV-2 infection in Vero E6 cells and in lungs from deceased COVID-19 patients. SARS-CoV-2 induces rapid death associated with profound ultrastructural changes in Vero cells. Type II pneumocytes in lung tissue showed prominent altered features with numerous vacuoles and swollen mitochondria with presence of abundant lipid droplets. The accumulation of lipids was the most striking finding we observed in SARS-CoV-2 infected cells, both in vitro and in the lungs of patients, suggesting that lipids can be involved in SARS-CoV-2 pathogenesis. Considering that in most cases, COVID-19 patients show alteration of blood cholesterol and lipoprotein homeostasis, our findings highlight a peculiar important topic that can suggest new approaches for pharmacological treatment to contrast the pathogenicity of SARS-CoV-2.

Highlights

  • Introduction Since the first discovery ofSARS-CoV-2, as a novel human zoonotic pathogen in late December 2019, there have been 1.5 millions of deaths from COVID-19 disease reported by the WHO as of December 2020

  • A striking finding revealed by our study is the presence of numerous lipid droplets induced by SARS-CoV-2 infection, a major difference when compared to SARS-CoV-1 infection

  • Lipid droplets found in SARS-Cov-2 infection, both in vitro and in type II pneumocytes, appear similar to those known to occur in hepatocytes as a consequence of hepatitis C virus (HCV) infection[35]

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Summary

Introduction

Introduction Since the first discovery ofSARS-CoV-2, as a novel human zoonotic pathogen in late December 2019 (ref. 1), there have been 1.5 millions of deaths from COVID-19 disease reported by the WHO as of December 2020 (ref. 2). SARS-CoV-2 infects the host cells using the angiotensin converting enzyme 2 (ACE2) receptor[12], which is expressed in cells and vessels of several organs, including the lung, heart, kidney, and intestine, but ultrastructural studies carried out so far show rather discordant findings concerning the presence of viral particles inside different tissues[13,14,15]. In vitro cytopathic studies of SARS-CoV-2 using cell lines may not capture the in vivo pathology and performing studies in parallel is important. Based on this assumption we performed a comparative ultrastructural study of SARS-CoV-2 infection in Vero E6 cells and lung tissue from patients who died of COVID-19 disease. We investigated the effects of SARS-CoV-2 on Vero cells, compared to effects of SARS-CoV-1

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