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Courtesy of Matthew Woodruff, Emory University
Around the world, immunologists who remodeled their labs to join the fight against SARS-CoV-2 are furiously trying to explain why some people get so sick while others recover unscathed. The pace is dizzying, but some clear trends have emerged.
One area of interest has been the production of antibodies, powerful proteins capable of disabling and killing invading pathogens such as viruses. The sporadic identification of so-called autoreactive antibodies that, instead of attacking disease-causing microbes, target the tissues of people with severe COVID-19 cases of great concern.
The first studies implicated these autoantibodies in the formation of dangerous blood clots in patients admitted to intensive care. More recently, they have been linked to serious illness by inactivating critical components of viral immune defenses in a significant fraction of critically ill patients.
As an immunologist with the Lowance Center for Human Immunology at Emory University, I have been researching the immune response responsible for producing antibodies in COVID-19. Under the direction of Dr. Ignacio Sanz, our group has previously investigated the immune responses that contribute to the production of autoantibodies in autoimmune disorders such as lupus and, more recently, in severe cases of COVID-19. However, although we were able to characterize the response in COVID-19 patients as autoimmune, we were unable to confirm the production of hidden autoantibodies within their antiviral responses.
Now we can.
In a recently published study awaiting peer review, we describe the alarming finding that in the sickest patients with COVID-19, autoantibody production is common, a finding with potentially great impact on both acute and patient care. in recovering from infection.
Severe infection is related to autoantibody production
Autoantibodies come in “flavors” that are generally associated with specific types of diseases. Lupus patients, for example, will often have antibodies that target their own DNA, the molecules that make up the human genome.
Patients with the autoimmune disorder rheumatoid arthritis are less likely to have these antibodies, but more likely to test positive for rheumatoid factor, that is, antibodies that target other antibodies.
In this study, the Lowance Center group analyzed the medical records of 52 intensive care patients who were diagnosed with COVID-19. None of them had a history of autoimmune disorders. However, they were tested during infection for autoantibodies found in a variety of disorders.
The results are tough. More than half of the 52 patients tested positive for autoantibodies. In patients with the highest levels of C-reactive protein (a marker of inflammation) in their blood, more than two-thirds showed evidence that their immune system was producing antibodies that attacked their own tissue.
While these findings raise concern, there are things that our data does not reveal. Although patients with severe disease clearly show autoantibody responses, the data does not tell us to what extent these autoantibodies contribute to the most severe symptoms of COVID-19.
It could be that a severe viral illness routinely causes autoantibodies to be produced with little consequence; this could be the first time we see it. We also do not know how long autoantibodies last. Our data suggest that they remain relatively stable for a few weeks. But we need follow-up studies to understand whether they routinely persist beyond recovery from infection.
Importantly, we believe that the autoreactive responses we have identified here are specific to SARS-CoV-2 infection; there is no reason to believe that similar results would be expected from vaccination against the virus.
Understand the role of autoantibodies in COVID-19
However, while it is possible that these autoantibodies are benign, or even helpful in an as yet unidentified way, they also may not be. Perhaps these self-directed antibody responses do contribute to the severity of the disease, helping to explain the late onset of severe symptoms in some patients that may be correlated with antibody production.
This could be one reason why treatment with dexamethasone, an immunosuppressant often used to quell “flare-ups” of autoimmune disorders, might be effective in treating patients with the most serious disease. It is also possible that these responses are not short-lived, survive infection, and contribute to the ongoing symptoms now experienced by a growing number of “long-term” COVID-19 patients.
Most worryingly, it is possible that these responses may be self-perpetuating in some patients, resulting in new permanent autoimmune disorders.
My colleagues and I sincerely hope that this is not the case; rather, that the appearance of autoantibodies in these patients is a red herring, a peculiarity of the viral immune response in some patients that will resolve on its own. But we must do better than hope: we must ask the right questions and find the answers. Fortunately, this study also gives us the tools to do so.
Self-reactive antibody test may reveal better treatments
The tests that were carried out in these patients to determine their “self-reactive profile” are not specialized. They are available in most hospital labs across the country. In fact, the two most common antibodies found in these patients, antinuclear antibodies and rheumatoid factor, are detected by routine tests used by rheumatologists.
Our study shows that by looking at just these two autoantibodies and the inflammatory marker’s C-reactive protein, we can identify patients most likely to experience potentially dangerous immune responses that could benefit from more aggressive immune modulation.
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Additionally, self-reactivity testing could help identify patients who could benefit from rheumotological follow-up to monitor recovery, and help us understand whether some long-standing COVID-19 cases could be related to persistent autoantibodies. If so, these patients could respond to the same immunologically directed therapies that have been successful in MIS-C, where autoantibody production has now been documented.
Finally, by evaluating patients immediately after recovery from COVID-19, we can establish baselines and begin to track the possible emergence of new cases of autoimmunity after this terrible disease, and plan early rheumatological intervention if necessary.
Now we have the tools. It’s time to start using them.Matthew Woodruff, Instructor, Lowance Center for Human Immunology, Emory University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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