학술논문
Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes.
Document Type
Academic Journal
Author
Gray-Rodriguez S; Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.; Jensen MP; Department of Cellular Pathology, Northwest London Pathology, Charing Cross Hospital Campus, London, UK.; Otero-Jimenez M; Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.; Hanley B; Department of Cellular Pathology, Northwest London Pathology, Charing Cross Hospital Campus, London, UK.; Department of Immunology and Inflammation, Imperial College London, London, UK.; Swann OC; Department of Infectious Disease, Imperial College London, London, UK.; Ward PA; Chelsea and Westminster NHS Foundation Trust, London, UK.; Salguero FJ; National Infection Service, United Kingdom Health Security Agency, Salisbury, UK.; Querido N; Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.; Farkas I; Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.; Velentza-Almpani E; Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.; Weir J; Department of Cellular Pathology, Northwest London Pathology, Charing Cross Hospital Campus, London, UK.; Barclay WS; Department of Infectious Disease, Imperial College London, London, UK.; Carroll MW; National Infection Service, United Kingdom Health Security Agency, Salisbury, UK.; Pandemic Sciences Centre, Nuffield Department of Medicine, Oxford University, Oxford, UK.; Jaunmuktane Z; Department of Neuropathology, UCL Queen Square Institute of Neurology, London, UK.; Brandner S; Department of Neuropathology, UCL Queen Square Institute of Neurology, London, UK.; Pohl U; Department of Cellular Pathology, Queen Elizabeth Hospital Birmingham/University Hospitals Birmingham, Birmingham, UK.; Allinson K; Department of Neuropathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Thom M; Department of Neuropathology, UCL Queen Square Institute of Neurology, London, UK.; Troakes C; Basic and Clinical Neuroscience Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; Al-Sarraj S; Basic and Clinical Neuroscience Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.; Sastre M; Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.; Gveric D; Multiple Sclerosis and Parkinson's Tissue Bank, Imperial College London, Hammersmith Hospital, London, UK.; Gentleman S; Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.; Multiple Sclerosis and Parkinson's Tissue Bank, Imperial College London, Hammersmith Hospital, London, UK.; Roufosse C; Department of Cellular Pathology, Northwest London Pathology, Charing Cross Hospital Campus, London, UK.; Department of Immunology and Inflammation, Imperial College London, London, UK.; Osborn M; Department of Cellular Pathology, Northwest London Pathology, Charing Cross Hospital Campus, London, UK.; Alegre-Abarrategui J; Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.; Department of Cellular Pathology, Northwest London Pathology, Charing Cross Hospital Campus, London, UK.; Multiple Sclerosis and Parkinson's Tissue Bank, Imperial College London, Hammersmith Hospital, London, UK.
Source
Publisher: John Wiley And Sons Country of Publication: England NLM ID: 0204634 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-9896 (Electronic) Linking ISSN: 00223417 NLM ISO Abbreviation: J Pathol Subsets: MEDLINE
Subject
Language
English
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 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. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
(© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
(© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)