Asthma Phenotypes and COVID-19 Risk: A Population-based Observational Study

Abstract

Rationale: Studies have suggested some patients with asthma are at risk of severe coronavirus disease (COVID-19), but they have had limited data on asthma phenotype and have not considered if risks are specific to COVID-19. Objectives: To determine the effect of asthma phenotype on three levels of COVID-19 outcomes. Compare hospitalization rates with influenza and pneumonia. Methods: Electronic medical records were used to identify patients with asthma and match them to the general population. Patient-level data were linked to Public Health England severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test data, hospital, and mortality data. Asthma was phenotyped by medication, exacerbation history, and type 2 inflammation. The risk of each outcome, adjusted for major risk factors, was measured using Cox regression. Measurements and Main Results: A total of 434,348 patients with asthma and 748,327 matched patients were included. All patients with asthma had a significantly increased risk of a General Practice diagnosis of COVID-19. Asthma with regular inhaled corticosteroid (ICS) use (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01-1.61), intermittent ICS plus add-on asthma medication use (HR, 2.00; 95% CI, 1.43-2.79), regular ICS plus add-on use (HR, 1.63; 95% CI, 1.37-1.94), or with frequent exacerbations (HR, 1.82; 95% CI, 1.34-2.47) was significantly associated with hospitalization. These phenotypes were significantly associated with influenza and pneumonia hospitalizations. Only patients with regular ICS plus add-on asthma therapy (HR, 1.70; 95% CI, 1.27-2.26) or frequent exacerbations (HR, 1.66; 95% CI, 1.03-2.68) had a significantly higher risk of ICU admission or death. Atopy and blood eosinophil count were not associated with severe COVID-19 outcomes. Conclusions: More severe asthma was associated with more severe COVID-19 outcomes, but type 2 inflammation was not. The risk of COVID-19 hospitalization appeared to be similar to the risk with influenza or pneumonia.

Keywords: COVID-19; allergic rhinitis; asthma; disease severity; influenza.

Figure 1.

Flow diagram of inclusion and exclusion criteria. COPD = chronic obstructive pulmonary disease; CPRD = Clinical Practice Research Datalink; GP = General Practice; HES = Hospital Episode Statistics; NCS = nasal corticosteroid; ONS = Office of National Statistics; PHE = Public Health England.

Figure 2.

Comparing forest plots of the associations between asthma phenotype and each coronavirus disease (COVID-19) outcome, after adjusting for all other risk factors (see Figure E7 for forest plot including all variables and Tables E3, E5, and E6 for unadjusted and adjusted effect estimates). GP = General Practice; ICS = inhaled corticosteroid; SABA = short-acting β-agonist.

Figure 3.

Comparing forest plots of the associations between asthma phenotype and hospitalization for the three different respiratory infections—COVID-19, influenza, and pneumonia—after adjusting for all other risk factors (ethnicity, socioeconomic deprivation, obesity, atopy, cardiac disease, diabetes, cerebrovascular accident, chronic renal failure, dementia, and cancer). COVID-19 = coronavirus disease; GP = General Practice; ICS = inhaled corticosteroid; SABA = short-acting β-agonist.

Figure 4.

Association between maximum absolute blood eosinophil count and ICU admission or death in the patients with asthma. The model was adjusted for sex, age, ethnicity, socioeconomic deprivation, obesity, atopy, cardiac disease, diabetes, cerebrovascular accident, chronic renal failure, dementia, and cancer. The solid black line represents the adjusted hazard ratio for the outcome (ICU admission or death) for the continuous variable of maximum absolute blood eosinophil count. The dashed black lines represent the 95% confidence interval of the hazard ratio.