Characterization of SARS-CoV-2 and host entry factors distribution in a COVID-19 autopsy series

SARS-CoV-2 is a highly contagious virus that causes the disease COVID-19. We have recently reported that androgens regulate the expression of SARS-CoV-2 host entry factors ACE2 and TMPRSS2, and androgen receptor (AR) in lung epithelial cells. We also demonstrated that the transcriptional repression of the AR enhanceosome inhibited SARS-CoV-2 infection in vitro. To better understand the various sites of SARS-CoV-2 infection, and presence of host entry factors, we extensively characterized the tissue distribution and localization of SARS-CoV-2 virus, viral replication, and host entry factors in various anatomical sites sampled via autopsy. We applied RNA in-situ-hybridization (RNA-ISH), immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) approaches. We also assessed histopathological changes in SARS-CoV-2 infected tissues. We detect SARS-CoV-2 virus and viral replication in pulmonary tissues by RNA-ISH and IHC and a variety of non-pulmonary tissues including kidney, heart, liver, spleen, thyroid, lymph node, prostate, uterus, and colon by qRT-PCR. We observe heterogeneity in viral load and viral cytopathic effects among various organ systems, between individuals and within the same patient. In a patient with a history of kidney transplant and under immunosuppressant therapy, we observe an unusually high viral load in lung tissue by RNA-ISH, IHC and qRT-PCR. SARS-CoV-2 virus is also detected in this patent’s kidney, liver and uterus. We find ACE2, TMPRSS2 and AR expression to overlap with the infection sites. This study portrays the impact of dispersed SARS-CoV-2 infection in diverse organ systems, thereby facilitating avenues for systematic therapeutic approaches. To understand SARS-CoV-2 infection of human organs, we characterized the tissue distribution of SARS-CoV-2 virus, and the presence of host factors that enable the virus to enter cells, in postmortem tissues from six patients who had COVID-19. We assessed the presence of SARS-CoV-2 viral RNA and the expression of human genes that facilitate virus entry in host cells, using several techniques. We observed that SARS-CoV-2, and factors that facilitate virus entry in host cells, were present in the same location in pulmonary and multiple nonpulmonary tissues, including lung, bronchus, trachea, kidney, heart, liver, spleen, thyroid, lymph node, prostate, uterus, and colon. We also reported changes in the microscopic appearance of SARS-CoV-2 infected tissues at various sites. Such findings will guide future coronavirus biology studies on patients with advanced disease. Wang et al. characterize the tissue distribution of SARS-CoV-2 viral infection and replication as well as the expression of host cell entry factors in postmortem samples from six patients with COVID-19. They report the co-existence of SARS-CoV-2 infection and host entry factors in multiple pulmonary and non-pulmonary tissues.