Improving the Outcomes of Immunocompromised Patients with COVID-19

Haidar, Ghady; Mellors, John W

Recent case studies have highlighted that certain immunocompromised individuals are at risk for prolonged SARS-CoV-2 replication, intra-host viral evolution of multiply-mutated variants, and poor clinical outcomes. The immunologic determinants of this risk, the duration of infectiousness, and optimal treatment and prevention strategies in immunocompromised hosts are ill-defined. Of additional concern is the widespread use of immunosuppressive medications (corticosteroids, IL-6 antagonists) to treat COVID-19, which may enhance and prolong viral replication in the context of immunodeficiency. We outline the rationale for four inter-related approaches to usher in an era of evidence-based medicine for optimal management of immunocompromised patients with COVID-19: 1) multicenter pathogenesis and outcomes studies to relate the risk of severe disease to the type and degree of immunodeficiency; 2) studies evaluating immunologic responses to SARS-CoV-2 vaccines; 3) studies evaluating the efficacy of monoclonal antibodies for primary prophylaxis; and 4) clinical trials of novel antiviral agents for the treatment of COVID-19.