最近的研究表明,哮喘可能对COVID-19有保护作用。我们旨在调查哮喘与两种COVID-19结局之间的因果关系,并探索强调这种联系的机制。
GWAS的汇总结果用于分析,包括哮喘(88,486例和447,859例对照),COVID-19住院(6,406例COVID-19住院病例和902,088例对照),和COVID-19感染(14,134例COVID-19病例和1,284,876例对照)。进行了孟德尔随机化(MR)分析,以评估哮喘对两种COVID-19结局的因果影响。进行了跨性状荟萃分析,以分析COVID-19住院和哮喘共有的两个基因座内的遗传变异。
哮喘与COVID-19住院风险降低(比值比(OR):0.70,95%置信区间(CI):0.70-0.99)和COVID-19感染风险降低(OR:0.83,95CI:0.51-0.95)。哮喘和COVID-19共有两个全基因组重要基因,包括9q34.2地区的ABO和12q24.13地区的OAS2。荟萃分析显示,ABO和ATXN2含有对COVID-19和哮喘均具有多效性作用的变体。
总之,我们的结果表明,哮喘的遗传倾向与SARS-CoV-2和严重COVID-19疾病的易感性降低有关,这可能是由于持续炎症的保护作用,可能,早期对COVID-19的相关补偿反应。
Recent studies suggest that asthma may have a protective effect on COVID-19.We aimed to investigate the causality between asthma and two COVID-19 outcomes and explore the mechanisms underlining this connection.
Summary results of GWAS were used for the analyses, including asthma (88,486 cases and 447,859 controls), COVID-19 hospitalization (6,406 hospitalized COVID-19 cases and 902,088 controls), and COVID-19 infection (14,134 COVID-19 cases and 1,284,876 controls). The Mendelian randomization (MR) analysis was performed to evaluate the causal effects of asthma on the two COVID-19 outcomes. A cross-trait meta-analysis was conducted to analyze genetic variants within two loci shared by COVID-19 hospitalization and asthma.
Asthma is associated with decreased risk both for COVID-19 hospitalization (odds ratio (OR): 0.70, 95% confidence interval (CI): 0.70-0.99) and for COVID-19 infection (OR: 0.83, 95%CI: 0.51-0.95). Asthma and COVID-19 share two genome-wide significant genes, including
ABO at the 9q34.2 region and OAS2 at the 12q24.13 region. The meta-analysis revealed that
ABO and ATXN2 contain variants with pleiotropic effects on both COVID-19 and asthma.
In conclusion, our results suggest that genetic liability to asthma is associated with decreased susceptibility to SARS-CoV-2 and to severe COVID-19 disease, which may be due to the protective effects of ongoing inflammation and, possibly, related compensatory responses against COVID-19 in its early stage.