In an international study in Science, 10 percent of nearly 1,000 COVID patients who developed life-threatening pneumonia had antibodies that disable key immune system proteins called interferons, reported Kaiser Health News.
These antibodies — known as autoantibodies because they attack the body itself — were not found at all in 663 people with mild or asymptomatic COVID infections. Only four of 1,227 healthy individuals had the autoantibodies. The study was led by the COVID Human Genetic Effort, which includes 200 research centers in 40 countries.
“This is one of the most important things we’ve learned about the immune system since the start of the pandemic,” said Dr. Eric Topol, executive vice president for research at Scripps Research in San Diego, who was not involved in the new study. “This is a breakthrough finding.”
In a second Science study by the same team, authors found that an additional 3.5 percent of critically ill patients had mutations in genes that control the interferons involved in fighting viruses. Given that the body has 500 to 600 of these genes, it’s possible researchers will find more mutations, said Qian Zhang, lead author of the second study.
Interferons serve as the body’s first line of defense against infection, sounding the alarm and activating an army of virus-fighting genes, said virologist Angela Rasmussen, an associate research scientist at the Center of Infection and Immunity at Columbia University’s Mailman School of Public Health.
“Interferons are like a fire alarm and a sprinkler system all in one,” said Rasmussen, who wasn’t involved in the new studies.
Lab studies show interferons are suppressed in some people with COVID-19, perhaps by the virus itself.
Interferons are particularly important for protecting the body against new viruses, such as the coronavirus, which the body has never encountered, said Zhang, a researcher at Rockefeller University’s St. Giles Laboratory of Human Genetics of Infectious Diseases.
When infected with the novel coronavirus, “your body should have alarms ringing everywhere,” said Zhang. “If you don’t get the alarm out, you could have viruses everywhere in large numbers.”
Significantly, patients didn’t make autoantibodies in response to the virus. Instead, they appeared to have had them before the pandemic even began, said Paul Bastard, the antibody study’s lead author, also a researcher at Rockefeller University.
For reasons that researchers don’t understand, the autoantibodies never caused a problem until patients were infected with COVID-19, Bastard said. Somehow, the novel coronavirus, or the immune response it triggered, appears to have set them in motion.
“Before COVID, their condition was silent,” Bastard said. “Most of them hadn’t gotten sick before.”
Bastard said he now wonders whether autoantibodies against interferon also increase the risk from other viruses, such as influenza. Among patients in his study, “some of them had gotten flu in the past, and we’re looking to see if the autoantibodies could have had an effect on flu.”
Scientists have long known that viruses and the immune system compete in a sort of arms race, with viruses evolving ways to evade the immune system and even suppress its response, said Sabra Klein, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health.
Antibodies are usually the heroes of the immune system, defending the body against viruses and other threats. But sometimes, in a phenomenon known as autoimmune disease, the immune system appears confused and creates autoantibodies. This occurs in diseases such as rheumatoid arthritis, when antibodies attack the joints, and Type 1 diabetes, in which the immune system attacks insulin-producing cells in the pancreas.
Dr. Megan Ranney, an associate professor of emergency medicine at Brown University, says that even after months of treating emergency room patients with COVID-19 she doesn’t know what makes certain patients so much sicker than others.
Although doctors don’t know the exact causes of autoimmune disease, they’ve observed that the conditions often occur after a viral infection. Autoimmune diseases are more common as people age.
In yet another unexpected finding, 94 percent of patients in the study with these autoantibodies were men. About 12.5 percent of men with life-threatening COVID pneumonia had autoantibodies against interferon, compared with 2.6 percent of women.
That was unexpected, given that autoimmune disease is far more common in women, Klein said.
“I’ve been studying sex differences in viral infections for 22 years, and I don’t think anybody who studies autoantibodies thought this would be a risk factor for COVID-19,” Klein said. The study might help explain why men are more likely than women to become critically ill with COVID-19 and die, Klein said.
