Cai Lei, He Chuan, Liu Yonglin, Sun Yanlan, He Lin, Baranova Ancha
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Collaborative Innovation Center for Genetics and Development, Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, China.
Sanya Women and Children's Hospital managed by Shanghai Children's Medical Center, Sanya, China.
Front Genet. 2022 Sep 8;13:933148. doi: 10.3389/fgene.2022.933148. eCollection 2022.
To explore the connection of hypertension and severe COVID-19 outcomes. 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. 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 ( = 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. 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.
为探究高血压与重症新型冠状病毒肺炎(COVID-19)预后之间的关联。共纳入68项记录COVID-19死亡率和/或总体严重程度的观察性研究,对重症COVID-19预后与高血压以及收缩压和舒张压之间的关系进行荟萃分析。进行全基因组跨性状荟萃分析(GWCTM)以探索连接高血压与COVID-19严重程度的基因。随机效应模型的荟萃分析结果表明,高血压对COVID-19死亡率和严重程度的合并风险比分别为1.80[95%置信区间(CI)1.54 - 2.1]和1.78(95%置信区间1.56 - 2.04),尽管纳入研究存在明显异质性。在亚组分析中,欧洲评估的COVID-19重症和轻症患者队列的合并加权平均差为6.61 mmHg(95% CI 3.66 - 9.55),未发现异质性(I² = 0.26)。高血压与COVID-19严重程度共同特征中的基因大多在肺部表达。对受高血压和重症COVID-19共同影响的分子网络分析突出了CCR1/CCR5和IL10RB信号通路,以及Th1和Th2激活途径,还显示出与多发性硬化症共同调节的可能性。高血压与COVID-19的重症病程显著相关。炎症和免疫相关基因内的遗传变异可能影响其在肺部的表达,并使个体易患高血压和重症COVID-19。
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