Data support COVID-19 as autoimmunity trigger in patients without preexisting IMIDs
Click Here to Manage Email Alerts
Emerging data are beginning to show that COVID-19 can induce autoimmunity in patients without preexisting immune-mediated inflammatory diseases, with consequences that are yet unknown, according to a speaker at the 2021 Interdisciplinary Autoimmune Summit.
“This raises several questions. Will this be able to flare IMIDs? Will this be able to cause new autoimmune diseases? Will it contribute to the long-COVID syndrome?” Leonard H. Calabrese, DO, professor of medicine at the Cleveland Clinic Lerner College of Medicine and RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, told attendees at the virtual meeting.
“There is no doubt that viruses can induce autoimmunity,” he added. “We have already seen patients with this infection, since there are 40 million people on the planet that have had this — probably 50 million by now. We see Guillain-Barré and immune cytopenias, but we are still learning a lot.”
Calabrese highlighted four recent studies, three of which have yet to be published but are available on the medRxiv.org archive, that he said demonstrate “significant autoantibodies” in patients who develop COVID-19. In one study, Nahid Bhadelia, MD, MA, of the Boston University School of Medicine, and colleagues reported data that support induction of immune responses to self-epitopes during acute, severe COVID-19, with evidence of general B-cell hyperactivation.
In another, Eric Y. Wang, of the Yale School of Medicine, and colleagues concluded that their findings demonstrate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.
In the third study still pending peer review, Sarah Esther Chang, of the Stanford University School of Medicine, and colleagues stated that SARS-CoV-2 triggers the development of new-onset IgG autoantibodies in a significant proportion of patients hospitalized with COVID-19, which are positively correlated with immune responses to SARS-CoV-2 proteins.
The lone published study of the group appeared online in January in Nature. In it, Alexis J. Combes, PhD, of the University of California, San Francisco, and colleagues show potential targets for immunotherapies in patients with severe COVID-19 to re-engage viral defense.
“Most of these are not peer-reviewed ... but these are four high-impact papers from just the past few weeks, all of which, finally, in agreement, identified that patients with COVID-19 elaborate autoantibodies,” Calabrese said. “And this isn’t just trivial [antinuclear antibodies] here and there — significant autoantibodies.”
The most impactful of these studies, according to Calabrese, comes from Chang and colleagues. That study, led by senior author Paul J. Utz, MD, of the Stanford University School of Medicine, included 147 patients from several centers — including Stanford and the University of Pennsylvania — all of whom were hospitalized with COVID-19.
According to the findings, the researchers identified autoantibodies approximately 50% of participants.
“They used a very robust platform to screen for autoantibodies, and the bottom line was that they found autoantibodies in half of these patients,” Calabrese said. “Some were transient, but most were persistent, even well into recovery. And the final observation was that they appeared to track with antiviral antibodies.”
According to Calabrese, the long-term effects of this, and of post-COVID-19 sequelae in general, are still unknown. Data published in Morbidity and Mortality Weekly Report and JAMA indicate that 35% of patients with COVID-19 fail to return to their usual state of health at 2-3 weeks, including 20% of those without previous chronic conditions. In addition, 55% showing three or more persistent symptoms 60 days after symptom onset.
Meanwhile, out of 4,182 cases of patients who defined themselves as “normal” prior to COVID-19, symptoms were reported by 13.3% after 4 weeks, by 4.5% after 8 weeks, and by 2.3% after 12 weeks.
“Basically, depending upon how you define it, this is a big problem,” Calabrese said. “A third. A quarter. Half. If we have tens of millions of people in this country that have had COVID-19, this means that there are millions of people who have something that is syndromically there.”
He added, “I think there is just so much going on here, and we are just putting our foot the river. I’ll just leave you with this thought: we are closer to the beginning than the end of this.”
Collapse
Calabrese LH. Advances in Understanding of the Immunobiology of COVID-19 — Implications for Autoimmune and Autoinflammatory Diseases. Presented at: Interdisciplinary Autoimmune Summit. April 15-18, 2021 (virtual meeting).
Click Here to Manage Email Alerts