1 Introduction
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel strain of human coronavirus that surfaced in 2019, which caused a global pandemic of Coronavirus Infectious Disease 2019 (COVID-19)1. COVID-19 has great heterogeneity in symptoms, severity, and prognosis, ranging from no symptoms to death2. The mortality among critically ill COVID-19 patients has been reported to be 61.5%3. Therefore, it is necessary and urgent to explore the related risk and protective factors of severe COVID-19.
Allergic diseases (including allergic rhinitis (AR), eczema/dermatitis, asthma, etc.) were generally considered protective against COVID-19. Analysis of the large prospective cohorts of UK Biobank (UKB) shows that AR was concerned with a lower rate of SARS-CoV-2 infection, but not the severity, while asthma was protective against infection only in people under 65 years4. Patients with allergic asthma were reported to have a lower risk of death after SARS-CoV-2 infection than patients with nonallergic asthma in real-world cohorts5. However, previous studies are mainly observational studies with possible reverse causality, and the confounding factors cannot be completely removed. Whether the link between allergic diseases and COVID-19 is causal is not yet fully established.
Mendelian randomization (MR) studies use genetic data as a bridge to exploring the causal association between exposure phenotypes and outcomes. Since single nucleotide polymorphisms (SNPs) are used as instrumental variables in MR analysis, the effect of confounding factors will be smaller. Moreover, exposure phenotypes cannot influence SNPs in reserve, so MR analysis is not subject to reverse causality. Importantly, in contrast to traditional epidemiologic methods, the MR study can suggest the directionality of exposure and outcome, and thus a causal relationship rather than an association6. A relatively comprehensive MR study showed that physical activity, high education level, never smoking, and asthma were protective factors against hospitalized COVID-197. It was also suggested through MR analysis that asthma was a protective factor for SARS-CoV-2 infection8. To date, no study has comprehensively explored the causal relationship between allergic diseases and COVID-19. Herein, We conducted a bidirectional, two-sample MR analysis for the allergic disease and two COVID-19 outcomes (SARS-CoV-2 infection and severe COVID-19), and then univariate and multivariate MR analyses for the relationships between various allergic diseases (including different subtypes of asthma) and severe COVID-19. This study may shed more light on the pathophysiology of COVID-19 and has potential clinical and public health implications.