Broad Severe Acute Respiratory Syndrome Coronavirus 2 Cell Tropism and Immunopathology in Lung Tissues From Fatal Coronavirus Disease 2019
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Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
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SciScore for 10.1101/2020.09.25.20195818: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: All autopsies were performed with written consent from the legal next-of-kin, and specimens were obtained per the Autopsy Service protocol.
IRB: Specimens obtained at autopsy do not meet the definition of a living individual per Federal Regulations 45 CFR 46.102, and as such, research using specimens obtained at autopsy does not meet the requirements for Institutional Review Board review or oversight under the Icahn School of Medicine Program for the Protection of Human Subjects.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable COVID-19 lung tissue samples: Anonymized postmortem specimens were … SciScore for 10.1101/2020.09.25.20195818: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: All autopsies were performed with written consent from the legal next-of-kin, and specimens were obtained per the Autopsy Service protocol.
IRB: Specimens obtained at autopsy do not meet the definition of a living individual per Federal Regulations 45 CFR 46.102, and as such, research using specimens obtained at autopsy does not meet the requirements for Institutional Review Board review or oversight under the Icahn School of Medicine Program for the Protection of Human Subjects.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable COVID-19 lung tissue samples: Anonymized postmortem specimens were collected from five adults (4 male and 1 female) with fatal SARS-CoV-2 infection by the Autopsy Service of the Department of Pathology, Molecular and Cell-based Medicine at the Icahn School of Medicine at Mount Sinai. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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