Procedures

The index date was considered to be the date of a valid COVID-19 test (infection date or first negative test). For patients with COVID-19, the index date was set to the date of their first positive test; for those without COVID-19, the index date was set to the date of their first negative test. Patients with severe COVID-19 outcomes (ie, hospitalisation, mechanical ventilation, or death) were identified if they were hospitalised (new admission) within the window of 3 days before 14 days of the index date; or received mechanical ventilation or died within 30 days of the index date (figure 1).

For patients with COVID-19, the index date was date of first positive test; for patients without COVID-19, the index date was date of first negative test. IMID=immune-mediated inflammatory disease. IMM=immunomodulatory medication.

Patient use of IMMs was observed for 3 months leading up to the index date to include medications that were administered periodically and had a multiple-month effect on the immune system (figure 1). IMMs were identified by RxNorm medication order codes (appendix pp 20–21). To be able to establish the effect of the use of IMMs at the time of SARS-CoV-2 infection, we selected a subset of patients who had at least one encounter with PSJH before the index date.

Comorbidities and IMIDs were identified by diagnosis codes by use of SNOMED-CT (version obtained on June 27, 2022; appendix pp 18–20). The active status of patient comorbidities and IMIDs was decided based on the index date. COVID-19 vaccination status was decided before the index date. For patients with a COVID-19 vaccine from either Moderna or Pfizer, we counted two administered doses as fully vaccinated and more than two doses as boosted. For patients with a COVID-19 vaccine from Janssen, we counted one administered dose as fully vaccinated and more than one dose as boosted. All vaccination information was obtained from state records and limited to the seven states in our study. If patients only came for a COVID-19 test during the pandemic they would not necessarily have a history taken and any comorbidities, vaccination status, and previous use of IMMs would be recorded as unknown.

Primary outcomes were the combined endpoint of hospitalisation, mechanical ventilation, and death; the combined endpoint of mechanical ventilation and death; and death among patients with COVID-19. Hospitalisation is defined within the window of 3 days before the index date to 14 days after the index date. Mechanical ventilation and death are defined as the window within 30 days after the index date. We assessed differences in the rates of outcomes using Fisher’s exact test.