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A significant proportion of patients who develop life-threatening forms of Covid-19 have genetic or immunological defects that impair their ability to fight the virus, research has found. In papers published in the journal Science, the Covid Human Genetic Effort international consortium describes two glitches in severely ill Covid-19 patients that prevent them from making a frontline immune molecule called type 1 interferon. The patients would have carried these glitches for years before the pandemic, or in the case of the genetic errors, all their lives. The discovery may help to explain a mystery surrounding the coronavirus: why it leaves some sufferers sick or dying in intensive care, while others remain barely affected or asymptomatic. The consortium sequenced all or part of the genomes of 659 severely ill Covid-19 patients from around the world, as well as those of 534 people with asymptomatic or mild infection, and found that the severely ill patients were more likely to carry a type of mutation leaving them unable to make interferon. Though each such mutation is rare, collectively they occurred in 3. 5% of severe cases. In the second study, involving nearly 1,000 severe Covid-19 patients, they found at least one in 10 patients carried antibodies to their own interferon, which block its action. No such auto-antibodies were found in asymptomatic or mild patients, and they were detected in only a tiny fraction (0. 3%) of healthy controls. These findings were described by one scientist as astonishing. Together, the two types of error account for about 15% of life-threatening Covid-19 cases, according to the immunologist Jean-Laurent Casanova of the Rockefeller University in New York City and the Necker Hospital for Sick Children in Paris, who co-directs the consortium. Casanova suspects human genetics will end up explaining the majority of such cases, however, because the consortium has only looked for mutations in 13 of the 300-odd type 1 interferon-related
