Imperial College London

ProfessorMagdalenaSastre

Faculty of MedicineDepartment of Brain Sciences

Professor in Molecular Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 6673m.sastre

 
 
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Location

 

406Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gray-Rodriguez:2022:10.1002/path.5878,
author = {Gray-Rodriguez, S and Jensen, MP and Otero-Jimenez, M and Hanley, B and Swann, OC and Ward, PA and Salguero, FJ and Querido, N and Farkas, I and Velentza-Almpani, E and Weir, J and Barclay, WS and Carroll, MW and Jaunmuktane, Z and Brandner, S and Pohl, U and Allinson, K and Thom, M and Troakes, C and Al-Sarraj, S and Sastre, M and Gveric, D and Gentleman, S and Roufosse, C and Osborn, M and Alegre-Abarrategui, J},
doi = {10.1002/path.5878},
journal = {Journal of Pathology},
title = {Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes},
url = {http://dx.doi.org/10.1002/path.5878},
volume = {257},
year = {2022}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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
AU - Gray-Rodriguez,S
AU - Jensen,MP
AU - Otero-Jimenez,M
AU - Hanley,B
AU - Swann,OC
AU - Ward,PA
AU - Salguero,FJ
AU - Querido,N
AU - Farkas,I
AU - Velentza-Almpani,E
AU - Weir,J
AU - Barclay,WS
AU - Carroll,MW
AU - Jaunmuktane,Z
AU - Brandner,S
AU - Pohl,U
AU - Allinson,K
AU - Thom,M
AU - Troakes,C
AU - Al-Sarraj,S
AU - Sastre,M
AU - Gveric,D
AU - Gentleman,S
AU - Roufosse,C
AU - Osborn,M
AU - Alegre-Abarrategui,J
DO - 10.1002/path.5878
PY - 2022///
SN - 0022-3417
TI - Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes
T2 - Journal of Pathology
UR - http://dx.doi.org/10.1002/path.5878
UR - https://www.ncbi.nlm.nih.gov/pubmed/35107828
UR - https://onlinelibrary.wiley.com/doi/10.1002/path.5878
UR - http://hdl.handle.net/10044/1/94458
VL - 257
ER -