One area of focus has been the production of antibodies – potent proteins capable of neutralizing and killing invading pathogens such as viruses. A major concern has been the sporadic detection of so-called autoactive antibodies that target tissues of individuals suffering from severe cases of COVID-19, rather than targeting disease-causing microbes.
Early studies implicated these autoinhibitions in dangerous blood clots formed in patients admitted to intensive care. Recently, they have been associated with critical illness by inactivating important components of viral immune protection in a significant fraction of patients with severe disease.
As an immunologist at the Lotion Center for Human Immunology at Emery University, I am investigating the immune response responsible for the production of antibodies to COVID-19. Dr. Under the direction of Ignacius Sanzha, our group has previously investigated immune responses contributing to autoimmune production such as lupus in autoimmune disorders and more recently COVID-19 in severe cases.
However, when we were able to characterize the response as autoimmune in COVID-19 patients, we could not confirm the production of autoantibodies hidden within their antiviral responses.
Now we can.
In a newly released study awaiting peer-review, we describe the startling finding that in the sickest patients with COVID-19, the production of autoantibodies is common – large potential effects on both acute patient care and infection recovery. with.
Severe infection is associated with autoantibody production
Autoantibodies come in “tastes” that are usually associated with specific disease types. For example, lupus patients often have antibodies that target their DNA – the molecules that make up the human genome.
Patients with autoimmune disorder rheumatoid arthritis are less likely to have those antibodies, but more likely to show positive tests for the rheumatoid factor – antibodies that target other antibodies.
In this study, the Lovens Center group analyzed medical charts of 52 patients in intensive care 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 wide variety of disorders.
The results stagger. 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 the blood, more than two-thirds showed evidence that their immune system was producing antibodies attacking their own tissue.
While these findings raise concern, there are things that do not reveal our data. Although patients with critical illness clearly exhibit autoimmune responses, the data do not tell us to what extent these autoantibodies contribute to the most severe symptoms of COVID-19.
It may be that severe viral disease routinely results in the production of autoantibodies with little consequence; This may be the first time we are seeing this. We don’t even know how long the autoinbodies last. Our data suggest that they are relatively stable over a few weeks. However, we need follow-up studies to understand whether they are beyond the recovery of infection.
Importantly, we believe that the autoreactive responses we have identified are specific for SARS-CoV-2 infection – there is no reason to believe that a similar result is expected through vaccination against the virus Will.
Understanding the role of autoantibodies in COVID-19
However, while it is possible that these autoantibodies are benign, or still helpful in a yet unknown manner, it is also possible that they are not. Perhaps these self-targeted antibody responses actually contribute to the severity of the disease, helping to explain the delayed onset of severe symptoms in some patients that may be correlated with antibody production.
This may be one reason why treatment with dexamethasone, an immunosuppressant that is often used to “flare up” autoimmune disorders, can only be effective in treating patients with the most severe disease. It is also possible that these reactions are not short-term, eliminating infection and contributing to ongoing symptoms, now experiencing an increasing number of “long-haler” COVID-19 patients.
At most, it is possible that these reactions can self-destruct in some patients, resulting in new, permanent autoimmune disorders.
My colleagues and I sincerely hope that this is not the case – rather, that the emergence of autoantibodies in these patients is a red herring, a quirk of a viral immune response in some patients that will resolve on its own.
But we need to do better than expected – we need to ask the right questions and know the answers. Fortunately, this study also gives us the tools to do so.
Autoreactive antibody test may reveal better treatment
The tests conducted to determine their “autoreactive profile” on these patients are not specific. They are available in most hospital laboratories across the country.
In fact, the two most common antibodies that we find in these patients, antinuclear antibodies and rheumatoid factors, are detected by common tests used by rheumatologists.
Our study suggests that just by testing these two autoantibodies and the inflammatory marker C-reactive protein, we may be able to identify patients experiencing potentially dangerous immune responses that benefit from more aggressive immune modulation. Can.
In addition, autoreactivity testing can help identify patients who may benefit from rheumatological follow-up to monitor recovery, and help us understand whether “long-hauler” COVID-19 Some cases of may be related to persistent autoinhibition. If so, these patients may respond to the same immune-targeted therapies that have been successful in MIS-C where autoantibody production is now documented.
Finally, by testing patients immediately after COVID-19 recovery, we can establish a baseline and begin tracking the possible emergence of new cases of autoimmunity after this terrible disease, and early rheumatological intervention if necessary. Can plan
Now we have the equipment. The time has come to start using them.
Matthew Woodruff, Instructor, Lonce Center for Human Immunology, Emory University.
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