2 Methods
2.1 Study design
A full description of the study design was displayed in Figure 1. A bidirectional, two-sample MR analysis was first conducted to investigate causal associations between the allergic disease, including asthma and/or hay fever (or AR) and/or eczema (or atopic dermatitis(AD)), and the two COVID-19 outcomes (SARS-CoV-2 infection and severe COVID-19). Univariate MR analysis (i.e. two-sample MR analysis) was then designed to explore the causal associations between various allergic diseases (hay fever, AR, or eczema/AR/AD/asthma) and severe COVID-19. Multivariate MR analysis was utilized to assess the independent influence of these allergic diseases on the risk of severe COVID-19. Finally, univariate and multivariate MR analyses were used to explore the causal relationship between various subtypes of asthma and severe COVID-19.
The MR analysis was on the strength of three assumptions: ①The SNPs utilized as instrumental variables (IVs) have connections with the exposure; ②The IVs have nothing to do with any confounders; ③IVs are not directly related to outcome, and they influence the outcome only through the exposure, not through any alternative pathways9.