Alveolar macrophages from people with severe eosinophilic asthma show differential antiviral responses to human rhinovirus 16 and SARS-CoV-2

ABSTRACT

Background: Rhinovirus is the most common trigger for exacerbations of asthma. Alveolar macrophages (AM) are a major site of RV infection and can also be infected by SARS-CoV-2. The pandemic caused by the SARS-CoV-2 raised concerns that patients with severe asthma (SA) would be at particularly high risk of developing severe disease. To date, evidence for poor outcomes in asthma remains limited suggesting a differential immune response to these two viruses. Method(s) Alveolar macrophages (AM) were isolated from bronchoalveolar lavage samples from patients with SA and infected with RV (n=13), SARS-CoV-2 alpha (B.1.1.7) (n=9) and delta (B.1.627.2)(n=8) variants. Antiviral mediators representing NF-KB-induced interferon-driven mRNAs (IL6 and IL8, RIGI and MDA5, respectively) were measured by qPCR, normalised to GAPDH and compared between infected AM and controls. Result(s) RV infected AM showed significant increases in mRNA expression of RIGI (4.39 fold change +/-4.68, p<0.001 vs control), MDA5 (2.96 fold change +/- 2.93, p=0.002 vs control) and IL6 (1.88 fold change +/- 0.98, p=0.006) compared to AM treated with control media alone, whilst IL8 did not significantly change. However, AM infected with SARS-CoV-2 alpha or delta variants showed no difference in levels of antiviral mediators compared to controls. Longitudinal analysis of AMs infected with SARS-CoV-2 alpha or delta variants showed no antiviral response. Conclusion(s) AM from subjects with severe asthma produce a pattern of anti-viral responses following RV infection that is absent when exposed to SARS-CoV-2 variants currently in circulation.