Causal associations between chronic hepatitis B and COVID-19 in East Asian populations

Abstract

Background: The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies. Methods: We explored the total causal and direct causal associations between CHB and the three COVID-19 outcomes using univariate and multivariate Mendelian randomization (MR) analyses, respectively. Genome-wide association study datasets for CHB and COVID-19 were obtained from the Japan Biobank and the COVID-19 Host Genetics Initiative, respectively. Results: Univariate MR analysis showed that CHB increased the risk of SARS-CoV-2 infection (OR = 1.04, 95% CI 1.01–1.07, P = 3.39E−03), hospitalized COVID-19 (OR = 1.10, 95% CI 1.06–1.13, P = 7.31E−08), and severe COVID-19 (OR = 1.16, 95%CI 1.08–1.26, P = 1.43E−04). A series of subsequent sensitivity analyses ensured the stability and reliability of these results. In multivariable MR analyses adjusting for type 2 diabetes, body mass index, basophil count, and smoking, genetically related CHB is still positively associated with increased risk of SARS-CoV-2 infection (OR = 1.06, 95% CI 1.02–1.11, P = 1.44E−03) and hospitalized COVID-19 (OR = 1.12, 95% CI 1.07–1.16, P = 5.13E−07). However, the causal link between CHB and severe COVID-19 was attenuated after adjustment for the above variables. In addition, the MR analysis did not support the causal effect of COVID-19 on CHB. Conclusions: This study provides evidence that CHB increases COVID-19 susceptibility and severity among individuals of East Asian ancestry.