DARWIN EU® EHDS Use Case: Natural history of coagulopathy in COVID-19 patients and persons vaccinated against SARS-CoV-2 in the context of the OMICRON variant

Study type

• Study type:
  Non-interventional study

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (J07BN) Covid-19 vaccines

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  18890000

Study design details

• Main study objective:
  To estimate the background incidence rate of venous and arterial thromboembolic events among the general pre-pandemic population. To estimate the incidence rate of venous and arterial thromboembolic events among patients with COVID-19 within 30-, 60-, and 90- and 180-days during the Omicron period
• Outcomes:
  Venous thromboembolic events: In the primary analysis, venous thromboembolic events will be identified by diagnostic codes for pulmonary embolism or deep vein thrombosis. Arterial thromboembolic events: In the primary analysis, arterial thromboembolic events will be identified by diagnostic codes for an acute myocardial infarction or acute ischemic stroke. ; Venous thromboembolic events: In a secondary analysis pulmonary embolism and deep vein thrombosis will be assessed separately. We will also assess portal vein thrombosis, splanchnic venous thrombosis (SVT) and cerebral venous sinus thrombosis separately. Arterial thromboembolic events: In a secondary analysis acute myocardial infarction and acute ischemic stroke will be assessed separately.
• Data analysis plan:
  Objective 1 - 3: We will use Poisson models to estimate incidence rates and 95% confidence interval. Overall, age group, and sex specific rates will be reported. Within each age-sex strata, rates by prior COVID-19 diagnosis, prior vaccination status and brand, and whether patients are immunosuppressed will be reported as well when event number is larger than 5 within the strata. ; Objective 4a: To assess the association between potential risk factors on the incidence of venous and arterial thromboembolic events among patients with COVID-19 during the Omicron period, cause-specific Cox models will be used to calculate hazard ratios for the incidence of venous and arterial thromboembolic events for each of the COVID-19 cohorts. Adjusted models will evaluate potential predictors including age, sex, prior COVID-19 infection status, prior vaccination status and brand, cancer, whether patients were immunocompromised on the index date, prior use of antithrombotics, prior use of corticosteroids.