Tissue-based SARS-CoV-2 detection in fatal COVID-19 infections: Sustained direct viral-induced damage is not necessary to drive disease progression.
COVID-19
Coronavirus
Diffuse alveolar damage
Nucleoprotein
RNA in situ hybridization
SARS-CoV-2
Spike protein
Journal
Human pathology
ISSN: 1532-8392
Titre abrégé: Hum Pathol
Pays: United States
ID NLM: 9421547
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
15
03
2021
revised:
23
04
2021
accepted:
28
04
2021
pubmed:
8
5
2021
medline:
18
8
2021
entrez:
7
5
2021
Statut:
ppublish
Résumé
Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although viral infection is known to trigger inflammatory processes contributing to tissue injury and organ failure, it is unclear whether direct viral damage is needed to sustain cellular injury. An understanding of pathogenic mechanisms has been handicapped by the absence of optimized methods to visualize the presence and distribution of SARS-CoV-2 in damaged tissues. We first developed a positive control cell line (Vero E6) to validate SARS-CoV-2 detection assays. We then evaluated multiple organs (lungs, kidneys, heart, liver, brain, intestines, lymph nodes, and spleen) from fourteen COVID-19 autopsy cases using immunohistochemistry (IHC) for the spike and the nucleoprotein proteins, and RNA in situ hybridization (RNA ISH) for the spike protein mRNA. Tissue detection assays were compared with quantitative polymerase chain reaction (qPCR)-based detection. SARS-CoV-2 was histologically detected in the Vero E6 positive cell line control, 1 of 14 (7%) lungs, and none (0%) of the other 59 organs. There was perfect concordance between the IHC and RNA ISH results. qPCR confirmed high viral load in the SARS-CoV-2 ISH-positive lung tissue, and absent or low viral load in all ISH-negative tissues. In patients who die of COVID-19-related organ failure, SARS-CoV-2 is largely not detectable using tissue-based assays. Even in lungs showing widespread injury, SARS-CoV-2 viral RNA or proteins were detected in only a small minority of cases. This observation supports the concept that viral infection is primarily a trigger for multiple-organ pathogenic proinflammatory responses. Direct viral tissue damage is a transient phenomenon that is generally not sustained throughout disease progression.
Identifiants
pubmed: 33961839
pii: S0046-8177(21)00070-8
doi: 10.1016/j.humpath.2021.04.012
pmc: PMC8095022
pii:
doi:
Substances chimiques
RNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110-119Subventions
Organisme : NINDS NIH HHS
ID : R01 NS106229
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142733
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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