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- Title
Broad Severe Acute Respiratory Syndrome Coronavirus 2 Cell Tropism and Immunopathology in Lung Tissues From Fatal Coronavirus Disease 2019.
- Authors
Silva, Suzane Ramos da; Ju, Enguo; Meng, Wen; Mondolfi, Alberto E Paniz; Dacic, Sanja; Green, Anthony; Bryce, Clare; Grimes, Zachary; Fowkes, Mary; Sordillo, Emilia M; Cordon-Cardo, Carlos; Guo, Haitao; Gao, Shou-Jiang; Ramos da Silva, Suzane; Paniz Mondolfi, Alberto E
- Abstract
<bold>Background: </bold>Coronavirus disease 2019 (COVID-19) patients manifest with pulmonary symptoms reflected by diffuse alveolar damage (DAD), excessive inflammation, and thromboembolism. The mechanisms mediating these processes remain unclear.<bold>Methods: </bold>We performed multicolor staining for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and lineage markers to define viral tropism and lung pathobiology in 5 autopsy cases.<bold>Results: </bold>Lung parenchyma showed severe DAD with thromboemboli. Viral infection was found in an extensive range of cells including pneumocyte type II, ciliated, goblet, club-like, and endothelial cells. More than 90% of infiltrating immune cells were positive for viral proteins including macrophages, monocytes, neutrophils, natural killer (NK) cells, B cells, and T cells. Most but not all infected cells were angiotensin-converting enzyme 2 (ACE2) positive. The numbers of infected and ACE2-positive cells are associated with extensive tissue damage. Infected tissues exhibited high levels of inflammatory cells including macrophages, monocytes, neutrophils, and NK cells, and low levels of B cells but abundant T cells consisting of mainly T helper cells, few cytotoxic T cells, and no regulatory T cells. Robust interleukin-6 expression was present in most cells, with or without infection.<bold>Conclusions: </bold>In fatal COVID-19 lungs, there are broad SARS-CoV-2 cell tropisms, extensive infiltrated innate immune cells, and activation and depletion of adaptive immune cells, contributing to severe tissue damage, thromboemboli, excess inflammation, and compromised immune responses.
- Subjects
COVID-19; REGULATORY T cells; T helper cells; KILLER cells; CYTOTOXIC T cells
- Publication
Journal of Infectious Diseases, 2021, Vol 223, Issue 11, p1842
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiab195