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We have comprehensively analyzed 25 different formalin-fixed paraffin-embedded (FFPE) tissues\/organs from autopsies of fatal COVID-19 cases (n = 8), using histopathological assessment, detection of SARS-CoV-2 RNA using polymerase chain reaction and RNA in situ hybridization, viral protein using immunohistochemistry, and virus particles using transmission electron microscopy. SARS-CoV-2 RNA was mainly localized in epithelial cells across all organs. Next to lung, trachea, kidney, heart, or liver, viral RNA was also found in tonsils, salivary glands, oropharynx, thyroid, adrenal gland, testicles, prostate, ovaries, small bowel, lymph nodes, skin and skeletal muscle. Viral RNA was predominantly found in cells expressing ACE2, TMPRSS2, or both. The SARS-CoV-2 replicating RNA was also detected in these organs. Immunohistochemistry and electron microscopy were not suitable for reliable and specific SARS-CoV-2 detection in autopsies. These findings were validated using in situ hybridization on external COVID-19 autopsy samples (n = 9). Apart from the lung, correlation of viral detection and histopathological assessment did not reveal any specific alterations that could be attributed to SARS-CoV-2. In summary, SARS-CoV-2 and its replication could be observed across all organ systems, which co-localizes with ACE2 and TMPRSS2 mainly in epithelial but also in mesenchymal and endothelial cells. Apart from the respiratory tract, no specific (histo-)morphologic alterations could be assigned to the SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3390\/cells10081900","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T12:18:31Z","timestamp":1627388311000},"page":"1900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-2908","authenticated-orcid":false,"given":"Dickson W. L.","family":"Wong","sequence":"first","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1566-7129","authenticated-orcid":false,"given":"Barbara M.","family":"Klinkhammer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Djudjaj","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Villwock","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Cherelle","family":"Timm","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-9228","authenticated-orcid":false,"given":"Eva M.","family":"Buhl","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"},{"name":"Electron Microscopy Facility, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Wucherpfennig","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Cacchi","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9166-2912","authenticated-orcid":false,"given":"Till","family":"Braunschweig","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4987-701X","authenticated-orcid":false,"given":"Ruth","family":"Kn\u00fcchel-Clarke","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-2281","authenticated-orcid":false,"given":"Danny","family":"Jonigk","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Werlein","sequence":"additional","affiliation":[{"name":"Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman D.","family":"B\u00fclow","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8439-7994","authenticated-orcid":false,"given":"Edgar","family":"Dahl","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"von Stillfried","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-4284","authenticated-orcid":false,"given":"Peter","family":"Boor","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"},{"name":"Electron Microscopy Facility, RWTH Aachen University Hospital, 52074 Aachen, Germany"},{"name":"Department of Nephrology and Immunology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cabrera Martimbianco, A.L., Pacheco, R.L., Bagattini, A.M., and Riera, R. 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