Association of COVID-19 Infection and SARS-CoV-2 Vaccination With Echocardiographic Pericardial Involvement in a Real-World Outpatient Cohort

Background During the COVID‑19 pandemic, inflammatory myopericardial syndromes have been reported following SARS‑CoV‑2 infection and SARS‑CoV‑2 vaccination. However, the prevalence of such conditions in routine clinical practice, including mild or residual pericardial alterations, remains incompletely characterized. This study aimed to evaluate the association between prior SARS-CoV-2 infection, SARS-CoV-2 vaccination, and echocardiographic pericardial involvement in a real-world outpatient cohort undergoing routine transthoracic echocardiography. Methods This retrospective cohort study analyzed 1,431 consecutive patients undergoing routine outpatient echocardiography from 2018 to 2022 at the Istituto di Medicina Biologica di Milano, Milan, Italy. Pericardial involvement was defined as echocardiographic findings consistent with pericardial inflammation, including pericardial effusion, thickening, hyperechogenicity, and fibrinous strands, encompassing not only clinically evident pericarditis but also minimal pericardial alterations and residual findings. Multivariable logistic regression and average marginal effects were used to assess associations with prior COVID‑19 infection, SARS‑CoV‑2 vaccination status, age, sex, and BMI, adjusting for calendar year and confounders. Results Pre‑pandemic pericardial involvement was detected in 101/459 (22%) examinations (2018-2019), rising to 463/673 (68.8%) during the pandemic years (2020-2022; P < 0.001). Both prior COVID‑19 infection (odds ratio (OR) 1.99, 95% confidence interval (CI) 1.17-3.43, P = 0.012) and vaccination (OR 2.08, 95% CI 1.29-3.35, P = 0.003) were independently associated with pericardial involvement, with a significant interaction suggesting that prior infection attenuated additional risk from vaccination, and vice versa. Female sex, older age, and higher BMI were also associated with higher odds. Conclusions In this real-world echocardiography cohort, both SARS-CoV-2 infection and vaccination were associated with increased odds of echocardiographic pericardial involvement, including minimal and residual alterations. The marked temporal rise during the pandemic may reflect a combination of subclinical inflammatory changes and evolving referral and diagnostic practices, while the absolute risk of vaccine-associated myopericarditis remained low compared with the overall benefits of vaccination.