Abstract
BackgroundSARS-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.MethodsTo 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.ResultsWe 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.ConclusionsThis study portrays the impact of dispersed SARS-CoV-2 infection in diverse organ systems, thereby facilitating avenues for systematic therapeutic approaches.
Highlights
Background severe acute respiratory syndrome (SARS)CoV-2 is a highly contagious virus that causes the disease COVID-19
In our recent study detailing transcriptional regulation of SARS-CoV-2 entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), we described co-expression of the androgen receptor (AR), TMPRSS2, and ACE2 in bronchial and alveolar cells in human and murine lung tissues; demonstrated that androgens regulate the expression of ACE2, TMPRSS2, and AR in subpopulations of lung epithelial cells; and reported that transcriptional repression of the AR enhanceosome by AR antagonists inhibited SARS-CoV2 infection in vitro[8]
All patients exhibited abnormal pulmonary findings on radiologic imaging including the presence of ground-glass opacities on computed tomography (CT)
Summary
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. Results 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. 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 qRTPCR. Six patients with SARS-CoV-2 infection who died from COVID-19 disease with clinical autopsies performed at Michigan Medicine were included in the study. All the patients tested positive for SARS-CoV-2 by quantitative reverse transcription polymerase chain reaction (qRT-PCR) performed in a clinical laboratory. For the purposes of this study, representative FFPE tissue blocks (n = 74) were selected from 16 different anatomical sites by two pathologists Mehra) based on the evaluation of hematoxylin and eosin (H&E) stained FFPE slides with brightfield microscopy
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