Persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of advanced COVID-19 pathology.
Aged
Aged, 80 and over
Alveolar Epithelial Cells
/ cytology
Autopsy
Betacoronavirus
/ genetics
COVID-19
Coronavirus Infections
/ complications
Critical Care
Endothelial Cells
/ virology
Female
Giant Cells
/ cytology
Humans
Lung
/ pathology
Male
Pandemics
Pneumonia, Viral
/ complications
RNA, Viral
/ metabolism
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ metabolism
Thrombosis
/ etiology
COVID-19
Endothelial dysfunction
Post-mortem analysis
SARS-CoV-2
Spike protein
Syncytia
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
23
09
2020
revised:
08
10
2020
accepted:
15
10
2020
pubmed:
8
11
2020
medline:
26
11
2020
entrez:
7
11
2020
Statut:
ppublish
Résumé
COVID-19 is a deadly pulmonary disease with peculiar characteristics, which include variable clinical course and thrombophilia. A thorough understanding of the pathological correlates of the disease is still missing. Here we report the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. Histological analysis is complemented by immunohistochemistry for cellular and viral antigens and the detection of viral genomes by in situ RNA hybridization. COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%). Thrombi were in different stages of organization, consistent with their local origin. Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease. An additional feature was the common presence of a large number of dysmorphic pneumocytes, often forming syncytial elements (36/41, 87%). Despite occasional detection of virus-positive cells, no overt signs of viral infection were detected in other organs, which showed non-specific alterations. COVID-19 is a unique disease characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia. Several of COVID-19 features might be consequent to the persistence of virus-infected cells for the duration of the disease. This work was supported by a King's Together Rapid COVID-19 Call grant from King's College London. MG is supported by the European Research Council (ERC) Advanced Grant 787971 "CuRE" and by Programme Grant RG/19/11/34633 from the British Heart Foundation.
Sections du résumé
BACKGROUND
BACKGROUND
COVID-19 is a deadly pulmonary disease with peculiar characteristics, which include variable clinical course and thrombophilia. A thorough understanding of the pathological correlates of the disease is still missing.
METHODS
METHODS
Here we report the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. Histological analysis is complemented by immunohistochemistry for cellular and viral antigens and the detection of viral genomes by in situ RNA hybridization.
FINDINGS
RESULTS
COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%). Thrombi were in different stages of organization, consistent with their local origin. Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease. An additional feature was the common presence of a large number of dysmorphic pneumocytes, often forming syncytial elements (36/41, 87%). Despite occasional detection of virus-positive cells, no overt signs of viral infection were detected in other organs, which showed non-specific alterations.
INTERPRETATION
CONCLUSIONS
COVID-19 is a unique disease characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia. Several of COVID-19 features might be consequent to the persistence of virus-infected cells for the duration of the disease.
FUNDING
BACKGROUND
This work was supported by a King's Together Rapid COVID-19 Call grant from King's College London. MG is supported by the European Research Council (ERC) Advanced Grant 787971 "CuRE" and by Programme Grant RG/19/11/34633 from the British Heart Foundation.
Identifiants
pubmed: 33158808
pii: S2352-3964(20)30480-1
doi: 10.1016/j.ebiom.2020.103104
pmc: PMC7677597
pii:
doi:
Substances chimiques
RNA, Viral
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103104Subventions
Organisme : European Research Council
ID : 787971
Pays : International
Organisme : British Heart Foundation
ID : RG/19/11/34633
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no conflict of interest.
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