Wu Weizhen, Zhang Junning, Qiao Yizhuo, Ren Yuehan, Rao Xuezhi, Xu Zhijie, Liu Baoxing
Graduate School, Beijing University of Chinese Medicine, Beijing, China.
Department of Andrology, China-Japan Friendship Hospital, Beijing, China.
Front Cardiovasc Med. 2024 Mar 8;11:1327497. doi: 10.3389/fcvm.2024.1327497. eCollection 2024.
Pre-eclampsia and eclampsia are among the major threats to pregnant women and fetuses, but they can be mitigated by prevention and early screening. Existing observational research presents conflicting evidence regarding the causal effects of coronavirus disease 2019 (COVID-19) on pre-eclampsia risk. Through Mendelian randomization (MR), this study aims to investigate the causal effect of three COVID-19 severity phenotypes on the risk of pre-eclampsia and eclampsia to provide more rigorous evidence.
Two-sample MR was utilized to examine causal effects. Summary-level data from genome-wide association studies (GWAS) of individuals of European ancestry were acquired from the GWAS catalog and FinnGen databases. Single-nucleotide polymorphisms associated with COVID-19 traits at < 5 × were obtained and pruned for linkage disequilibrium to generate instrumental variables for COVID-19. Inverse variance weighted estimates were used as the primary MR results, with weighted median and MR-Egger as auxiliary analyses. The robustness of the MR findings was also evaluated through sensitivity analyses. Bonferroni correction was applied to primary results, with a < 0.0083 considered significant evidence and a within 0.083-0.05 considered suggestive evidence.
Critical ill COVID-19 [defined as hospitalization for COVID-19 with either a death outcome or respiratory support, OR (95% CI): 1.17 (1.03-1.33), = 0.020] and hospitalized COVID-19 [defined as hospitalization for COVID-19, OR (95% CI): 1.10 (1.01-1.19), = 0.026] demonstrated suggestive causal effects on pre-eclampsia, while general severe acute respiratory syndrome coronavirus 2 infection did not exhibit a significant causal effect on pre-eclampsia. None of the three COVID-19 severity phenotypes exhibited a significant causal effect on eclampsia.
Our investigation demonstrates a suggestive causal effect of genetic susceptibility to critical ill COVID-19 and hospitalized COVID-19 on pre-eclampsia. The COVID-19 severity exhibited a suggestive positive dose-response relationship with the risk of pre-eclampsia. Augmented attention should be paid to pregnant women hospitalized for COVID-19, especially those needing respiratory support.
子痫前期和子痫是对孕妇和胎儿的主要威胁之一，但可通过预防和早期筛查来减轻。现有观察性研究关于2019冠状病毒病（COVID-19）对子痫前期风险的因果效应呈现出相互矛盾的证据。通过孟德尔随机化（MR），本研究旨在调查三种COVID-19严重程度表型对子痫前期和子痫风险的因果效应，以提供更严谨的证据。
采用两样本MR来检验因果效应。从全基因组关联研究（GWAS）目录和芬兰基因数据库获取欧洲血统个体的汇总水平数据。获得与COVID-19性状相关的单核苷酸多态性（<5×），并对其进行连锁不平衡修剪，以生成COVID-19的工具变量。采用逆方差加权估计作为主要的MR结果，加权中位数和MR-Egger作为辅助分析。还通过敏感性分析评估MR结果的稳健性。对主要结果应用Bonferroni校正，<0.0083被视为显著证据，0.083 - 0.05被视为提示性证据。
重症COVID-19（定义为因COVID-19住院且伴有死亡结局或呼吸支持，比值比[OR]（95%置信区间）：1.17（1.03 - 1.33），P = 0.020）和住院COVID-19（定义为因COVID-19住院，OR（95%置信区间）：1.10（1.01 - 1.19），P = 0.026）对子痫前期显示出提示性因果效应，而一般严重急性呼吸综合征冠状病毒2感染对子痫前期未显示出显著因果效应。三种COVID-19严重程度表型均未对子痫显示出显著因果效应。
我们的调查表明，对重症COVID-19和住院COVID-19的遗传易感性对子痫前期有提示性因果效应。COVID-19严重程度与子痫前期风险呈现出提示性正剂量反应关系。应更加关注因COVID-19住院的孕妇，尤其是那些需要呼吸支持的孕妇。
