Coronavirus : do autoimmune diseases lead to severe covid-19 cases?
For a little more than a year, the world has been battling covid-19, and researchers have been relentlessly studying the virus and the disease – yet many mysteries remain: why do some people get sick so much more severely than others?? Why does lung damage sometimes worsen when the body seems to have already overcome the sars cov 2 virus? And what’s behind the multi-organ disease that lasts for months in people with fatigue syndrome after an acute covid illness?? Some of these questions may be answered by the immune system mistakenly turning against the body – a phenomenon known as autoimmunity. A growing number of studies suggest that.
"a lot of evidence fits together," says aaron ring, an immunologist at the yale school of medicine in the u.s. Early in the pandemic, researchers suspected that some people were responding to sars cov-2 infection with an exaggerated immune response. Immune system signaling proteins, cytokines, can rise to dangerous levels, leading to cytokine storms and damage to the body’s own cells. Clinical studies have now shown that some drugs that largely dampen immune activity reduce mortality in critically ill people when given at the right time.
This article is included in spektrum kompakt, long covid – the suffering after corona
However, scientists studying covid-19 are also increasingly pointing to the role of autoantibodies: antibodies that attack either elements of the body’s immune defenses or certain proteins in organs such as the heart. Unlike cytokine storms, which typically cause systemic, short-term problems, autoantibodies are thought to lead to targeted, longer-term damage, says immunologist akiko iwasaki, a ring colleague at yale.
Does predisposition to autoimmune disease play a role??
Healthy people also form autoantibodies, but usually not in large quantities. What’s more, the molecules do not appear to cause damage or attack the immune system most of the time. Yet researchers have evidence that autoantibodies play a role in many infectious diseases.
There are several theories that explain how autoimmunity might arise in covid and other infections. Some people may be predisposed to produce autoantibodies, which then become active during infection. Alternatively, infections could even be the cause for autoantibodies to develop. If researchers understand the connection, they could develop treatments for both the effects of covid and other diseases caused by viruses.
In late september 2020, a group led by jean-laurent casanova of rockefeller university in new york city reported that more than ten percent of 987 people with severe covid-19 had antibodies that attacked and blocked the action of type 1 interferon molecules. These molecules normally help boost the immune response against foreign pathogens. That’s a strikingly high proportion, according to the team, because people’s antibody repertoires are usually very different and not a single subject in the control group had these antibodies. Researchers also saw the antibodies in people before they were infected, so casanova believes some people may be genetically predisposed to produce them. In addition, the autoantibodies occurred more frequently in men than in women – a possible reason why covid appears to affect men more severely.
The first evidence that autoantibodies against interferon could put people at higher risk for infectious diseases was published in 1984. Since then, the evidence has piled up, says casanova. Because of covid, the topic is topical again. "now people understand the problem," he says, "and suddenly they realize that what my lab has been doing for 25 years actually makes quite a bit of sense."
Casanova is currently studying 40,000 people to determine how many of them already have autoantibodies and whether their distribution by age, ancestry and gender matches that of severe covid cases. other research groups support casanova’s hypothesis: iwasaki, ring and others screened 194 patients and hospital staff with varying degrees of covid severity for a wide range of autoantibodies. Her study, published online in december 2020 before peer review, found a higher prevalence of autoantibodies to the immune system in infected people than in uninfected people. They found autoantibodies that attacked B cells and some that attacked interferon.
But this study also suggests that sars-cov-2 could cause the body to produce autoantibodies that attack its own tissues. Some of the infected people had autoantibodies against proteins in their blood vessels, heart and brain. This was particularly interesting in light of the fact that many of the symptoms in patients are associated with these organs. However, it is unclear whether the covid 19 infection caused the body to produce these autoantibodies or whether the infected individuals already had them. Iwasaki plans to study more cases to determine if there is a causal link. This would require taking more blood samples from people who have previously been infected.
Half of covid 19 patients had autoantibodies
Researchers have also found autoantibodies to molecules called phospholipids, says michel goldman, an immunologist at the free university of brussels and former director of the european innovative medicines initiative. the largest such study, published in november 2020, found that 52 percent of 172 people hospitalized with covid-19 had these autoantibodies. "this is really concerning," he says, because some phospholipids are known to play a role in controlling the blood clotting that is often increased in covid-19.
In january 2021, another, previously unreviewed study reported autoantibodies that could be activated by covid-19. David lee, an emergency medicine physician at new york university (NYU), along with NYU microbiologist ana rodriguez and others, analyzed serum samples from 86 people hospitalized with covid-19. You searched for autoantibodies against proteins like annexin A2. This protein helps keep cell membranes stable and thus ensures the integrity of the small blood vessels in the lungs. Researchers found significantly higher average levels of anti-annexin A2 antibodies in people who had died than in people with less severe disease. As in other studies, it is unclear whether these autoantibodies existed before infection with coronavirus.
Autoantibody theory may partly explain why severe symptoms of covid-19 are delayed. If the autoantibodies are caused by the cellular damage and inflammation triggered by the viral infection, as lee and others believe, it would take a few weeks for them to build up in the body. This, says lee, may be why much of the damage to tissues like the lungs doesn’t become apparent until long after symptoms like fever appear. In this way, autoimmunity could be the real culprit behind the fatal course of the disease. "clinicians think, ‘oh, this virus is so deadly, we need to get rid of the virus’.’ but then when you talk to the pathologists, they say, ‘yes, we see all this damage, but we don’t see much virus,’" says lee.
Many infections trigger autoimmune diseases
Over the years, scientists have studied numerous cases in which infections trigger autoimmunity. Some reports suggest that infection with the malaria parasite can cause the body to begin attacking red blood cells, causing anemia. And epstein-barr virus – which causes glandular fever (also known as mononucleosis) – has been linked to dozens of autoimmune diseases, including lupus. the underlying causalities, on the other hand, are difficult to pinpoint: it is almost impossible to show whether the infections are the cause of autoimmune diseases or whether they appear in the body for some other reason, says anish suri, president of cue biopharma, a company in cambridge, massachusetts, that is researching therapies for autoimmunity.
Streptococci are a well known example. If left untreated, the disease, which is caused by the bacterium streptococcus pyogenes is caused, trigger an autoimmune reaction (rheumatic fever) that attacks organs and can lead to permanent heart damage. Other bacteria can also lead to autoimmunity: the stomach bacterium helicobacter pylori can cause a disease called immune thrombocytopenic purpura (ITP), in which the body begins to destroy platelets in the blood. In some people with ITP, treatment with antibiotics against the bacteria improves their immune response H. Pylori platelet count, suggesting the drugs are helping to reverse the autoimmune disease.