Target Health Blog

Genetic and Immunologic Factors of Some Cases of Severe COVID-19

November 2, 2020

,
Immunology
Source:

New findings by scientists at the National Institutes of Health and their collaborators help explain why some people with COVID-19 develop severe disease. The findings also may provide the first molecular explanation for why more men than women die from COVID-19.

Th following results are the first published results from the COVID Human Genetic Effort, it was found that more than 10% of people who develop severe COVID-19 have misguided antibodies -- autoantibodies -- that attack the immune system rather than the virus that causes the disease. In addition, another 3.5% or more of people who develop severe COVID-19 carry a specific kind of genetic mutation that impacts immunity. Consequently, both groups lack effective immune responses that depend on type I interferon, a set of 17 proteins crucial for protecting cells and the body from viruses. Whether these proteins have been neutralized by autoantibodies or -- because of a faulty gene -- were produced in insufficient amounts or induced an inadequate antiviral response, their absence appears to be a commonality among a subgroup of people who suffer from life-threatening COVID-19 pneumonia.

For the study, the authors discovered 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 influenza virus, and more than 3.5% were completely missing a functioning gene. Further experiments showed that immune cells from those 3.5% did not produce any detectable type I interferons in response to SARS-CoV-2. Examining nearly 1,000 patients with life-threatening COVID-19 pneumonia, the authors also found that more than 10% had autoantibodies against interferons at the onset of their infection, and 95% of those patients were men. Biochemical experiments confirmed that the autoantibodies block the activity of interferon type I.

References:

Q Zhang et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science DOI: 10.1126/science.abd4570 (2020).

P Bastard et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science DOI: 10.1126/science.abd4585 (2020).

Source: NIH

Contact Target Health

Reach out today and let us know how we can help you!
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form