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.