Impact of chronic oral glucocorticoid treatment on mortality in patients with COVID-19: analysis of a population-based cohort

Abstract

Objectives: While glucocorticoid (GC) treatment initiated for COVID-19 reduces mortality, it is unclear whether GC treatment prior to COVID-19 affects mortality. Long-term GC use raises infection and thromboembolic risks. We investigated if patients with oral GC use prior to COVID-19 had increased mortality overall and by selected causes.

Design: Population-based observational cohort study.

Settings: Population-based register data in Sweden.

Participants: All patients infected with COVID-19 in Sweden from January 2020 to November 2021 (n=1 200 153).

Outcome measures: Any prior oral GC use was defined as ≥1 GC prescription during 12 months before index. High exposure was defined as ≥2 GC prescriptions with a cumulative prednisolone dose ≥750 mg or equivalent during 6 months before index. GC users were compared with COVID-19 patients who had not received GCs within 12 months before index. We used Cox proportional hazard models and 1:2 propensity score matching to estimate HRs and 95% CIs, controlling for the same confounders in all analyses.

Results: 3378 deaths occurred in subjects with any prior GC exposure (n=48 806; 6.9%) and 14 850 among non-exposed (n=1 151 347; 1.3%). Both high (HR 1.98, 95% CI 1.87 to 2.09) and any exposure (1.58, 1.52 to 1.65) to GCs were associated with overall death. Deaths from pulmonary embolism, sepsis and COVID-19 were associated with high GC exposure and, similarly but weaker, with any exposure. High exposure to GCs was associated with increased deaths caused by stroke and myocardial infarction.

Conclusion: Patients on oral GC treatment prior to COVID-19 have increased mortality, particularly from pulmonary embolism, sepsis and COVID-19.

Keywords: COVID-19; adrenal disorders; mortality.

Figure 1

Unadjusted cumulative incidence of all-cause (A) and cause-specific (B–F) mortality among COVID-19 patients in Sweden with any prior exposure* to oral glucocorticoids compared with non-exposed, from COVID-19 infection date to 30 November 2021. GC, glucocorticoids. *Any prior GC exposure equals ≥1 prescription of oral GC within 12 months before the COVID-19 infection date.

Figure 2

Unadjusted cumulative incidence of all-cause (A) and cause-specific (B–F) mortality among COVID-19 patients with high exposure* to oral glucocorticoids compared with non-exposed, from COVID-19 infection date to 30 November 2021. GC, glucocorticoids. *High GC exposure equals ≥2 prescriptions with a total of ≥750 mg of prednisolone or equivalent within 6 months before COVID-19 infection date. This group is a subset of any prior exposure (see figure 1).

Figure 3

Adjusted Cox regression analysis and PS-matched analysis comparing the risk of all-cause and cause-specific mortality between COVID-19 patients with prior exposure to oral glucocorticoids and non-exposed patients. GC, glucocorticoids; ICU, intensive care unit; PS, propensity score. Covariates=age, sex, education, employment and previous medical history (diabetes, deep vein thrombosis, pulmonary embolism, hypertension, stroke, ischaemic heart disease, heart failure, cancer, chronic obstructive pulmonary disease, rheumatological conditions and oral anticoagulation therapy. Any prior GC exposure equals ≥1 prescription of oral GC within 12 months before the COVID-19 infection date. High GC exposure equals ≥2 prescriptions with a total of ≥750 mg of prednisolone or equivalent within 6 months before COVID-19 infection date. The latter group is a subset of any prior exposure. *Adjusted for covariates; †PS matched on covariates. Note: Unadjusted estimates are mentioned in online supplemental table S8.