A large study from Singapore suggests that COVID-19 infection increased the risk of new-onset cardiovascular and cerebrovascular complications during the Delta variant era and that vaccination lowered the risk.
For the study, published today in Clinical Infectious Diseases, a team led by National Centre for Infectious Diseases researchers used national testing and healthcare claims databases to evaluate the risk and rates of incident cardiovascular (eg, abnormal heart rhythms), cerebrovascular (eg, stroke), and other thrombotic (blood clot–related) complications among adults.
The 106,012 participants tested positive for COVID-19 from September to November 2021, a period of Delta predominance. The researchers also built a test-negative control group of 1,684,085 COVID-naïve people from April 2020 to December 2022. Median follow-up was 300 days.
The average age of infected participants was 51 years, 80.7% were fully vaccinated, and 10.8% were boosted. About 56% were men, and 68.2% were Chinese.
Full vaccination was considered two doses of the Pfizer/BioNTech or Moderna mRNA COVID-19 vaccine given 3 to 8 weeks apart. In September 2021, Singapore recommended a booster for people ages 60 years and older. By the end of the study period, 94% of the population had received two doses, and 24% had received a third.
Risks lower for patients with mild infections
Relative to controls, COVID-19 survivors were at elevated risk (hazard ratio [HR], 1.16) and excess burden ([EB], 0.70) of new-onset cardiovascular and cerebrovascular conditions. Risks were lower among fully vaccinated (HR, 1.11) and boosted (HR, 1.10) participants. The risks and burdens were higher for hospitalized than for nonhospitalized patients.
COVID-19 survivors weren't at higher risk for all cerebrovascular complications (HR, 1.12), including stroke (HR, 1.06) and temporal ischemic attack (HR, 1.21), but there was a moderate weighted EB per 1,000 infected people (EB, 0.08).
Cardiovascular risks and excess burdens were higher for abnormal heart rhythms (HR, 1.32), specifically, sinus bradycardia ([slow heart rate] HR, 1.64) and other arrhythmias (HR, 1.68) in the infected group.
COVID-19 wasn't positively associated with all inflammatory heart disease ([IHD] HR, 1.04). Nor was it linked to an increased risk of acute coronary disease (HR, 0.96), heart attack (HR, 1.08), ischemic cardiomyopathy (HR, 1.11), or angina (HR, 1.24). But COVID-19 survivors had a moderate weighted excess burden per 1,000 people for angina (EB, 0.11).
There were increased risks of other cardiac disorders (HR, 1.33), including heart failure (HR, 1.28) and nonischemic cardiomyopathy (HR, 1.63).
Risks of other thrombotic complications (HR, 1.22), including pulmonary embolism (HR, 1.13), deep venous thrombosis (HR, 1.12), superficial vein thrombosis (HR, 1.78), and arterial thromboses (HR, 0.82), weren't elevated in COVID-19 survivors.
Vaccination lowered risks
Except for dysrhythmias (HR, 1.20), there was no increased risk of cardiovascular, cerebrovascular, and other thrombotic complications among COVID-19 outpatients. But the risk of complications was relatively high in the hospitalized group, including cerebrovascular complications (HR, 3.23), dysrhythmias (HR, 2.67), IHD (HR, 1.49), other cardiac disorders (HR, 2.63), and other thrombotic disorders (HR, 4.01).
Relative to controls, unvaccinated COVID-19 survivors had higher risks of cardiovascular complications such as IHD (HR, 1.45), dysrhythmias (HR, 2.04), and other heart problems (HR, 1.92). They were also at increased risk for composite outcomes such as cardiovascular, cerebrovascular, or other thrombotic complications (HR, 1.56) and major adverse cardiovascular and cerebrovascular events (HR, 1.51).
Risks increased in a graded fashion according to initial severity; vaccination and boosting significantly attenuated risk.
COVID-19 vaccination and booster doses lowered the risk of incident complications associated in a graded fashion. HRs for the vaccinated COVID-19 survivors were smaller compared with estimates in the main analysis.
"In a national cohort of Delta-infected individuals, increased risk and burden of new-incident cardiovascular/cerebrovascular complications was demonstrated 300 days postinfection," the authors wrote. "Risks increased in a graded fashion according to initial severity; vaccination and boosting significantly attenuated risk."
There were no increased risks of any cardiovascular, cerebrovascular, or other thrombotic complication (HR, 1.10) among third-dose COVID-19 survivors. The only risk of an individual complication in the boosted group was for other arrhythmias (HR, 2.20).
"Chronic inflammation arising from residual viral reservoirs persisting in cardiac tissue or an autoimmune response to cardiac antigens may result in tissue damage and myocardial fibrosis, leading to impaired ventricular contractility and potential reentrant arrhythmias," the researchers wrote. "Virus-induced lung injury may also induce right ventricular dysfunction through increasing pulmonary vascular resistance and right ventricular strain."