Introduction: Asthma control and severity are important when assessing the risk of severe outcomes of COVID-19. The aim of this study was to explore synergy effects of multiple manifestations of uncontrolled asthma associated with severe COVID-19.

Methods: In 2014-2020, adult patients with uncontrolled asthma, defined as Asthma Control Test (ACT) score ?19, were identified in the Swedish National Airway Register (SNAR) (n=24533). The SNAR database was linked with national registers to obtain information on severe COVID-19, defined as hospitalization and/or death due to COVID-19 (n=221). The synergy effect of multiple manifestations of uncontrolled asthma was studied as one to three of: 1) ACT ?15 (very poorly controlled asthma); 2) prior exacerbations (?2 dispensed oral corticosteroids); and 3) asthma inpatient/secondary care, during the year before the pandemic. Poisson regression analyses were conducted with severe COVID-19 as the dependent variable.

Results: Among patients with uncontrolled asthma (ACT?19) with vs. without severe COVID-19: 45.7 vs. 42.3% had one manifestation of uncontrolled asthma, 18.1 vs. 9.1% had two, and 5.0 vs. 2.1% had three (all p<0.001). The risk ratio (RR) of severe COVID-19 increased with an increasing number of manifestations of uncontrolled asthma: one, RR 1.49 (95% CI 1.09-2.02), two, RR 2.42 (95% CI 1.64-3.57) and three, RR 2.96 (95% CI 1.57- 5.60), when adjusted for sex, age, and BMI.

Conclusions: The synergy effect of multiple manifestations of uncontrolled asthma can increase the risk of severe COVID-19 up to three times. This should be taken into account when monitoring patients with uncontrolled asthma and COVID-19.