Dr. Utz explained that, although this study had just a small sample of patients, these findings provide some general trends that may indicate the relative frequencies with which different autoantibodies are seen in patients with COVID-19.
Anti-cytokine autoantibodies: Steven Holland, MD, director of the Division of Intramural Research and chief of the Immunopathogenesis Section at the National Institutes of Health, and colleagues have described an adult-onset immunodeficiency with susceptibility to mycobacterial infections due to the presence of anti-interferon (IFN) gamma autoantibodies.4 This finding implies that some apparently infectious diseases are the consequence of autoimmunity in the form of anti-cytokine antibodies. In almost 1,000 patients with life-threatening COVID-19, more than 100 had autoantibodies against type-1 IFNs, but such antibodies were either completely or nearly absent in patients with asymptomatic SARS-CoV-2 infection, mild infection or healthy controls.5 It’s unclear if COVID-19 unmasks anti-cytokine autoantibodies, but these autoantibodies seem to significantly effect the function of the adaptive and innate immune systems.
Given the role chemokines play in orchestrating immune cell trafficking, it’s possible that antibodies against these chemokines may play beneficial roles in reducing the immune-mediated sequelae of viral infection.
Chemokines: Being somewhat provocative, Dr. Utz said that when he was in medical training, the conventional wisdom was that autoantibodies were essentially always harmful or bad. However, Muri et al. found that antibodies against specific chemokines widely present in patients after COVID-19 infection were associated with favorable disease outcomes and were protective against the development of long COVID for up to one year after infection.6 Thus, given the role chemokines play in orchestrating immune cell trafficking, it’s possible antibodies against these chemokines may play beneficial roles in reducing the immune-mediated sequelae of viral infection.
Dr. Utz himself contributed to research examining the prevalence of autoantibodies in non-SARS-CoV-2 respiratory infections and critical illness. By profiling IgG autoantibodies in more than 260 patients with viral, bacterial and non-infectious critical illnesses, the researchers found anti-cytokine antibodies were present in more than half of these patients, were more common in infected vs. noninfected patients and often showed receptor-blocking activity against surface receptors for type I IFN, GM-CSF and interleukin 6. Additionally, autoantibodies directed against connective tissue disease-associated autoantigens were observed.7
The researchers note that we do not yet fully understand the mechanisms by which tolerance to self-antigens is broken—perhaps transiently—in COVID-19, influenza and other infections. Further research on this topic may shed light on how the infectious process results in the promulgation of autoantibodies.
