Long-term Cardiovascular, Cerebrovascular, and Other Thrombotic Complications in COVID-19 Survivors: A Retrospective Cohort Study

Abstract

Background: Growing evidence suggests that some coronavirus disease 2019 (COVID-19) survivors experience a wide range of long-term postacute sequelae. We examined the postacute risk and burden of new-incident cardiovascular, cerebrovascular, and other thrombotic complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a highly vaccinated multiethnic Southeast Asian population, during Delta predominance.

Methods: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals who had a positive SARS-CoV-2 test between 1 September and 30 November 2021 when Delta predominated community transmission. Concurrently, we constructed a test-negative control group by enrolling individuals between 13 April 2020 and 31 December 2022 with no evidence of SARS-CoV-2 infection. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular, cerebrovascular, and other thrombotic complications using doubly robust competing-risks survival analysis. Risks were reported using 2 measures: hazard ratio (HR) and excess burden (EB) with 95% confidence intervals.

Results: We included 106 012 infected cases and 1 684 085 test-negative controls. Compared with the control group, individuals with COVID-19 exhibited increased risk (HR, 1.157 [1.069-1.252]) and excess burden (EB, 0.70 [.53-.88]) of new-incident cardiovascular and cerebrovascular complications. Risks decreased in a graded fashion for fully vaccinated (HR, 1.11 [1.02-1.22]) and boosted (HR, 1.10 [.92-1.32]) individuals. Conversely, risks and burdens of subsequent cardiovascular/cerebrovascular complications increased for hospitalized and severe COVID-19 cases (compared to nonhospitalized cases).

Conclusions: Increased risks and excess burdens of new-incident cardiovascular/cerebrovascular complications were reported among infected individuals; risks can be attenuated with vaccination and boosting.

Keywords: cardiovascular; cerebrovascular; complications; postacute sequelae of SARS-CoV-2 infection; thrombotic.

Figure 1.

Flowchart of cohort construction. Abbreviations: ARI, acute respiratory illness; COVID-19, coronavirus disease 2019; PHPCs, Public Health Preparedness Clinics; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; T₀, index date of infection.

Figure 2.

Hazard ratios (HRs) and 95% confidence intervals (CIs) for composite cardiovascular, cerebrovascular, and other thrombotic complications according to severity, vaccination, main cohort, sex, and age group (in years). Points and lines represent point estimates for HRs and 95% CIs, respectively. Blank points represent inestimable HRs due to null counts in that specific subgroup for cases, controls, or both. Abbreviations: CI, confidence interval; COVID, coronavirus disease 2019; HR, hazard ratio.