Gray-Rodriguez, Sandra; Jensen, Melanie P; Otero-Jimenez, Maria; Hanley, Brian; Swann, Olivia C; Ward, Patrick A; Salguero, Francisco J; ... Alegre-Abarrategui, Javier; + view all Gray-Rodriguez, Sandra; Jensen, Melanie P; Otero-Jimenez, Maria; Hanley, Brian; Swann, Olivia C; Ward, Patrick A; Salguero, Francisco J; Querido, Nadira; Farkas, Ildiko; Velentza-Almpani, Elisavet; Weir, Justin; Barclay, Wendy S; Carroll, Miles W; Jaunmuktane, Zane; Brandner, Sebastian; Pohl, Ute; Allinson, Kieren; Thom, Maria; Troakes, Claire; Al-Sarraj, Safa; Sastre, Magdalena; Gveric, Djordje; Gentleman, Steve; Roufosse, Candice; Osborn, Michael; Alegre-Abarrategui, Javier; - view fewer (2022) Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes. Journal of Pathology 10.1002/path.5878. (In press).

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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.

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