Allergic diseases were recently reported related to both SARS-CoV-2
infection and severe COVID-19 through observational studies. However,
their causal relationship remains unclear. Herein, we performed
univariate and multivariate Mendelian randomization (MR) studies to
investigate the causal association between various allergic diseases and
COVID-19. Genome-wide association studies (GWAS) summaries were used in
this study, with 360838 participants in the allergic disease database,
455449 in asthma, 217914 in allergic rhinitis (AR), and 205764 in atopic
dermatitis (AD). In univariate MR analysis, the allergic disease was not
causally in connection with SARS‐CoV‐2 infection but have a causal
protective effect on severe COVID-19. In contrast, no significant causal
effect was found of SARS-CoV-2 infection/severe COVID-19 on the allergic
disease. AD, mixed asthma, and childhood asthma were causal protective
factors for severe COVID-19. Multivariate MR analysis further revealed
the dominant role of asthma in allergic diseases and the dominance of
childhood asthma in asthma subtypes. In summary, this study, based on
the population genetic variation model, pointed out the protective
effect of allergic diseases against severe COVID-19, which may provide
some inspiration for further exploration of the pathophysiological
mechanisms of COVID-19.