NIH VideoCast - Genetic Studies Illuminating Pathways Important for Controlling COVID Disease

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Genetic Studies Illuminating Pathways Important for Controlling COVID Disease

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Air date:	Thursday, December 3, 2020, 12:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 909 (543 Live, 366 On-demand)
Category:	COVID-19
Runtime:	01:01:52
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	COVID-19 Scientific Interest Group Dr. Su is chief of the Human Immunological Diseases Section in the NIAIDS Laboratory of Clinical Immunology & Microbiology. Her lab strives to understand the molecular mechanisms regulating the human immune system and how their derangements cause disease, with the objective of improving diagnosis and treatment. Her lab studies patients with a spectrum of poorly characterized, inherited immunodeficiencies and autoimmune diseases who lack molecular diagnoses. Dr. Su is particularly interested in combined immunodeficiencies that lead to susceptibility to viral infections and the new biological insights that studying these patients can provide. Lecture summary: Only a small proportion of people who become infected with SARS-CoV-2 become critically ill. Understanding the genetic determinants underlying such outcomes is the goal of our laboratory, in collaboration with the NIAID COVID-19 Consortium and the COVID Human Genetic Effort. Since monogenic inborn errors of immunity can underlie susceptibility to respiratory viruses, we hypothesized that critical COVID-19 disease can similarly reflect an inborn error of immunity. We found that rare genetic variants impacting the type I IFN signaling pathway were associated with life-threatening disease. Functional studies in several showed impaired ability to produce type I IFN and restrict SARS-CoV-2 replication in vitro, which could be restored by the wild-type gene. Importantly, some patients without such genetic lesions instead had neutralizing autoantibodies against type I IFNs. These autoantibodies were highly potent and capable of abolishing protection against SARS-CoV-2 replication in vitro. Together, inherited and acquired defects in the type I IFN pathway accounted for up to ~150f critically ill COVID-19 patients in our cohort. These results underscore the importance of type I IFNs in host immunity against SARS-CoV-2 infection and suggest this pathway as a potential target for therapeutic intervention.

NLM Title:	Genetic studies illuminating pathways important for controlling COVID disease / Helen Su ; COVID-19 Scientific Interest Group.
Author:	Su, Helen. National Institutes of Health (U.S.). COVID-19 Scientific Interest Group,
Publisher:
Abstract:	(CIT): COVID-19 Scientific Interest Group Dr. Su is chief of the Human Immunological Diseases Section in the NIAIDS Laboratory of Clinical Immunology & Microbiology. Her lab strives to understand the molecular mechanisms regulating the human immune system and how their derangements cause disease, with the objective of improving diagnosis and treatment. Her lab studies patients with a spectrum of poorly characterized, inherited immunodeficiencies and autoimmune diseases who lack molecular diagnoses. Dr. Su is particularly interested in combined immunodeficiencies that lead to susceptibility to viral infections and the new biological insights that studying these patients can provide. Lecture summary: Only a small proportion of people who become infected with SARS-CoV-2 become critically ill. Understanding the genetic determinants underlying such outcomes is the goal of our laboratory, in collaboration with the NIAID COVID-19 Consortium and the COVID Human Genetic Effort. Since monogenic inborn errors of immunity can underlie susceptibility to respiratory viruses, we hypothesized that critical COVID-19 disease can similarly reflect an inborn error of immunity. We found that rare genetic variants impacting the type I IFN signaling pathway were associated with life-threatening disease. Functional studies in several showed impaired ability to produce type I IFN and restrict SARS-CoV-2 replication in vitro, which could be restored by the wild-type gene. Importantly, some patients without such genetic lesions instead had neutralizing autoantibodies against type I IFNs. These autoantibodies were highly potent and capable of abolishing protection against SARS-CoV-2 replication in vitro. Together, inherited and acquired defects in the type I IFN pathway accounted for up to 150f critically ill COVID-19 patients in our cohort. These results underscore the importance of type I IFNs in host immunity against SARS-CoV-2 infection and suggest this pathway as a potential target for therapeutic intervention.
Subjects:	COVID-19--etiology COVID-19--genetics COVID-19--immunology
Publication Types:	Lecture Webcast

NLM Classification:	WC 506.3
NLM ID:	101774303
CIT Live ID:	38875
Permanent link:	https://videocast.nih.gov/watch=38875

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