Long-term Cardiovascular Effects of COVID-19 Infection: A 5-Year Prospective Cohort Study

Background: The SARS-CoV-2 pandemic has affected over 700 million individuals worldwide, with emerging evidence suggesting persistent cardiovascular complications extending beyond acute infection. However, comprehensive long-term cardiovascular outcome data remain limited.

Objective: To characterize the incidence, progression, and clinical significance of cardiovascular complications in individuals recovered from COVID-19 infection over a five-year follow-up period.

Methods: This prospective, multicenter cohort study enrolled 4,582 adults who recovered from laboratory-confirmed COVID-19 infection between March 2020 and September 2020 across medical centers in Sweden, India, and Australia. Participants underwent comprehensive cardiovascular assessment including cardiac biomarkers (high-sensitivity troponin, NT-proBNP), electrocardiography, echocardiography, and cardiac magnetic resonance imaging at baseline (3 months post-infection) and at 6-month intervals through 60 months. Primary outcomes included incident heart failure, myocardial infarction, stroke, arrhythmias, and cardiovascular mortality. Analyses were stratified by initial COVID-19 severity (mild, moderate, severe/critical) and vaccination status.

Results: Over median follow-up of 58.3 months (IQR: 56.1-60.0), 847 participants (18.5%) experienced major adverse cardiovascular events (MACE). Compared to matched controls without prior COVID-19 infection, the cohort demonstrated elevated risk for heart failure (HR 2.47, 95% CI: 2.18-2.79), myocardial infarction (HR 1.83, 95% CI: 1.52-2.21), stroke (HR 1.94, 95% CI: 1.61-2.34), and atrial fibrillation (HR 2.12, 95% CI: 1.84-2.44). Risk stratification by disease severity revealed dose-response relationship, with severe/critical illness associated with 4.2-fold increased cardiovascular risk (HR 4.23, 95% CI: 3.67-4.88). Vaccination prior to infection reduced cardiovascular complications by 41% (HR 0.59, 95% CI: 0.48-0.73).

Conclusion: COVID-19 infection is associated with substantial long-term cardiovascular sequelae persisting for at least five years post-recovery. Disease severity predicts cardiovascular risk, while vaccination demonstrates protective effects. These findings support intensive cardiovascular monitoring for COVID-19 survivors and underscore the importance of preventive vaccination strategies.

Keywords: COVID-19, SARS-CoV-2, cardiovascular disease, long COVID, myocarditis, heart failure, prospective cohort study