COVID-19: Autoantibodies Can Cause Severe Disease and Deaths

The human body's defence mechanism, the immune system, becomes alert the moment a virus successfully enters it. As a reaction, the immune system activates a complex matrix of reactions and produces a variety of molecules, all directed at clearing off the virus. Antibodies, primarily proteins, are the most known type of immune molecules; an extremely important weapon as they carry the ability to kill the virus.

Despite all their abilities to protect the human body from various types of foreign attacks, antibodies could also attack a body's own cells, thereby, doing more harm than benefits. There are antibodies that often turn against elements of the immune system rather than the virus. These antibodies have proven to be a key driver of severe illness and in some cases, even deaths, amongst people infected with Covid-19.

Known as autoantibodies, they have led to a number of severe Covid-related deaths, as per an international study. Autoantibodies may also be present in a small proportion in healthy and uninfected people, with their prevalence increasing with age.

The findings reported recently in Science Immunology, provide strong evidence of autoantibodies causing disease severity in Covid-19 patients. The study was led by Jean-Laurent Casanova of the Rockefeller University, New York. The same team had reported about the autoantibodies and their association with Covid-19 in October last year, in a study published in Science. In that research, Casanova’s team had found that about 10% of the people who developed severe Covid-19 had autoantibodies that target and block a particular type of immune system molecule, the type-1 interferon. Type-1 interferons play a pivotal role in fighting off infections caused by viruses.

Aaron Ring, an immunologist at the Yale School of Medicine, who was not involved with the two studies mentioned above, was quoted in Nature as saying, “The initial report from last year was probably one of the most important papers in the pandemic. What they’ve done in this new study is really dig down to see just how common these antibodies are across the general population — and it turns out they’re astonishingly prevalent.”

In the latest study, the researchers focused on detecting autoantibodies that neutralize interferons. They incorporated 3595 patients from 38 countries that were critical cases of Covid-19, i.e. the patients required ICU admission at some point in their recovery. The study found that over 13.6% of these patients contained autoantibodies. Interestingly, this proportion also varied age-wise; 9.6% were found to be below the age of 40, while 21% were found to be above the age of 80. The team also found that over 18% of the deceased patients also contained autoantibodies.

Casanova’s team speculated that the rogue antibodies are a cause of disease severity and deaths rather than a consequence of critical Covid-19. They had hinted at a similar finding in their paper published in October, wherein, they had reported that the autoantibodies were present in 4 out of 1000 healthy people whose samples were collected before the pandemic. The team, in their other studies, also found that people having genetic mutations that can affect the activity of type-1 interferons are at a higher risk of a life-threatening disease.

To further examine this correlation, the team conducted a search of autoantibodies in healthy people before the pandemic and collected blood samples from 35,000 healthy people. They found that 0.18% of the people in the age group between 18 to 69 years had autoantibodies that can target type-1 interferons. The study also revealed that autoantibodies concentration in a human body increased with age.

Explaining the increase of autoantibodies with age and Covid-19 severity, Casanova commented, “There is a massive increase in prevalence with age. This largely explains the high risk of severe COVID in people in the elderly population.”

Aaron Ring noted that a sample of over 30,000 people can't be simply ignored. “It just shows that this is something that we need to think about, ” he said.

Casanova’s findings bear significant implications from a clinical point of view. Hospitals need to tune themselves in detecting the autoantibodies for a proper prognosis of disease severity in people.

In a different study, Ring’s team has also found autoantibodies that target various components of the immune system amongst people with Covid-19. The team plans to investigate the matter further in future studies.