Two Science papers have revealed that some cases of severe COVID-19 are linked to genetic mutations or attacks on the body's autoantibodies.

!--,2020 / / --- New Coronavirus SARS-CoV-2 causes coronavirus disease (COVID-19) in 2019 and is now raging around the world.
infected with the new coronavirus SARS-CoV-2 may develop symptoms from mild to fatal.
, two new studies suggest that some life-threatening cases can be traced back to weaknesses in the patient's immune system.
at least 3.5 percent of patients with severe COVID-19 had mutations in their antiviral defense genes.
at least 10 percent of severely ill people produce "autoantibodies" that attack the immune system rather than fight the virus.
these findings identify some of the root causes of life-threatening COVID-19.
results were published online September 24, 2020 in the journal Science under the titles "Inborn errors of type I IFN immunity in patients with life-risk COVID-19" and "Auto-antibodies against type I IFNs in patients with life-life-19".
images from Science, 2020, doi:10.1126/science.abd4570.
," said Jean-Laurent Casanova, a researcher at Rockefeller University in the United States and co-author of the two papers, that the observation of these harmful antibodies in so many patients (101 out of 987 patients) was a "startling discovery."
" papers explain for the first time why COVID-19 is so severe in some people, while most others are not infected with the same virus.
the results have direct implications for diagnosis and treatment," Casanova said.
added that if someone's coronavirus test is positive, they should also "absolutely" take autoantibodies tests and, if they do, medical follow-up.
antibodies from the blood may reduce the symptoms of the disease.
the global effort Casanova's research team, in collaboration with clinicians around the world, began recruiting COVID-19 patients for the first time in February this year.
time, they were looking for young people with severe COVID-19 to investigate whether their immune systems might have potential weaknesses, making them particularly vulnerable to the virus.
plan to scan patients' genomes, especially the 13 genes involved in the immune response to flu interferon.
in healthy people, interferon molecules can act as safety systems for the human body.
detect invasive viruses and bacteria and alert them, recruiting other immune defenders to the scene.
Team Casanova has previously identified genetic mutations that impede interferon production and function.
people with these mutations are more likely to be infected with certain pathogens, including those that cause influenza.
the team believes that the similar mutations found in COVID-19 patients may help doctors identify patients at risk of developing forms of severe disease.
, he says, could also point the way for treatment.
March, Casanova's team aimed to recruit 500 patients with severe COVID-19 worldwide.
, they had recruited more than 1,500 people, and now they have more than 3,000.
when the researchers began analyzing patient samples, they began to find harmful mutations in young and old people.
team found that 23 of the 659 patients studied carried genetic defects associated with the production of antiviral interferon.
the researchers speculated that COVID-19 patients would not be able to fight the virus without a complete set of these antiviral defense molecules.
idea inspired a new one.
other severe COVID-19 patients also lack interferon--- but for different reasons.
that perhaps some patients' bodies themselves are destroying these molecules.
like autoimmune diseases such as type 1 diabetes and rheumatoid arthritis, some COVID-19 patients may be producing antibodies that target the human body.
, "It was an epiphany moment for us," Casanova said.
" Casanova team's analysis of 987 life-threatening COVID-19 patients revealed this.
at least 101 patients had autoantibodies targeting various interferon proteins.
, "We said, 'Great,'" Casanova recalls. The researchers found that these autoantibodies block interferon, but they are not present in mild COVID-19 cases.
is an unprecedented discovery," said Isabelle Meyts, a pediatrician at the University Hospital of Leuven in Belgium and co-author of the two papers.
, she helped recruit patients to the study, collect samples and conduct experiments.
test the presence of these antibodies, she said, "you can almost predict who will get serious illness."
" Casanova team found that the vast majority of patients (94 percent) who carried harmful antibodies were men.
men are more likely to develop severe forms of COVID-19, and these findings provide an explanation for this gender difference, meyts said.
Casanova Labs is now looking for the genetic drivers behind these autoantibodies.
said they may be related to mutations on the X chromosome.
mutation may not affect women because they have a second X chromosome to compensate for any defects in the first X chromosome.
but for men who carry only one X chromosome, even small genetic errors can have consequences.
to the future clinically, new research by Casanova's team could change the way doctors and health officials view vaccination distribution strategies and even potential treatments.
For example, a clinical trial may examine whether an infected person carrying autoantibodies benefits from the treatment of one of the 17 interferons not in autoantibodies or plasma separation, a medical method for removing antibodies from a patient's blood.
meyts says neither of these methods may counteract the effects of these harmful antibodies.
addition to current research, Meyt, Casanova and hundreds of other scientists involved in an international coalition called COVID's Human Genetic Efforts are working to understand the second part of the coronavirus mystery.
they were not looking for factors that made patients particularly susceptible to COVID-19 infection, but rather for genetic factors that might be protective.
they are now recruiting from families of patients with severe COVID-19, those exposed to the virus but not suffering from the disease.
s lab is running at full speed," said Casanova, a scientist at the University of The People's Republic of China.
" Reference: 1. Qian Zhang et al. Inborn errors of type I IFN immunity in patients with life-security COVID-19. Science, 2020, doi:10.1126/science.abd4570.2.Paul Bastard et al. Auto-antibodies against type I IFNs in patients with life-security COVID-19. Science, 2020, doi:10.1126/science.abd4585.3.severe Some COVID-19 cases linked to genetic mutations or antibodies that attack the body !-- title.