Evidence of Severe Acute Respiratory Syndrome Coronavirus 2 Replication and Tropism in the Lungs, Airways, and Vascular Endothelium of Patients With Fatal Coronavirus Disease 2019: An Autopsy Case Series

Autor: Jana M. Ritter, Yan Li, Anna Uehara, Brooke Leitgeb, Christopher D. Paddock, Roosecelis B Martines, Sherif R. Zaki, Joy Gary, Amy M. Denison, Lindsey B.C. Estetter, Suxiang Tong, Clinton R. Paden, Sarah Reagan-Steiner, Elizabeth Lee, Julu Bhatnagar, Ying Tao, Marlene DeLeon-Carnes, Wun-Ju Shieh, Timothy M. Uyeki
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Pathology
Respiratory System
medicine.disease_cause
Virus Replication
Pathogenesis
0302 clinical medicine
Immunology and Allergy
030212 general & internal medicine
Child
Lung
Cellular localization
In Situ Hybridization
Coronavirus
Aged
80 and over
virus diseases
Middle Aged
medicine.anatomical_structure
AcademicSubjects/MED00290
Infectious Diseases
COVID-19 Nucleic Acid Testing
Child
Preschool
RNA
Viral
Female
Adult
medicine.medical_specialty
replication
Adolescent
In situ hybridization
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Young Adult
autopsy
medicine
Major Article
Humans
Tropism
Aged
Whole Genome Sequencing
business.industry
SARS-CoV-2
COVID-19
Infant
Viral Tropism
030104 developmental biology
Viral replication
Tissue tropism
Endothelium
Vascular
business
Zdroj: The Journal of Infectious Diseases
ISSN: 1537-6613
0022-1899
DOI: 10.1093/infdis/jiab039
Popis: 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 severe acute respiratory syndrome coronavirus 2 (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; 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. Results SARS-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. 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.
By analyzing tissues from patients with fatal COVID-19, using in situ hybridization and RT-PCR, we identified cellular targets of SARS-CoV-2 tropism and replication in the lungs, airways, and vascular endothelium. These findings provide important insights into COVID-19 pathogenesis and severe outcomes.
Databáze: OpenAIRE
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