![]() Furthermore, the direct effect of genetically related CHB on three COVID-19 outcomes was investigated using multivariate MR (MVMR) analysis. The instrumental variable used in this MR analysis needs to meet three important conditions: (1) the SNPs must be strongly associated with exposure (2) the SNPs are independent of potential confounders (3) the genetic variant(s) only influence the outcome through risk factors. This analysis method effectively emulates a randomized controlled trial by randomly assigning single nucleotide polymorphisms (SNPs) to offspring. We first assessed the causal associations between CHB and the three COVID-19 outcomes by univariate MR analysis. ![]() The causal effect of COVID-19 on CHB was also assessed. To investigate potential causal links between genetic susceptibility to CHB and three COVID-19 outcomes, namely SARS-CoV-2 infection, hospitalized COVID-19, and severe COVID-19, we conducted MR analyses using available genome-wide association study (GWAS) datasets. However, there are no studies on the MR analysis between CHB and COVID-19 to date. This method is not susceptible to confounding factors and is not prone to reverse causality because genetic variants are randomly allocated before birth. Mendelian randomization (MR) analysis uses genetic variants as instrumental variables to assess potential causal links between exposures and outcomes. The variability in these findings could be attributed to potential confounding factors, population heterogeneity, and relatively small sample sizes. According to several studies, SARS-CoV-2-positive CHB patients had a higher risk of severe illness and fatality. Remarkably, a retrospective study conducted in Hong Kong revealed that neither past nor current HBV infection increased the risk of adverse outcomes or hepatic injury in patients with SARS-CoV-2 infection. However, several clinical studies have suggested that the extent of liver injury in patients with SARS-CoV-2 infection is not significantly different, regardless of whether they are co-infected with HBV or not. Some clinical studies have reported that co-infection with HBV and SARS-CoV-2 may lead to elevated cytokine levels and transaminase levels. ![]() Until now, it is unclear whether CHB increases susceptibility or severity of COVID-19. Ĭhronic hepatitis B (CHB) caused by the Hepatitis B virus (HBV) has imposed a sustained economic burden worldwide, especially in low- and middle-income regions or countries. Previous studies have established various risk factors associated with hospitalization or severe COVID-19, including advanced age, smoking, basophil count, and specific comorbidities like high body mass index (BMI) and type 2 diabetes. Efforts to identify the underlying diseases or contributing factors for COVID-19, especially the severity, could facilitate the optimization of treatment and management strategies for COVID-19. Although the majority of cases are mild or asymptomatic, a subset of patients might progress to develop septic shock or acute respiratory distress syndrome, even experiencing mortality. The disease can manifest with a broad spectrum of symptoms and severity levels. The ongoing Coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, continues to pose a significant public health threat on a global scale. This study provides evidence that CHB increases COVID-19 susceptibility and severity among individuals of East Asian ancestry. In addition, the MR analysis did not support the causal effect of COVID-19 on CHB. However, the causal link between CHB and severe COVID-19 was attenuated after adjustment for the above variables. 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). ![]() A series of subsequent sensitivity analyses ensured the stability and reliability of these results. Genome-wide association study datasets for CHB and COVID-19 were obtained from the Japan Biobank and the COVID-19 Host Genetics Initiative, respectively. 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. The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies.
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