Key result
Genetically predicted severe COVID-19 was not causally associated with an increased risk of myocarditis (OR 1.00) or pericarditis in individuals of European descent.
Why the study?
Observational studies show conflicting results regarding the association of COVID-19 with myocarditis or pericarditis, leaving whether the association reflects causation unconfirmed.
Does genetically predicted COVID-19 increase the risk of myocarditis or pericarditis in individuals of European ancestry?
Observational (n=2,597,856)
Mendelian randomization
Does genetically predicted COVID-19 increase the risk of myocarditis or pericarditis in individuals of European ancestry?
Odds Ratio: 1 (95% CI 0.89–1.12)
p-value: p=0.99
This bidirectional Mendelian randomization study found no evidence that COVID-19 is independently and causally associated with an increased risk of myocarditis or pericarditis.
No causal link in Europeans; challenges observational reports and leaves open non-genetic factors or other ancestries.
Background & aims 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. Methods 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. Results 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. Conclusion There is no evidence that COVID-19 is independently and causally associated with myocarditis or pericarditis.
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Liu et al. (2023) conducted an observational in COVID-19, myocarditis, pericarditis (n=2,597,856). Genetically predicted COVID-19 vs. Controls without COVID-19 was evaluated on Myocarditis (OR 1.00, 95% CI 0.89-1.12, p=0.99). Genetically predicted severe COVID-19 was not causally associated with an increased risk of myocarditis (OR 1.00) or pericarditis in individuals of European descent.
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