Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes
Author(s)
Type
Journal Article
Abstract
SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 post-mortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID post-mortem controls. SARS-CoV-2 anti-NP staining in the post-mortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained post-mortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE-2 expression, the entry receptor for SARS-CoV-2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS-CoV-2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms to the organ tropism of SARS-CoV-2 in contemporary cases as well as providing insights into potential long-term complications of COVID-19. This article is protected by copyright. All rights reserved.
Date Issued
2022-02-02
Date Acceptance
2022-01-29
Citation
Journal of Pathology, 2022, 257 (2)
ISSN
0022-3417
Publisher
Pathological Society of Great Britain and Ireland
Journal / Book Title
Journal of Pathology
Volume
257
Issue
2
Copyright Statement
© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Community Jameel Imperial College COVID-19 Excellence Fund
Imperial College COVID-19 Research Grant
NWLP Research Committee
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35107828
Grant Number
NWLP Research co-ordination grant
Subjects
COVID-19
Enteric nervous system
Gastrointestinal tract
Immunohistochemistry
Megakaryocytes
Myenteric plexus
Neurons
Parkinson's Disease
SARS-CoV-2
Tropism
Publication Status
Published online
Coverage Spatial
England
Date Publish Online
2022-02-02