Join us for our Hot Topics in Research seminar series. Hear from investigators and trainees showcasing hot research topics on and off the Oak Street campus.

Hot Topics in Research is presented by the BC Children's Hospital Research Themes with the support of the Research Education Team.

Inborn Errors of Immunity to SARS-CoV-2

covid-19 immunity research seminar vancouver

Dr. Jean-Laurent Casanova, MD, PhD 

Professor, The Rockefeller University
Investigator, Howard Hughes Medical Institute
Head, St. Giles Laboratory of Human Genetics of Infectious Diseases
Senior Attending Physician, Rockefeller University Hospital 


Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3-and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection.

By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3-and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Also, interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-a (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro.

These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

 

Schedule & Participation

The seminar is scheduled for Thursday, March 25, 2021 from 10:00 to 11:00 a.m. 

Zoom Link

Meeting ID: 683 8792 2865
Passcode: 4126

 

About the Speaker

Dr. Jean-Laurent Casanova, MD, PhD 
Professor, The Rockefeller University
Investigator, Howard Hughes Medical Institute
Head, St. Giles Laboratory of Human Genetics of Infectious Diseases
Senior Attending Physician, Rockefeller University Hospital 

Website: The Rockefeller University 
COVID Human Genetic Effort
Casanova Lab on Twitter

 

Video Library

public lectures and mini med school watch online vancouverVideo recordings of BCCHR public lectures, presentations and virtual recordings are available online. These may be useful for classes, or of interest to those who are unable to attend events. 

For more information, please contact comm@bcchr.ca.