Objective Patients treated with long-term opioid therapy (LTOT) are known to have compromised immune systems and respiratory function, both of which make them particularly susceptible to the SARS-CoV-2 virus. The objective of this study was to assess the risk of developing severe clinical outcomes among COVID-19 non-cancer patients on LTOT, compared with those without LTOT. Design and data sources A retrospective cohort design using electronic health records in the TriNetX research database. Participants and setting 418 216 adults diagnosed with COVID-19 in January-December 2020 from 51 US healthcare organisations: 9558 in the LTOT and 408 658 in the control cohort. They did not have cancer diagnoses; only a small proportion might have been treated with opioid maintenance for opioid use disorder. Results Patient on LTOT had a higher risk ratio (RR) than control patients to visit an emergency department (RR 2.04, 95% CI 1.93 to 2.16) and be hospitalised (RR 2.91, 95% CI 2.69 to 3.15). Once admitted, LTOT patients were more likely to require intensive care (RR 3.65, 95% CI 3.10 to 4.29), mechanical ventilation (RR 3.47, 95% CI 2.89 to 4.15) and vasopressor support (RR 5.28, 95% CI 3.70 to 7.53) and die within 30 days (RR 1.96, 95% CI 1.67 to 2.30). The LTOT group also showed increased risk (RRs from 2.06 to 3.98, all significant to 95% CI) of more-severe infection (eg, cough, dyspnoea, fever, hypoxaemia, thrombocytopaenia and acute respiratory distress syndrome). Statistically significant differences in several laboratory results and other vital signs appeared clinically negligible. Conclusion COVID-19 patients on LTOT were at higher risk of increased morbidity, mortality and healthcare utilisation. Interventions to reduce the need for LTOT and to increase compliance with COVID-19 protective measures may improve outcomes and reduce healthcare cost in this population. Prospective studies need to confirm and refine these findings.
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