Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes

Sandra Gray-Rodriguez, Melanie P. Jensen, Maria Otero-Jimenez, Brian Hanley, Olivia C. Swann, Patrick A. Ward, Francisco J. Salguero, Nadira Querido, Ildiko Farkas, Elisavet Velentza-Almpani, Justin Weir, Wendy S. Barclay, Miles W. Carroll, Zane Jaunmuktane, Sebastian Brandner, Ute Pohl, Kieren Allinson, Maria Thom, Claire Troakes, Safa Al-SarrajMagdalena Sastre, Djordje Gveric, Steve Gentleman, Candice Roufosse, Michael Osborn, Javier Alegre-Abarrategui*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
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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 postmortem 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 postmortem controls. SARS-CoV-2 anti-NP staining in the postmortem 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 postmortem 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 ACE2 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 with the organ tropism of SARS-CoV-2 in contemporary cases as well as providing insights into potential long-term complications of COVID-19.

Original languageEnglish
Pages (from-to)198-217
Number of pages20
JournalThe Journal of Pathology
Issue number2
Early online date2 Feb 2022
Publication statusPublished - Jun 2022

Bibliographical note

Funding Information:
The work was funded by the Community Jameel Imperial College Covid-19 Excellence Fund and the North West London Pathology Research Grant Commission. ICHTB is supported by the NIHR Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. JAA has also received funding from the NIHR Imperial Biomedical Research Centre (BRC). MPJ is supported by an NIHR Academic Clinical Fellowship.

Open Access: 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.

Publisher Copyright: © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Citation: Gray-Rodriguez, S., Jensen, M.P., Otero-Jimenez, M., Hanley, B., Swann, O.C., Ward, P.A., Salguero, F.J., Querido, N., Farkas, I., Velentza-Almpani, E., Weir, J., Barclay, W.S., Carroll, M.W., Jaunmuktane, Z., Brandner, S., Pohl, U., Allinson, K., Thom, M., Troakes, C., Al-Sarraj, S., Sastre, M., Gveric, D., Gentleman, S., Roufosse, C., Osborn, M. and Alegre-Abarrategui, J. (2022), Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes. J. Pathol., 257: 198-217.



  • COVID-19
  • Parkinson's Disease
  • SARS-CoV-2
  • enteric nervous system
  • gastrointestinal tract
  • immunohistochemistry
  • megakaryocytes
  • myenteric plexus
  • neurons
  • tropism


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