All over the world, immunologists who reorganized their laboratories to combat SARS-CoV-2 are frantically trying to explain why some people are so ill while others are unscathed. The pace is dizzying and chaotic, but there are some obvious trends.
One of the areas of focus is the production of antibodies-powerful proteins that can destroy and kill invading pathogens (such as viruses). What has attracted great attention is the identification of the so-called autoreactive antibodies that are circulated, not against the microorganisms that cause the disease, but against the tissues of individuals with severe cases of COVID-19.
Early research involved these autoantibodies in dangerous clot formation in patients receiving intensive care. Recently, they have been associated with severe illness by inactivating key components of viral immune defense in a considerable number of severe patients.
As an immunologist at the Center for Human Immunity at Emory University, I have been studying the immune response responsible for the production of antibodies in COVID-19. Under the guidance of Dr. Ignacio Sanz, our research team has previously studied immune responses, which are caused in autoimmune diseases such as lupus and in severe cases in COVID-19 Autoantibody production. However, although we can characterize the response of COVID-19 patients as autoimmune-like, we cannot confirm the production of autoantibodies hidden in their antiviral response.
Now we can.
In the latest study awaiting peer review, we described a shocking finding that autoantibodies are common in the most sick COVID-19 patients-this finding is useful for acute patient care and infection recovery Both have great potential impact.
] Severe infections are related to the production of autoantibodies.
Autoantibodies have a "flavor" and are usually associated with specific disease types. For example, patients with lupus usually have antibodies against their own DNA-the molecules that make up the human genome.
Patients with rheumatoid arthritis with autoimmune diseases are less likely to have these antibodies, but are more likely to show a positive test for rheumatoid factor (antibodies against other antibodies).
In this study, the Lowance Center research team analyzed the medical records of 52 intensive care patients diagnosed with COVID-19. None of them had a history of autoimmune diseases. However, they have been tested for autoantibodies in various diseases during the course of infection.
The result is obvious. 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 of the evidence shows that their immune system is producing antibodies that attack their own tissues.
Although these findings have aroused people's attention, there are some things our data did not reveal. Although patients with severe diseases clearly show autoantibody reactions, the data does not tell us to what extent these autoantibodies have caused the most severe symptoms of COVID-19.
It may be that a serious viral disease usually leads to the production of autoantibodies with little consequence; this may be the first time we have seen it. We don't know how long autoantibodies can last. Our data shows that they are relatively stable within a few weeks. However, we need to conduct follow-up studies to understand whether they can persist after the infection returns.
Importantly, we believe that the self-reaction we identified here is against SARS-CoV-2 infection, so there is no reason to believe that similar results will be obtained by vaccination against this virus.
Understand its role. However, although these autoantibodies may be benign and may even help in unknown ways, it may not be the case.
Perhaps these self-targeted antibody responses do indeed contribute to the severity of the disease, and help explain the delayed onset of serious symptoms that may be related to antibody production in some patients.
This may be the reason why treatment with dexamethasone (an immunosuppressant commonly used to calm the "flaps" of autoimmune diseases) may only be effective for patients with the most severe disease. These reactions may not be short-lived, but persistent infections, and lead to the persistent symptoms that more and more "long-distance" COVID-19 patients now experience.
The most concerning is that these reactions may self-perpetuate in some patients, leading to the emergence of new permanent autoimmune diseases.
My colleagues and I sincerely hope that this is not the case-rather, the appearance of autoantibodies in these patients is a red herring, which is a quirk of the viral immune response of some patients, and it will resolve itself. But what we need to do is better than hoped-we need to ask the right questions and find the answers. Fortunately, this research also provides us with the tools to achieve this goal.
Auto-reactive antibody tests may reveal better treatments
The tests to determine "self-reactivity" for these patients are not specific. They can be used in most hospital laboratories across the country. In fact, the two most common antibodies we found in these patients, namely antinuclear antibodies and rheumatoid factor, were detected by routine testing methods used by rheumatologists.
Our research shows that only by testing these two autoantibodies and the inflammatory marker c-reactive protein, we can identify patients who are more likely to experience a potentially dangerous immune response, and these patients may be more aggressive Benefit from sexual immune regulation.
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In addition, automated reactivity testing may help identify patients who may benefit from follow-up rheumatism, to monitor recovery, and help us understand whether certain “long-distance travelers” COVID-19 cases are related to persistent self antibody. If so, these patients may respond to immune-targeted therapies that have been successful in MIS-C, which has now demonstrated the production of autoantibodies.
Finally, by testing patients immediately after recovery from COVID-19, we can establish a baseline and
We now have the tools to start tracking new autoimmune cases that may emerge after this terrible disease, and plan as soon as possible Carry out rheumatism intervention.
We now have these tools. Now it's time to start using them.
Matthew Woodruff, Lecturer, Lowance Center for Human Immunology, Emory University
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