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

J Infect Dis. 2021 Mar 3;223(5):752-764. doi: 10.1093/infdis/jiab039.


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.

Keywords: COVID-19; SARS-CoV-2; autopsy; in situ hybridization; replication.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autopsy
  • COVID-19 / complications
  • COVID-19 / virology*
  • COVID-19 Nucleic Acid Testing
  • Child
  • Child, Preschool
  • Endothelium, Vascular / virology*
  • Female
  • Humans
  • In Situ Hybridization
  • Infant
  • Lung / virology
  • Male
  • Middle Aged
  • RNA, Viral / isolation & purification
  • Real-Time Polymerase Chain Reaction
  • Respiratory System / virology*
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / physiology*
  • Viral Tropism
  • Virus Replication*
  • Whole Genome Sequencing
  • Young Adult


  • RNA, Viral