Dramatic levels of “friendly fire” from the immune system may drive severe Covid-19 disease and leave patients with “long Covid” – when medical problems persist for a significant time after the virus has been beaten – scientists have said.
Researchers at Yale University found that Covid-19 patients had large numbers of misguided antibodies in their blood that targeted the organs, tissues and the immune system itself, rather than fighting off the invading virus.
The scientists compared immune responses in patients and uninfected people and discovered scores of aberrant antibodies in the former.These blocked antiviral defences, wiped out helpful immune cells, and attacked the body on multiple fronts, from the brain, blood vessels and liver to connective tissue and the gastrointestinal tract.
Further tests revealed that the more “autoantibodies” patients had in their blood, the worse their disease. The Covid-19 patients had more antibodies that had turned on them than people with lupus, an autoimmune disease caused by similar wayward antibodies.
“Covid-19 patients make autoantibodies that actually interfere with immune responses against the virus,” said Aaron Ring, an immunobiologist at Yale and senior author on the study. Numerous other autoantibodies attacked parts of the body that are known to become damaged in those with the disease.
“We certainly believe that these autoantibodies are harmful to patients with Covid-19,” said Ring, adding that the harmful effects may well continue after the infection has abated, leaving patients with longer-lasting medical problems. “Because antibodies can persist for a long time, it’s conceivable that they may contribute to the development of long-Covid diseases,” he said.
Ring partnered with Akiko Iwasaki, a professor of immunobiology at Yale, to screen 194 patients and hospital workers with varying severities of Covid infection for autoantibodies that targeted nearly 3,000 human proteins. Antibodies disable viruses by latching on to proteins on the virus surface, but autoantibodies are the wrong shape and mistakenly bind to proteins that are on, or have been released by, human cells.
Writing in the study, which has yet to be peer reviewed and published in a journal, the scientists describe how Covid patients had “dramatic increases in autoantibody reactivities” compared with 30 healthy hospital workers who did not have the virus. While certain autoantibodies in some patients were apparently present before Covid-19 infection, others appeared and ramped up as the disease progressed.