Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy

Objectives Immunocompromised patients with immune mediated inflammatory diseases (IMIDs), undergoing therapy with B cell depleting agents are among the most vulnerable to experience severe COVID-19 disease as well as respond sub-optimally to SARS CoV-2 vaccines yet little is known about the frequency or severity of breakthrough infection in this population. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes. Methods Utilizing specific ICD codes the pharmacy records and COVID-19 registry at the Cleveland clinic were used to identify all patients with IMIDS treated with B cell depleting monoclonal antibodies who were vaccinated against SARs CoV-2 and experienced breakthrough infections. Each EMR record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, other therapies, details of B cell depleting therapy, and outcomes. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes. Results Of 1696 IMIDS patients on B cell depleting therapies 74 developed breakthrough COVID-19. Outcomes were severe with 24 (35%) hospitalized, 11 (15%) patients requiring critical care and 6 (8 %) deaths. Monoclonal antibodies were used on an outpatient basis to treat 21 with only a single patient requiring hospitalization without oxygen support and no deaths. Conclusions In IMIDS patients on B cell depleting therapies breakthrough infections are frequent and associated with severe outcomes. Outpatient use of monoclonal antibody therapy was associated with enhanced clinical outcomes.