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

<b>Rationale:</b> Epidemiologic studies on patients with asthma and <i>in vitro</i> data suggest a protective role of type 2 (T2) inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. <b>Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.