Asthma and COVID-19: Unveiling Outcome Disparities and Treatment Impact Based on Distinct Endotypes

Rationale: Epidemiologic studies on patients with asthma and in vitro data suggest a protective role of type 2 (T2) inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: Using a large, multisite cohort, we studied clinical outcomes after SARS-CoV-2 infection in multiple asthma endotypes and examined the effects of T2-directed biologics in infected patients with asthma. Methods: The National COVID Cohort Collaborative Data Enclave was used to identify and stratify patients with asthma by endotype to include those with non-T2 and T2 asthma, as well as exposure to T2-directed biologic therapy. We evaluated the risk of hospitalization, invasive mechanical ventilation, and 90-day mortality by endotype and exposure to biologics. Results: For this study, 402,376 patients met the inclusion criteria, of whom 138,142 (34%) were characterized as having non-T2 asthma and 264,234 (66%) as having T2 asthma, a group further divided into 104,823 (26%) atopic, 84,440 (21%) eosinophilic, and 74,971 (19%) T2-high asthmatic endotypes. Compared with patients with non-T2 asthma, those with atopic and T2-high asthma experienced decreased odds of hospitalization and 90-day mortality. Conversely, patients with eosinophilic asthma experienced higher odds of hospitalization, intubation, and 90-day mortality. Exposure to T2-directed biologic therapies did not alter outcomes after propensity score matching. In contrast, maximum eosinophil count and recent systemic corticosteroid use were directly correlated with increased odds of all outcomes. Conclusions: Coronavirus disease (COVID-19) outcomes differ depending on asthma endotype, with patients with atopic asthma experiencing lower odds and those with eosinophilic asthma experiencing higher odds of deleterious outcomes. T2-directed biologic treatment did not alter these outcomes, but recent systemic corticosteroid use predisposes all patients with asthma to adverse outcomes.