Thromboembolism After COVID-19 vs. Influenza

Two and a half years into the COVID-19 pandemic, it’s become clear that the disease can continue to take a far-reaching toll on the body long after the initial sore throat and coughing has subsided. One outcome of infection is an increase in hypercoagulability, with thromboembolism a threat in the weeks and months after a person is hospitalized with COVID-19.

While several studies have examined the incidence of thrombotic complications following COVID-19 infection, up until now these studies have been small and have not included other cohorts for comparison. A team of scientists at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia conducted a retrospective cohort study designed to compare the 90-day risks of arterial and venous thromboembolism in patients hospitalized with COVID-19 compared with patients hospitalized with influenza, as influenza is known to be a risk factor for embolic events. COVID-positive patients were evaluated for thromboembolism in the time period before COVID-19 vaccines were available (April 2020-November 2020) and during vaccine availability (December 2020-April 2021), while influenza patients were assessed between 2018 and 2019. The study was published in JAMA.

The study, which included 85,637 patients hospitalized with COVID-19 and 8,269 patients hospitalized with influenza, found that the 90-day absolute risk of venous thromboembolism in patients who’d had COVID-19 was significantly higher than in those who’d had influenza. Hospitalized influenza patients had a 90-day risk of venous thromboembolism of 5.3% (95% confidence interval, 4.9%-5.9%) versus 9.5% (95% CI, 9.2-9.7) in COVID-19 patients before vaccines were available and 10.9% (95% CI, 10.6%-11.1%) in COVID-19 patients during vaccine availability.

In contrast, while the incidence of arterial thromboembolism was higher than that of venous thromboembolism overall, little difference in arterial thromboembolism risk was found between hospitalized COVID-19 patients and hospitalized influenza patients. The 90-day risk of arterial thromboembolism in influenza patients was 14.4% (95% CI, 13.6%-15.2%) compared with 15.8% (95% CI, 15.5%-16.2%) in COVID-19 patients pre-vaccine availability and 16.3% (95% CI, 16.0-16.6) during the time vaccines were distributed.

Venous and arterial thromboembolism are quite distinct processes triggered by different mechanisms, the authors explain. “SARS-CoV-2 infection of endothelial cells incites inflammation and abnormalities in coagulation (ie, increased concentrations of D-dimer, antiphospholipid antibodies; decreased concentrations of anticoagulant proteins; increased platelet activity), and these abnormalities might have more of an effect on risk of venous than arterial thromboembolism and may be more marked for COVID-19 than influenza,” Vincent Lo Re, MD, MSCE, associate professor of medicine at the Perelman School of Medicine and an author of the study, told Contagion.

The risk of arterial thromboembolism was higher in hospitalized COVID-19 vs. influenza patients in 1 particular group, however: those with existing cardiovascular disease. The 90-day risk of arterial thromboembolism in hospitalized COVID-19 patients with cardiovascular disease was 21% before vaccines were available and 21.3% during vaccine availability. For patients hospitalized with influenza, the risk was 18.2%. While the exact reason for the higher arterial thromboembolism risk in COVID-19 patients with cardiovascular disease is not clear, Lo Re suggested it may have to do with the microvascular and macrovascular changes that occur with cardiovascular disease.

COVID-19 patients without a history of venous thromboembolism had a significantly elevated risk of venous thromboembolism in the 90-day follow-up period compared with influenza patients, both before and during COVID-19 vaccine availability. Interestingly, for those who had a history of venous thromboembolism, the risk of a venous thrombotic event was not significantly higher in COVID-19 vs. influenza patients before vaccines were available yet was significantly higher during vaccine availability.

Lo Re explained that these discrepancies could have to do with therapies dispensed prior to hospitalization. “Patients with venous thromboembolism history might…have been more likely to receive intermediate or treatment doses of anticoagulant therapy during their hospitalization, although inpatient therapies could not be captured with this data,” he said. “Patients without a history of VTE likely were not prescribed anticoagulant therapy that could have mitigated the development of these events.”

The study findings underscore that there are real differences between influenza and COVID-19 that place patients hospitalized with COVID-19 at greater risk for venous thromboembolism. Patients with COVID-19 who are admitted to the hospital and are at high risk for venous thromboembolism should be closely monitored to potentially prevent this complication.