Higher Prevalence of Immunosuppression Among US Adults: Implications for Coronavirus Disease 2019 and Respiratory Pathogen Vaccinations

Increasing use of immunosuppressive biologic therapies poses a challenge for infectious diseases. Immunosuppressed patients have a high risk for influenza complications and an impaired immune response to vaccines. The total burden of immunosuppressive conditions in the United States, including those receiving emerging biologic therapies, remains unknown. We used the national claims database MarketScan to estimate the prevalence of immunosuppressive conditions and risk for acute respiratory illnesses (ARIs). We studied 47.2 million unique enrollees, representing 115 million person-years of observation during 2012–2017, and identified immunosuppressive conditions in 6.2% adults 18–64 years of age and 2.6% of children <18 years of age. Among 542,105 ARI hospitalizations, 32% of patients had immunosuppressive conditions. The risk for ARI hospitalizations was higher among enrollees with immunosuppression than among nonimmunosuppressed enrollees. Future efforts should focus on developing improved strategies, including vaccines, for preventing influenza in immunosuppressed patients, who are an increasing population in the United States.

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups ( P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2–specific humoral responses, whereas only the S-HT group had reduced T cell–mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection. SARS-CoV-2 clearance differs by the extent of immunosuppression, with prolonged viral shedding occurring in those with severe immunosuppression. Interrogating Infection in Immunosuppression. Individuals who are immunosuppressed remain at increased risk of severe COVID-19, but this heterogenous patient pool should not be considered a monolith. Here, Li et al. asked whether the extent of immunosuppression a person has influences their ability to develop immunity and clear SARS-CoV-2 infections. The authors found that severe immunosuppression due to hematologic malignancy or transplant resulted in the longest time to viral clearance. These individuals also had evidence of increased intrahost viral evolution associated with resistance to antibody therapy and were marked by impaired humoral and T cell responses. Individuals with severe immunosuppression due to autoimmunity or B cell deficiency had, expectedly, impaired humoral responses but intact T cell responses, and those with nonsevere immunodeficiency had intact SARS-CoV-2–specific immunity mostly comparable to control participants. Together, these results highlight the importance of considering the type and severity of immunosuppression an individual is experiencing when considering their antiviral immunity. —Courtney Malo