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More than 10 percent of young, healthy people who develop severe Covid-19 have the wrong antibodies that attack not the virus but the immune system itself, and another 3.5 percent may carry a specific type of genetic mutation, according to a new study. .
The research, published in the journal Science, noted that both groups of patients lack type I interferon, a set of 17 proteins crucial to protecting cells and the body from viruses.
These proteins, according to researchers at Rockefeller University in the USA, are part of intrinsic and innate immunity, are activated before the body produces an antibody response and are known to play an important role in the immediate increase of cell defenses in response to various viruses.
In the case of some severe Covid-19 patients, they said that interferons could be neutralized by the patients’ own antibodies or might not be produced in insufficient quantities due to a faulty gene.
They said the findings help explain why some people develop a much more serious illness than others in their age group, including people who required admission to the hospital’s Intensive Care Unit (ICU) despite being 20 and be free of underlying conditions.
The study results, according to the researchers, may also provide the first molecular explanation for why more men than women die from Covid-19.
“These findings provide compelling evidence that disruption of type I interferon is often the cause of life-threatening Covid-19,” says Jean-Laurent Casanova, co-author of the Rockefeller University study.
“And in theory at least, these interferon problems could be treated with existing drugs and interventions,” Casanova said.
The new coronavirus can cause an infection without symptoms in most people, or it can kill others within a few days.
According to the researchers, unusual susceptibility to certain infectious diseases can be attributed to single gene mutations that affect an individual’s immune response.
In the current research, they genetically analyzed blood samples from more than 650 Covid-19 patients who had been hospitalized for life-threatening pneumonia due to the coronavirus, of which 14 percent had died.
The scientists also included samples from another group of more than 530 people with asymptomatic or benign infection. They initially looked for differences between the two groups in 13 genes that are known to govern the production of type I interferons in the body, which are critical to defense against the influenza virus.
According to the study, a significant number of people with serious illnesses carried rare variants in these 13 genes, and more than three percent of them lacked a functional gene.
From subsequent experiments, they showed that the immune cells of these patients did not produce detectable type I interferons in response to the coronavirus.
The scientists showed that human fibroblast cells with mutations affecting the type I interferon pathway were more vulnerable to the virus, died in greater numbers, and did so at a faster rate than cells without those mutations.
They said that three other infectious diseases caused by mutations affecting an immune signaling protein may also be caused by autoantibodies against that protein.
When examining 987 patients with life-threatening Covid-19 pneumonia, they found that more than 10 percent had autoantibodies against interferons at the onset of infection, and most of them (95 percent) were male.
The researchers confirmed these findings through biochemical experiments that demonstrated that these autoantibodies can effectively slow down the activity of type I interferon.
In some cases, the autoantibodies could be detected in blood samples taken before patients became infected, and in others, they said, they were found in the early stages of infection, before the immune system had time to generate a response.
However, autoantibodies appear to be rare in the general population, the scientists said, adding that only four of the 1,227 randomly selected healthy people had them.
“All of these findings clearly indicate that these autoantibodies are actually the underlying reason why some people become seriously ill, and not the consequence of the infection,” Casanova said.
Scientists believe the findings could point to medical interventions that can help control the severity of the disease. Citing one example, they said that two types of interferons available as drugs and approved for use to treat certain conditions, such as chronic viral hepatitis, could be further investigated for their effectiveness against severe Covid-19.
