Background: Studies of hospitalized COVID-19 patients suggest increased risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE). The incidence and determinants of these events after COVID-19 diagnosis in the ambulatory setting is less clear.
Objectives: To estimate the risk of ATE and VTE among patients with ambulatory-diagnosed COVID-19 before and during COVID-19 vaccine availability compared to patients with ambulatory-diagnosed influenza.
Methods: We conducted a retrospective cohort study with claims data in the US FDA Sentinel System: 2 national insurers, 4 integrated delivery systems. Patients were ≥18 years old with COVID-19 (pre-vaccine Apr-Oct 2020; post-vaccine Dec 2020-May 2021) or influenza (Oct 2018-Apr 2019) identified via ICD-10 diagnosis or positive PCR test. We estimated 90-day absolute risk of hospitalized ATE (myocardial infarction, stroke) and hospitalized VTE (pulmonary embolism, deep vein thrombosis) via diagnosis codes. We assessed mortality within 30 days of ATE or VTE. We calculated propensity scores to account for cohort differences and used weighted Cox regression to estimate adjusted hazard ratios (HRs) of outcomes with 95% confidence intervals for COVID-19 vs influenza. We identified baseline characteristics associated with ATE and VTE after COVID-19 via multivariable Cox regression.
Results: There were 272,065 patients with COVID-19 pre-vaccine, 342,103 post-vaccine, and 118,618 patients with influenza. The 90-day risk of ATE was 1.01% (0.97-1.05%) for COVID-19 pre-vaccine, 1.06% (1.03-1.10%) post-vaccine, and 0.45% (0.41-0.49%) for influenza. Risk of ATE was higher for COVID-19 vs influenza: HR 1.53 (1.38-1.69) pre-vaccine; HR 1.69 (1.53-1.86) post-vaccine. After ATE, 30-day risk of death was higher for COVID-19 vs influenza: HR 2.65 (1.88-3.73) pre-vaccine; HR 2.53 (1.82-3.51) post-vaccine. The 90-day risk of VTE was 0.73% (0.70-0.77%) for COVID-19 pre-vaccine, 0.88% (0.84-0.91%) post-vaccine, and 0.18% (0.16-0.21%) for influenza. Risk of VTE was higher for patients with COVID-19 vs influenza: HR 2.86 (2.46-3.32) pre-vaccine; HR 3.56 (3.08-4.12) post-vaccine. After VTE, 30-day risk of death was higher for COVID-19 vs influenza: HR 2.36 (1.34-4.18) pre-vaccine; HR 2.58 (1.48-4.50) post-vaccine. Factors associated with higher risk of both ATE and VTE after COVID-19 included older age, male sex, chronic kidney disease, diabetes, heart failure, and hypertension.
Conclusions: Ambulatory-diagnosed COVID-19 patients had a higher risk of hospitalized ATE and VTE before and after vaccine availability vs influenza patients. Some baseline factors were associated with both ATE and VTE among COVID-19 patients and could be used to stratify risk.
