Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19

BACKGROUND: Glomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients. SUMMARY: The advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However, patients on ISTs were excluded from initial vaccine clinical trials. Thus, only limited and incomplete data are available currently regarding the potential impact of immunosuppression on immune response to or efficacy of the SARS-CoV-2 vaccines. However, new insights are emerging from SARS-CoV-2 vaccine studies, and impacts of ISTs on conventional vaccines are useful to consider. Mechanisms of immunosuppressive agents commonly used in the treatment of GD are reviewed with respect to implications for immune responses induced by SARS-CoV-2 vaccines. ISTs discussed include corticosteroids; alkylating agents; antimetabolites; calcineurin or mammalian target of rapamycin inhibitors; CD38+, CD20+, or CD19+ cell depletion; and complement protein C5 inhibition. KEY MESSAGES: Many immunosuppressive therapies may potentially attenuate or impair protective immunity of the SARS-CoV-2 vaccines. However, as vaccines currently in use employ mRNA or nonreplicative viral vectors, they appear to be safe in patients on immunosuppression, further favoring vaccination. Moreover, predominant SARS-CoV-2 vaccines are likely to afford at least partial protective immunity through one or more immune mechanisms even in patients on IST. Guidelines and emerging strategies are also considered to optimize vaccine protection from COVID-19.