■在观察性研究中,2019年冠状病毒病(COVID-19)与心肌炎或心包炎风险密切相关,然而,仍有研究不支持上述结论。观察到的关联是否反映了因果关系需要确认。我们进行了双向孟德尔随机(MR)研究,以评估COVID-19的因果关系,分为三组,即重症COVID-19、住院COVID-19和COVID-19感染,由心肌炎或心包炎测量。
■我们提取了严重COVID-19的全基因组关联统计摘要(病例:13,769,对照:1,072,442),住院COVID-19(病例:32,519,对照:2,062,805),COVID-19感染(病例:122,616,对照:2,475,240),心肌炎(病例1,521,对照191,924),和心包炎(病例979,对照286,109)在欧洲血统的个体中。在全基因组显著性水平上表现出与每个表型显著关联的独立遗传变异体被用作工具变量。因果效应的估计主要使用随机效应逆方差加权法(IVW)进行。此外,其他测试,如MR-Egger截距,MR-PRESSO,Cochran的Q检验,\"离开一个\",和漏斗图进行评估多效性和异质性的程度。
■在IVW和敏感性分析中观察到COVID-19与心肌炎或心包炎的非关联。重症COVID-19与心肌炎无关[比值比(OR),1.00;95%置信区间(CI),0.89-1.12;P=0.99],心包炎(OR=0.90,95%CI,0.78~1.04,P=0.17)。在住院的COVID-19和COVID-19感染中也可以观察到类似的结果。同时,心肌炎或心包炎与COVID-19性状的反向相关性为零。在敏感性分析中,主要结果保持稳定。
■没有证据表明COVID-19与心肌炎或心包炎有独立和因果关系。
UNASSIGNED: Coronavirus disease 2019 (COVID-19) is strongly associated with myocarditis or pericarditis risk in observational studies, however, there are still studies that do not support the above conclusion. Whether the observed association reflects causation needs to be confirmed. We performed a bidirectional Mendelian randomization (MR)
study to assess the causal relationship of COVID-19, which was divided into three groups, namely severe COVID-19, hospitalized COVID-19, and COVID-19 infection, measured by myocarditis or pericarditis.
UNASSIGNED: We extracted summary genome-wide association statistics for the severe COVID-19 (case: 13,769, control: 1,072,442), hospitalized COVID-19 (case: 32,519, control: 2,062,805), COVID-19 infection (case: 122,616, control: 2,475,240), myocarditis (case 1,521, control 191,924), and pericarditis (case 979, control 286,109) among individuals of European ancestry. Independent genetic variants that exhibited a significant association with each phenotype at the genome-wide level of significance were utilized as instrumental variables. Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Additionally, other tests such as MR-Egger intercept, MR-PRESSO, Cochran\'s Q-test, \"Leave-one-out\", and funnel plots were conducted to assess the extent of pleiotropy and heterogeneity.
UNASSIGNED: Non-associations in the IVW and sensitivity analyses were observed for COVID-19 with myocarditis or pericarditis. Severe COVID-19 was not associated with myocarditis [odds ratio (OR), 1.00; 95% confidence interval (CI), 0.89-1.12; P = 0.99], pericarditis (OR = 0.90, 95% CI, 0.78-1.04, P = 0.17). Similar results can be observed in hospitalized COVID-19, and COVID-19 infection. At the same time, null associations were observed for myocarditis or pericarditis with COVID-19 traits in the reverse direction. The main results are kept stable in the sensitivity analysis.
UNASSIGNED: There is no evidence that COVID-19 is independently and causally associated with myocarditis or pericarditis.