Background: Chronic respiratory disease is a well-characterised risk factor for increased hospitalisation and mortality in COVID-19 patients. There is conflicting evidence as to whether asthma patients are predisposed to SARS-CoV-2 infection or more severe disease outcomes. These clinical  studies are often confounded by asthma severity and inhaled corticosteroids for asthma management. 

Aims and objectives: To determine whether asthma patients are at increased risk of SARS-CoV-2 infection and greater inflammatory responses following infection. We hypothesise that asthma patients support increased viral replication and will be prone to infection-induced exacerbations. 

Methods: Primary broncho-epithelial cells (pBECs) were isolated from donors with moderate asthma (n=3) and healthy donors (n=4) and cultured at the air-liquid interface for 5 weeks. pBECs were then infected with SARS-CoV-2 (MOI 0.1) at the apical surface, after which apical washes were collected daily to measure viral titres and cytokines longitudinally. At 7 days post-infection (dpi), single cell RNA-sequencing (scRNAseq) was performed using the BD Rhapsody platform.

Results: We identified that asthma donors supported increased and prolonged SARS-CoV-2 viral replication as compared to healthy controls. These findings were further supported by scRNAseq at 7dpi. Importantly, we identified that asthma patients had markedly delayed Type I interferon production at baseline as compared to healthy control donors

Conclusions: Asthma patients are at increased risk of SARS-CoV-2 infection, likely due to abrogated Type I interferons at baseline which predisposes to asthma exacerbations.