J Infect Dis . Evidence of SARS-CoV-2 Replication and Tropism in the Lungs, Airways and Vascular Endothelium of Patients with Fatal COVID-19: An Autopsy Case-Series

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J Infect Dis


. 2021 Jan 27;jiab039.
doi: 10.1093/infdis/jiab039. Online ahead of print.
Evidence of SARS-CoV-2 Replication and Tropism in the Lungs, Airways and Vascular Endothelium of Patients with Fatal COVID-19: An Autopsy Case-Series


Julu Bhatnagar ¹ , Joy Gary ¹ , Sarah Reagan-Steiner ¹ , Lindsey B Estetter ¹ , Suxiang Tong ² , Ying Tao ² , Amy M Denison ¹ , Elizabeth Lee ¹ , Marlene DeLeon-Carnes ¹ , Yan Li ² , Anna Uehara ² , Clinton R Paden ² , Brooke Leitgeb ¹ , Timothy M Uyeki ³ , Roosecelis B Martines ¹ , Jana M Ritter ¹ , Christopher D Paddock ¹ , Wun-Ju Shieh ¹ , Sherif R Zaki ¹



Affiliations

• PMID: 33502471
• DOI: 10.1093/infdis/jiab039

Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of SARS-CoV-2 tropism and replication in various tissues.
Methods: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case-patients (age range: 1 month to 84 years; COVID-19 confirmed n=21, suspected n=43) by SARS-CoV-2 RT-PCR. For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in-situ hybridization (ISH), subgenomic RNA RT-PCR, and whole genome sequencing.
Results: SARS-CoV-2 was identified by RT-PCR in 32 case-patients (confirmed n=21 and suspected n=11). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case-patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes and macrophages of lungs, epithelial cells of airways, and in endothelial cells and vessels wall of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. D614G variant was detected in 9 RT-PCR-positive case-patients.
Conclusions: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes.

Keywords: Autopsy; COVID-19; In-situ hybridization; Replication; SARS-CoV-2.