Third, we included only people who were hospitalised for at least 2 days, because individuals discharged the same or next day might be clinically distinct from those with longer stays. In a second sensitivity analysis, we restricted the cohort to individuals with at least one previous health system encounter before COVID-19 diagnosis, to assess whether the lack of lookback data could have affected covariate ascertainment. We did a sensitivity analysis to assess whether the absence of glucocorticoid dose information could create exposure misclassification by excluding individuals who had a record of glucocorticoid use without any dose information. People without use of any of the immunosuppressive drugs on the date of admission were considered non-immunosuppressed. For oral glucocorticoids, we further required a diagnosis that was consistent with long-term use of steroids (appendix p 15). We excluded 57 people whose only immunosuppressant was a glucocorticoid prescribed on or after the date of COVID-19 diagnosis but before admission. We classified people as having long-term immunosuppression at the time of admission if they used one or more of these medications in addition, we used the electronic health record fields of prescription record start and stop dates, and we required immunosuppression to be started at least 14 days before the date of admission, and either continued during admission or actively stopped on or after the date of admission. Individuals were considered immunosuppressed if they had exposure to at least one of the following: rheumatological drugs (interleukin inhibitors, Janus kinase inhibitors, tumour necrosis factor (TNF) inhibitors, or any other drug in the WHO Anatomical Therapeutic Chemical L04: selective immunosuppressants), antimetabolite drugs (azathioprine, calcineurin inhibitors, or mycophenolic acid ), cancer therapies (anthracyclines, checkpoint inhibitors, cyclophosphamide, protein kinase inhibitors, or any other drug in the WHO ATC class L01: antineoplastic agents), rituximab, targeted cancer therapies, and oral glucocorticoids (dexamethasone, prednisone, prednisolone, or methylprednisolone appendix pp 2–4). We defined two mutually exclusive exposure groups: immunosuppressed individuals and non-immunosuppressed individuals up to and including at the time of admission. Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions. Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1♷2, 1♱0–2♶9) and for cancer (2♵7, 1♸6–3♵6). None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation. In the propensity score matched cohort (including 12 841 immunosuppressed patients and 29 386 non-immunosuppressed patients), immunosuppression was associated with a reduced risk of invasive ventilation (HR 0♸9, 95% CI 0♸3–0♹6) and there was no overall association between long-term immunosuppression and the risk of in-hospital death. 16 494 (7%) patients had long-term immunosuppression with medications for diverse conditions, including rheumatological disease (33%), solid organ transplant (26%), or cancer (22%). The most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). The Lancet Regional Health – Western PacificĪmong 231 830 potentially eligible adults in the N3C repository who were admitted to hospital with confirmed or suspected COVID-19 during the study period, 222 575 met the inclusion criteria (mean age 59 years 111 269 male).The Lancet Regional Health – Southeast Asia.The Lancet Gastroenterology & Hepatology.
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