Identification of a Novel Susceptibility Marker for SARS-CoV-2 Infection in Human Subjects and Risk Mitigation with a Clinically Approved JAK Inhibitor in Human/Mouse Cells

Coronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020; www.who.int ) . While fatality rates are higher among the elderly and those with underlying comorbidities , host factors that promote susceptibility t...

Full description

Saved in:
Bibliographic Details
Published inbioRxiv
Main Authors Spalinger, Marianne R, Hai, Rong, Li, Jiang, Santos, Alina N, Nordgren, Tara M, Tremblay, Michel L, Eckmann, Lars, Hanson, Elaine, Scharl, Michael, Wu, Xiwei, Boland, Brigid S, McCole, Declan F
Format Journal Article Paper
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 09.12.2020
Cold Spring Harbor Laboratory
Edition1.1
Subjects
ACE2
Angiotensin-converting enzyme 2
Coronaviruses
COVID-19
Inflammatory diseases
Microbiology
PTPN2 protein
Severe acute respiratory syndrome coronavirus 2
Spike protein
Susceptibility
Viral infections
COVID-19
SARS-CoV-2
Coronavirus
Tofacitinib
Inflammatory Bowel Disease
genetic susceptibility
autoimmune disease
Online AccessGet full text

Cover

More Information
Summary:Coronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020; www.who.int ) . While fatality rates are higher among the elderly and those with underlying comorbidities , host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases. We report that the autoimmune risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry mediated by SARS-CoV-2 spike protein. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib. Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk.
Bibliography:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
Competing Interest Statement: BSB consulted for Pfizer Inc, unrelated to the content of this article. DFM has received investigator-initiated research awards from the makers of tofacitinib (Pfizer Inc.) through the ASPIRE-Pfizer JAK-STAT in IBD Research Program for studies unrelated to the content of this manuscript.
ISSN:2692-8205
2692-8205
DOI:10.1101/2020.12.09.416586