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The new findings from scientists at the National Institutes of Health and their collaborators help explain why some people with COVID-19 develop serious illness. The findings may also provide the first molecular explanation for why more men than women die from COVID-19.
The researchers found that more than 10% of people who develop severe COVID-19 have misdirected antibodies (autoantibodies) that attack the immune system rather than the virus that causes the disease. Another 3.5% or more of people who develop severe COVID-19 carry a specific type of gene mutation that affects immunity. Consequently, both groups lack effective immune responses that depend on type I interferon, a set of 17 proteins crucial to protecting cells and the body from viruses. Whether these proteins have been neutralized by autoantibodies or, due to a faulty gene, were produced in insufficient quantities or induced an inadequate antiviral response, their absence appears to be a common feature among a subset of people with life-threatening COVID-19 pneumonia. .
These findings are the first published results of the COVID Human Genetic Effort, an international project spanning more than 50 genetic sequencing centers and hundreds of hospitals. The effort is co-led by Helen Su, MD, Ph.D., principal investigator at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH; and Jean-Laurent Casanova, MD, Ph.D., director of the St. Giles Laboratory of Human Genetics of Infectious Diseases at the Rockefeller University in New York. The main contributions were made by Luigi Notarangelo, MD, chief of the Laboratory of Clinical Immunology and Microbiology at NIAID (LCIM); Steven Holland, MD, director of the NIAID Division of Intramural Research and principal investigator of the NIAID LCIM; doctors and researchers in hospitals in the Italian cities of Brescia, Monza and Pavia, which were severely affected by COVID-19; and researchers from the Uniformed Services University of Health Sciences in Bethesda, Maryland.
The wide variation in the severity of disease caused by SARS-CoV-2, the virus behind COVID-19, has puzzled scientists and clinicians. SARS-CoV-2 can cause anything from infection with no symptoms to death, with many different results in between. Since February 2020, Drs. Su and Casanova and their collaborators have enrolled thousands of COVID-19 patients to find out if a genetic factor drives these disparate clinical outcomes.
Researchers found that among nearly 660 people with severe COVID-19, a significant number carried rare genetic variants in 13 genes known to be critical in the body’s defense against the influenza virus, and more than 3.5% were completely lacking. of a functional gene. . Other experiments showed that immune cells in that 3.5% did not produce detectable type I interferons in response to SARS-CoV-2.
Examining nearly 1,000 patients with life-threatening COVID-19 pneumonia, the researchers also found that more than 10% had autoantibodies against interferons at the onset of infection, and 95% of those patients were men. Biochemical experiments confirmed that autoantibodies block the activity of type I interferon.
Article
Q Zhang et al. Inborn Errors of Type I IFN Immunity in Life-threatening COVID-19 Patients. Sciences DOI: 10.1126 / science.abd4570 (2020).
P Bastard et al. Autoantibodies against IFN type I in patients with life-threatening COVID-19. Sciences DOI: 10.1126 / science.abd4585 (2020).
who
NIAID Director Anthony S. Fauci, MD, NIAID Principal Investigator Helen C. Su, MD, Ph.D., and Luigi Notarangelo, MD, chief of NIAID’s Laboratory of Clinical Immunology and Microbiology, are available to interviews.
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To schedule interviews, contact the NIAID Office of Communications, (301) 402-1663, [email protected].
Does NIAID conduct and support research? at the NIH, in the United States, and around the world? study the causes of infectious and immune-mediated diseases, and develop better means to prevent, diagnose and treat these diseases. NIAID-related press releases, fact sheets, and other materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services.The NIH is the primary federal agency conducting and supporting basic, clinical, and medical research. translational, and is researching causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.
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