Coronavirus can distort the body’s defenses in several ways – disarming the body’s early warning systems, for example, or causing immune cells to fail. But a flurry of new studies suggests another insidious consequence: the infection can trigger the production of antibodies that wrongly attack the patient’s own tissues instead of the virus.
The latest report, published online this week, suggests that so-called autoantibodies may persist for months after the infection resolves, perhaps causing irreparable damage. If other studies confirm the finding, this may explain some of the persistent symptoms in people who have recovered from Covid-19. The syndrome, sometimes called Covidonga long, can include dementia, “brain fog” and joint pain.
Autoantibodies are not new to science: they are the mistaken soldiers of the immune system, linked to debilitating diseases like lupus and rheumatoid arthritis, which arise when the body attacks its own tissues.
The most recent study is small, with only nine patients, five of whom had autoantibodies for at least seven months. It has not yet been submitted to peer review for publication and the authors recommended caution in interpreting the results.
“It’s a sign; it is not definitive, ”said Dr. Nahid Bhadelia, medical director of the special pathogen unit at Boston Medical Center, who led the study. “We don’t know what its prevalence is and whether or not it may be linked to Covid Long.”
The issue of autoimmunity after coronavirus infection is urgent and important, added Dr. Bhadelia. Up to one in three Covid-19 survivors say they still have symptoms.
“This is a real phenomenon,” she said. “We are facing a second pandemic of people with potential continuing disabilities who may not be able to return to work, and this has a major impact on health systems.”
A growing body of evidence suggests that autoimmunity contributes to the severity of Covid-19 in some people. A study published online in October found that among 52 patients with severe Covid-19, more than 70 percent carried antibodies against their own DNA and against proteins that aid in blood clotting.
In another study, also published online in October, the researchers found autoantibodies to carbohydrates produced by the body in patients with Covid-19, which could explain the neurological symptoms. And a study in the journal Science Translational Medicine in November found that half of the patients hospitalized for Covid-19 had at least transient autoantibodies that cause blood clots and blockages.
The combined research raises the worrying possibility that persistent autoantibodies can lead to autoimmune disease in some people infected with the coronavirus.
“Once these autoantibodies are induced, there is no going back,” said Akiko Iwasaki, an immunologist at Yale University. “They will be a permanent part of the person’s immune system.”
She added: “What does that do with the vaccine response? What does this do with newly acquired infections? All of these are questions that will have to be answered ”.
Dr. Iwasaki’s team showed in December that critically ill patients had dramatic increases in a wide range of autoantibodies that target parts of the immune system, brain cells, connective tissue and clotting factors.
“We really do see responses of largely reactive autoantibodies in these patients,” said Dr. Iwasaki. She suspected that autoimmunity might play a role, but “not even I expected to see so much auto-reactivity.”
Dr. Iwasaki and her colleagues collected blood from 172 patients with a variety of symptoms, 22 healthcare workers who had been infected and 30 uninfected healthcare workers.
One in five infected patients had autoantibodies for five proteins in their own bodies and up to 80% for at least one protein, the researchers found. Patients with severe Covid-19 had many more of these antibodies, which impaired their immune responses and worsened the disease. Of the 15 patients who died during the study, 14 had autoantibodies to at least one constituent of the immune system.
The study convincingly shows that autoantibodies “alter the course of the disease,” said Marion Pepper, an immunologist at the University of Washington in Seattle who was not involved in the research.
Autoimmunity after illness is not exclusive to the coronavirus. Other intensely inflammatory infections, including malaria, leprosy and respiratory viruses, are also known to trigger autoantibodies. But autoimmunity and Covid-19 can be a particularly dangerous mix, experts say.
An analysis of nearly 170,000 people with rare autoimmune rheumatic diseases, such as lupus and scleroderma, indicated that they face greater chances of death from Covid-19. And a study of more than 130,000 people found that autoimmune diseases like type 1 diabetes, psoriasis and rheumatoid arthritis increase the risk of respiratory complications and death from Covid-19.
Some of the antibodies appeared to be the result of innate defects in the immune system. For example, a study published in the journal Science in October found that about 10% of Covid-19’s critically ill patients had autoantibodies that attacked key components of the immune system that were supposed to take action after exposure to the virus. Without this quick response, the body’s defense is hopelessly delayed, fighting a losing battle against the multiplying virus.
However, the mere presence of autoantibodies does not indicate damage. They are in the general population and do not always cause disease, noted some experts.
“Anywhere from 10 to 15 percent of the population has some level of auto-reactivity,” said Dr. Iñaki Sanz, an immunologist at Emory University. “The problem is that you need many other events downstream of autoantibodies to induce the disease.”
At least in some patients, autoantibodies clearly emerged as a result of the disease, Dr. Iwasaki’s study showed. Extreme inflammation caused by viral infections can cause cells to open, expelling their contents and confusing the immune system’s ability to distinguish the “me” from the “other”.
But autoantibodies induced in this way can stabilize after a few months, said Dr. Shiv Pillai, an immunologist at Harvard University: “Probably in the vast majority of patients with Covid-19, autoantibodies appear in the acute phase and then decrease.”
“That said – yes, it would be interesting if long Covid could be explained by specific autoantibodies,” he added.
Several researchers, including Dr. Bhadelia and Dr. Iwasaki, are following patients over time to see how long autoantibodies persist and whether they cause permanent damage. Although scientists know that acute infections can trigger their presence, the phenomenon has never been studied in such detail.
“This is perhaps the only silver lining here,” said Pepper. “We are going to learn some fundamental principles about acute viral infections in people who were not easy to study in this way before.”