COVID-19 causes some patients’ immune systems to attack their own bodies,...

Around the world, immunologists who have upgraded their laboratories to join the battle against SARS-CoV-2 are furiously trying to explain why some people get so sick while others recover unharmed. The pace is dizzying, but some clear trends can be seen.

One focus was the production of antibodies – powerful proteins that can deactivate and kill invading pathogens such as viruses. Of great importance was the sporadic identification of so-called autoreactive antibodies that do not target disease-causing microbes, but rather the tissue of people suffering from severe cases of COVID-19.

Early studies implicated these autoantibodies in dangerous blood clots that form in patients admitted to the intensive care unit. More recently, they have been linked to serious illness by inactivating critical components of the viral immune system in a significant proportion of patients with serious illnesses.

As an immunologist at Emory University’s Lowance Center for Human Immunology, I studied the immune response responsible for producing antibodies in COVID-19. Under the direction of Dr. Ignacio Sanz previously studied immune responses that contribute to autoantibody production in autoimmune diseases such as lupus and, more recently, in severe cases of COVID-19 in our group. Although we were able to characterize the response in COVID-19 patients as autoimmune, we could not confirm the production of autoantibodies hidden in their antiviral responses.

Now we can.

In a newly published study awaiting peer review, we describe the alarming finding that autoantibody production is common in sick patients with COVID-19 – a finding with great potential implications for acute patient care and recovery from infection.

Severe infection is associated with autoantibody production

Autoantibodies come in “flavors” that are normally associated with certain types of diseases. For example, patients with lupus often have antibodies that target their own DNA – the molecules that make up the human genome.

People with the autoimmune disease rheumatoid arthritis are less likely to have these antibodies, but are more likely to test positive for rheumatoid factor – antibodies that target other antibodies.

In this study, the Lowance Center group analyzed the medical charts of 52 ICU patients diagnosed with COVID-19. None of them had a history of autoimmune disease. However, they were tested for autoantibodies, which have been found in a variety of diseases, during infection.

The results are strong. 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 tissues.

While these results raise concerns, there are things that our data does not reveal. Although patients with severe illness clearly show autoantibody responses, the data does not say how much these autoantibodies contribute to the most severe symptoms of COVID-19.

It could be that serious viral disease routinely leads to the production of autoantibodies with little consequence; This could be the first time we see it. We also don’t know how long the autoantibodies last. Our data suggest that they are relatively stable over a few weeks. However, we need follow-up studies to understand whether they routinely persist beyond infection recovery.

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.

Understanding the role of autoantibodies in COVID-19

While it is possible that these autoantibodies are benign or even helpful in ways that have not yet been identified, it is also possible that they are not. Perhaps these self-directed antibody responses actually contribute to the severity of the disease and explain the delayed onset of severe symptoms in some patients that may be correlated with antibody production.

This could be a reason why treatment with dexamethasone, an immunosuppressant often used to suppress the flare-ups of autoimmune diseases, may be effective in treating patients with just the most serious illness. It is also possible that these reactions are short-lived, survive the infection, and contribute to the lingering symptoms that are now occurring in a growing number of long-distance COVID-19 patients.

Most worrisome, in some patients, these reactions can continue on their own, leading to the development of new, permanent autoimmune diseases.

My colleagues and I sincerely hope that this is not the case – rather that the occurrence of autoantibodies in these patients is a red herring, a characteristic of a viral immune response in some patients that resolves on its own. But we have to do better than hope – we have to ask the right questions and find out the answers. Fortunately, this study also gives us the tools to do that.

The autoreactive antibody test can yield better treatments

The tests that were performed on these patients to determine their “autoreactive profile” are not specialized. They are available to most hospital laboratories across the country. In fact, the two most common antibodies we find in these patients, antinuclear antibodies and rheumatoid factor, are detected by joint tests by rheumatologists.

Our study shows that by testing for just these two autoantibodies and the inflammatory marker C-reactive protein, we may be able to identify patients who are more likely to have potentially dangerous immune responses who could benefit from more aggressive immune modulation.

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In addition, autoreactivity tests can help identify patients who might benefit from a rheumatic follow-up visit to monitor recovery and help us understand whether some cases of long-range COVID-19 function might be related to persistent autoantibodies. In this case, these patients may respond to the same immunospecific therapies that were successful with MIS-C, where autoantibody production has now been documented.

Finally, by testing patients as soon as they recover from COVID-19, we can establish baseline levels and begin tracking the possible emergence of new cases of autoimmunity after this terrible disease and planning early rheumatological intervention if necessary.

We now have the tools. It is time to use it.