• Julu Bhatnagar, Joy Gary, Sarah Reagan-Steiner, Lindsey B Estetter, Suxiang Tong, Ying Tao, Amy M Denison, Elizabeth Lee, Marlene DeLeon-Carnes, Yan Li, Anna Uehara, Clinton R Paden, Brooke Leitgeb, Timothy M Uyeki, Roosecelis B Martines, Jana M Ritter, Christopher D Paddock, Wun-Ju Shieh, and Sherif R Zaki.
• Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
• J. Infect. Dis. 2021 Mar 3; 223 (5): 752-764.

BackgroundThe 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and replication in various tissues.MethodsWe evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case patients (age range, 1 month to 84 years; 21 COVID-19 confirmed, 43 suspected COVID-19) by SARS-CoV-2 reverse-transcription polymerase chain reaction (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.ResultsSARS-CoV-2 was identified by RT-PCR in 32 case patients (21 COVID-19 confirmed, 11 suspected). 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 endothelial cells and vessel walls of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. The D614G variant was detected in 9 RT-PCR-positive case patients.ConclusionsWe 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.Published by Oxford University Press for the Infectious Diseases Society of America 2021.

39 keywords...

hide…