The Many Facets of COVID-19: Experts Address Basic & Clinical Research Concepts in the COVID-19 Era

Dr. Sanz

On the subject of autoimmunity and COVID-19 infection, Iñaki Ignacio E. Sanz, MD, chief of the Division of Rheumatology and director of the Lowance Center for Human Immunology, Emory University, Atlanta, described how his team’s work on B cell responses in lupus may relate to important pathophysiologic mechanisms in COVID-19. Dr. Sanz and colleagues have previously described extrafollicular B cell responses that contribute to the generation of pathogenic autoreactive antibody-secreting cell (ASC) responses in SLE.⁷

Recently, Woodruff et al. showed that critically ill patients with COVID-19 also demonstrate extrafollicular B cell responses similar to those reported in autoimmune settings and that extrafollicular activation is strongly correlated with class-switched ASC expansions, high concentrations of SARS-CoV-2-neutralizing antibodies and poor clinical outcomes.⁸  

In a separate paper on relaxed peripheral tolerance in patients with COVID-19, Woodruff et al. identified B cell lineages with specificity both to SARS-CoV-2 and to autoantigens, including pathogenic autoantibodies against glomerular basement membrane. They described clinically relevant autoreactivity in these patients that correlated with severity of COVID-19 disease. The authors specifically identified anti-carbamylated protein responses as a common marker of broken peripheral tolerance in severe COVID-19.⁹

Dr. Son

MIS-C

Mary Beth Son, MD, section chief of the Rheumatology Program and director of services and outreach at Boston Children’s Hospital, focused on the topic of multi-system inflammatory syndrome in children (MIS-C).

Dr. Son reviewed the case definition for MIS-C published by the U.S. Centers for Disease Control and Prevention (CDC) and reviewed two important stipulations: 1) Patients may fulfill partial or full criteria for Kawasaki disease, but should still be reported as cases of MIS-C if they meet the case definition for this condition; and 2) MIS-C should be considered in any case of pediatric death with evidence of SARS-CoV-2 infection.¹⁰

In reviewing epidemiologic data from across the U.S. and the world, Dr. Son noted that a consistent three- to four-week delay exists between surges of COVID-19 cases and spikes in MIS-C cases, and many children with MIS-C may have had mild or asymptomatic infection. It’s clear that Black and Hispanic children are overrepresented among patients with MIS-C, which may be due, in part, to the higher incidence of severe COVID-19 in these patients, as well as the higher incidence of medical comorbidities, such as obesity, and social risk factors, such as poor access to healthcare.