AUTHOR=Cai Lei , He Chuan , Liu Yonglin , Sun Yanlan , He Lin , Baranova Ancha TITLE=Inflammation and immunity connect hypertension with adverse COVID-19 outcomes JOURNAL=Frontiers in Genetics VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.933148 DOI=10.3389/fgene.2022.933148 ISSN=1664-8021 ABSTRACT=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 (RR) of hypertension on mortality and severity of COVID-19 were 1.80 [95% confidence interval (CI) 1.54-2.1] and 1.78 (95% CI 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 to 9.55) with no heterogeneity found (P = 0.26). The genes in 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.