Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients
Dickson W. L. Wong,
Barbara M. Klinkhammer,
Sonja Djudjaj,
Sophia Villwock,
M. Cherelle Timm,
Eva M. Buhl,
Sophie Wucherpfennig,
Claudio Cacchi,
Till Braunschweig,
Ruth Knüchel-Clarke,
Danny Jonigk,
Christopher Werlein,
Roman D. Bülow,
Edgar Dahl,
Saskia von Stillfried,
Peter Boor
Affiliations
Dickson W. L. Wong
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Barbara M. Klinkhammer
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Sonja Djudjaj
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Sophia Villwock
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
M. Cherelle Timm
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Eva M. Buhl
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Sophie Wucherpfennig
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Claudio Cacchi
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Till Braunschweig
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Ruth Knüchel-Clarke
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Danny Jonigk
Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany
Christopher Werlein
Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 30625 Hannover, Germany
Roman D. Bülow
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Edgar Dahl
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Saskia von Stillfried
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Peter Boor
Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
Multiorgan tropism of SARS-CoV-2 has previously been shown for several major organs. 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.
