COVID-19 Can Make Patients' Immune Systems Attack Their Own Bodies, Study Shows

 Across the globe, immunologists who retooled their labs to hitch the fight against SARS-CoV-2 are furiously trying to clarify why some people get so sick while others recover unscathed. The pace is dizzying, but some clear trends have emerged.

One area of focus has been the assembly of antibodies – powerful proteins capable of disabling and killing invading pathogens like viruses. Of great concern has been the sporadic identification of so-called autoreactive antibodies that, rather than targeting disease-causing microbes, target the tissues of people full of severe cases of COVID-19.

Early studies implicated these autoantibodies in dangerous blood clots forming in patients admitted to medical aid. More recently, they need been linked to severe disease by inactivating critical components of viral immune defenses during a significant fraction of patients with severe disease.

As an immunologist within the Lowance Center for Human Immunology at Emory University, I've got been investigating the response accountable for producing antibodies in COVID-19. Under the direction of Dr. Ignacio Sanz, our group has previously investigated immune responses contributing to autoantibody production in autoimmune disorders like lupus, and more recently in severe cases in COVID-19.

However, while we were ready to characterize the response in COVID-19 patients as autoimmune like, we couldn't confirm the assembly of autoantibodies hidden within their antiviral responses.

Now we can.

In a newly released study awaiting peer-review, we describe the alarming finding that within the sickest patients with COVID-19, autoantibody production is common – a finding with a large potential impact on both acute patient care and infection recovery.

Severe infection is linked with autoantibody production

Autoantibodies are available "flavors" that are usually related to specific disease types. Patients with lupus, for instance, will often have antibodies that concentrate on their own DNA – the molecules that compose the human genome.

Patients with autoimmune disease arthritis are less likely to own those antibodies, but more likely to indicate positive tests for autoantibody – antibodies that focus on other antibodies.

In this study, the Lowance Center group analyzed the medical charts of 52 patients in medical aid 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 very style of disorders.

The results are stark. quite 1/2 the 52 patients tested positive for autoantibodies. In patients with the very best levels of C-reactive protein (a marker of inflammation) within the blood, over two-thirds displayed evidence that their system was producing antibodies attacking their own tissue.

While these findings raise concerns, there are things that our data don't reveal. Although patients with severe disease clearly display autoantibody responses, the information doesn't tell us to what extent these autoantibodies contribute to the foremost severe symptoms of COVID-19.

It may be that severe viral illness routinely ends up in the assembly of autoantibodies with little consequence; this might just be the primary time we're seeing it. We also do not know how long the autoantibodies last. Our data suggest that they're relatively stable over some weeks. But, we want follow-up studies to know if they're persisting routinely beyond infection recovery.

Importantly, we believe that the autoreactive responses we've got identified here are specific to the SARS-CoV-2 infection – there's no reason to believe that similar results would be expected through vaccination against the virus.

Understanding the role of autoantibodies in COVID-19

However, while it's possible that these autoantibodies are benign, or maybe helpful in an exceedingly yet-unidentified manner, it is also possible that they are not. Maybe these self-targeted antibody responses do indeed contribute to disease severity, helping explain the delayed onset of severe symptoms in some patients which will correlate with antibody production.

This could be a reason that treatment with dexamethasone, an immunosuppressant often accustomed quell "flare-ups" of autoimmune disorders, could be effective in treating patients with only the foremost severe disease. it's also possible that these responses aren't short-lived, outlasting the infection and contributing to ongoing symptoms now experienced by a growing number of "long-hauler" COVID-19 patients.

Most concerning, it's possible that these responses could self-perpetuate in some patients, leading to the emergence of recent, permanent autoimmune disorders.

My colleagues and that I sincerely hope that this is often not the case – rather, that the emergence of autoantibodies in these patients could be a red herring, a quirk of viral response in some patients that may resolve on its own.

But we'd like to try to better than hope – we want to ask the correct questions and determine the answers. Fortunately, this study also gives us the tools to try and do that.

Autoreactive antibody test may reveal better treatments

The tests that were run on these patients to work out their "autoreactive profile" don't seem to be specialized. they're available to most hospital labs across the country.

Indeed, the 2 most typical antibodies that we discover in these patients, antinuclear antibodies and autoantibody, are detected by common tests utilized by rheumatologists.

Our study shows that by testing for just these two autoantibodies, and also the inflammatory marker CRP, we could also be ready to identify patients more likely to be experiencing potentially dangerous immune responses which may take pleasure in more aggressive immune modulation.

Further, autoreactivity testing might help identify patients who might enjoy rheumatological follow-up to observe recovery and help us understand whether some cases of "long-hauler" COVID-19 could be associated with persisting autoantibodies. If so, these patients might reply to the identical immune-targeted therapies that are successful in MIS-C where autoantibody production has now been documented.

Finally, by testing patients immediately following COVID-19 recovery, we will establish baselines and start to trace the possible emergence of the latest cases of autoimmunity following this terrible disease, and plan early rheumatological intervention if needed.

We now have the tools. it is time to begin using them. The Conversation

Matthew Woodruff, Instructor, Lowance Center for Human Immunology, Emory University.