دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes
المؤلفون: 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
المصدر: Journal of Pathology (2022) (In press).
بيانات النشر: Wiley
سنة النشر: 2022
المجموعة: University College London: UCL Discovery
مصطلحات موضوعية: COVID-19, Enteric nervous system, Gastrointestinal tract, Immunohistochemistry, Megakaryocytes, Myenteric plexus, Neurons, Parkinson's Disease, SARS-CoV-2, Tropism
الوصف: 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 ...
نوع الوثيقة: article in journal/newspaper
وصف الملف: text
اللغة: English
العلاقة: https://discovery.ucl.ac.uk/id/eprint/10143744/1/The%20Journal%20of%20Pathology%20-%202022%20-%20Gray%E2%80%90Rodriguez%20-%20Multisystem%20screening%20reveals%20SARS%E2%80%90CoV%E2%80%902%20in%20neurons%20of%20the%20myenteric.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10143744Test/
الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10143744/1/The%20Journal%20of%20Pathology%20-%202022%20-%20Gray%E2%80%90Rodriguez%20-%20Multisystem%20screening%20reveals%20SARS%E2%80%90CoV%E2%80%902%20in%20neurons%20of%20the%20myenteric.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10143744Test/
حقوق: open
رقم الانضمام: edsbas.14FA7AB8
قاعدة البيانات: BASE