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Characterization of SARS-CoV-2 and host entry factors distribution in a COVID-19 autopsy series.
Wang, Xiao-Ming; Mannan, Rahul; Xiao, Lanbo; Abdulfatah, Eman; Qiao, Yuanyuan; Farver, Carol; Myers, Jeffrey L; Zelenka-Wang, Sylvia; McMurry, Lisa; Su, Fengyun; Wang, Rui; Pantanowitz, Liron; Jentzen, Jeffrey; Wilson, Allecia; Zhang, Yuping; Cao, Xuhong; Chinnaiyan, Arul M; Mehra, Rohit.
  • Wang XM; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Mannan R; Michigan Center for Translational Pathology, Ann Arbor, MI USA.
  • Xiao L; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Abdulfatah E; Michigan Center for Translational Pathology, Ann Arbor, MI USA.
  • Qiao Y; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Farver C; Michigan Center for Translational Pathology, Ann Arbor, MI USA.
  • Myers JL; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Zelenka-Wang S; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • McMurry L; Michigan Center for Translational Pathology, Ann Arbor, MI USA.
  • Su F; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Wang R; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Pantanowitz L; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Jentzen J; Michigan Center for Translational Pathology, Ann Arbor, MI USA.
  • Wilson A; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Zhang Y; Michigan Center for Translational Pathology, Ann Arbor, MI USA.
  • Cao X; Michigan Center for Translational Pathology, Ann Arbor, MI USA.
  • Chinnaiyan AM; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
  • Mehra R; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
Commun Med (Lond) ; 1: 24, 2021.
Article in English | MEDLINE | ID: covidwho-1860411
ABSTRACT

Background:

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.

Methods:

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.

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. 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.

Conclusions:

This study portrays the impact of dispersed SARS-CoV-2 infection in diverse organ systems, thereby facilitating avenues for systematic therapeutic approaches.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Systematic review/Meta Analysis Language: English Journal: Commun Med (Lond) Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Systematic review/Meta Analysis Language: English Journal: Commun Med (Lond) Year: 2021 Document Type: Article