Background: Preliminary evidence from single-institution data suggests no increased risk of COVID-19 related ventilation or death with chronic immunosuppression.

Objectives: We used a large, national and diverse dataset of individuals hospitalized with COVID-19 in the United States to evaluate the association between chronic pharmacologic immunosuppression with inpatient COVID-19 outcomes.

Methods: We used the National COVID Cohort Collaborative (N3C), an electronic health record (EHR) repository in the United States. Our cohort included individuals hospitalized in 33 health system from January 2020 through February 2021 with a positive COVID test up to 21 days before or 5 days after admission. We defined chronic immunosuppression as persons with immunosuppressive drugs (WHO ATC group L01 or L04) active in the EHR upon admission. Glucocorticoids were included as an immunosuppressant if use predated COVID diagnosis and the person had a diagnosis of psoriasis, ulcerative colitis, rheumatoid arthritis, COPD or asthma. All other persons were considered non-immunosuppressed. Outcomes were invasive mechanical ventilation or death during hospitalization. We used Cox proportional hazards models to calculate the hazard ratios (HR) with 95% confidence intervals (95% CI), adjusted for age, sex, BMI, smoking status and each comorbidity in the Charlson Index.

Results: We identified 78,378 people hospitalized with COVID, with 9,909 (13%) immunosuppressed before COVID, most often by prednisone, mycophenolate mofetil or tacrolimus. The risk of invasive ventilation did not differ by immune system status (13% immunosuppressed vs 12% non-immunosuppressed, HR=1.06, 95% CI 0.989-1.14). There was an increased risk of death among immunosuppressed persons (16% vs 12%), which was attenuated with statistical adjustment (HR=1.03, 95% CI 0.97-1.10). In sub-group analyses restricted to immunosuppressed persons, calcineurin inhibitors were associated with a lower risk of invasive mechanical ventilation (HR=0.84, 95% CI 0.71-0.98) and death (HR=0.70, 95% CI 0.60-0.82) than other immunosuppressant classes.

Conclusions: Immunosuppressed persons were not at an increased risk of invasive ventilation or death as compared to otherwise similar hospitalized COVID-19 patients. The large sample size allowed us to look at subclasses of immunosuppression, where we found differences in drugs used for solid organ transplant. Work is ongoing to understand if these associations persist in propensity-score weighted models, which will account for confounding variables and competing risks.