WEBINAR: Lecture series in Infection & Immunity - "Genetic and immunological causes of life-threatening COVID-19" - Prof Jean-Laurent Casanova
26/03/2021 16:00 to 26/03/2021 17:15 (Europe/Luxembourg)
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, inter-individual 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.
About the Lecture & Workshop series - Infection & Immunity
The LIH Lecture Series and Workshops in Infection and Immunity, supported by the FNR, are gathering internationally recognised speakers to address topics around Infection and Immunity. Lectures will be organised, followed by workshops especially dedicated to early-stage researchers.
Attendance to the lectures and workshops are free of charge. Should you be interested in registering for the workshops, please feel free to do so by sending us an email.