Table1_Inflammation and immunity connect hypertension with adverse COVID-19 outcomes.DOCX

Objectives: To explore the connection of hypertension and severe COVID-19 outcomes.Methods: A total of 68 observational studies recording mortality and/or general severity of COVID-19 were pooled for meta-analyses of the relationship of severe COVID-19 outcomes with hypertension as well as systolic and diastolic blood pressure. Genome-wide cross-trait meta-analysis (GWCTM) was performed to explore the genes linking between hypertension and COVID-19 severity.Results: The results of meta-analysis with the random effect model indicated that pooled risk ratios of hypertension on mortality and severity of COVID-19 were 1.80 [95% confidence interval (CI) 1.54–2.1] and 1.78 (95% confidence interval 1.56–2.04), respectively, although the apparent heterogeneity of the included studies was detected. In subgroup analysis, cohorts of severe and mild patients of COVID-19 assessed in Europe had a significant pooled weighted mean difference of 6.61 mmHg (95% CI 3.66–9.55) with no heterogeneity found (p = 0.26). The genes in the shared signature of hypertension and the COVID-19 severity were mostly expressed in lungs. Analysis of molecular networks commonly affected both by hypertension and by severe COVID-19 highlighted CCR1/CCR5 and IL10RB signaling, as well as Th1 and Th2 activation pathways, and also a potential for a shared regulation with multiple sclerosis.Conclusion: Hypertension is significantly associated with the severe course of COVID-19. Genetic variants within inflammation- and immunity-related genes may affect their expression in lungs and confer liability to both elevated blood pressure and to severe COVID-19.

研究目标：探究高血压与重症COVID-19病患结局之间的关联。研究方法：共纳入68项观察性研究，记录了COVID-19的死亡率和/或一般严重程度，以进行meta分析，探究重症COVID-19病患结局与高血压以及收缩压和舒张压之间的关系。通过全基因组交叉性状meta分析（GWCTM）来探索连接高血压与COVID-19严重程度的基因。研究结果：采用随机效应模型进行的meta分析结果显示，高血压对COVID-19死亡率和严重程度的汇总风险比分别为1.80 [95%置信区间（CI）1.54–2.1]和1.78（95%置信区间1.56–2.04），尽管检测到纳入研究的显著异质性。在亚组分析中，欧洲评估的重症和轻症COVID-19队列的汇总加权平均差异为6.61 mmHg（95% CI 3.66–9.55），且未发现异质性（p = 0.26）。高血压与COVID-19严重程度共享特征中的基因主要在肺部表达。分析受高血压和重症COVID-19共同影响的多分子网络，突出了CCR1/CCR5和IL10RB信号通路，以及Th1和Th2激活途径，并显示出与多发性硬化症的潜在共享调控机制。研究结论：高血压与COVID-19的严重病程显著相关。炎症和免疫相关基因中的遗传变异可能影响其在肺部的表达，并赋予高血压和重症COVID-19的易感性。