Does timing of tocilizumab administration affect mortality in COVID-19? A Scottish multicentre retrospective cohort study.

BACKGROUND: The optimal timing of tocilizumab treatment during the disease course of COVID-19 has yet to be adequately defined in the context of randomised controlled trials and the effect of tocilizumab on real-world populations remains unclear. We examined the effect of different timing of tocilizumab, on mortality, in a cohort of adults with COVID-19. METHODS: All adults (≥18 years old) with confirmed COVID-19 admitted to four hospitals in the West of Scotland between 8 January 2021 and 31 March 2021 and who received tocilizumab were included in a retrospective observational cohort study. Patients were assigned to either an early (day of admission or first day after admission) or late (days 2-7 of admission) cohort based on tocilizumab initiation. The primary outcome was 90-day all-cause mortality in early versus late cohorts. Secondary outcomes were 28 and 180-day all-cause mortality. RESULTS: 203 patients were included in the analysis (138 in the early cohort, 65 in the late cohort). Mortality in 90 days in the early cohort was 22% (n=30) compared with 45% (n=29) in the late cohort (p<0.001). The adjusted mortality was significantly higher in the late cohort compared with the early cohort (adjusted OR: 3.33; 95% CI: 1.29 to 8.54; p=0.012). The secondary outcomes demonstrated the same effect with higher rates of death in 28 days (late cohort adjusted OR: 3.28; 95% CI: 1.23 to 8.75; p=0.018) and 180 days (late cohort adjusted OR: 3.70; 95% CI: 1.45 to 9.45; p=0.006). The effect was seen whether the outcome was adjusted or unadjusted. CONCLUSION: Early administration of tocilizumab within the first 2 days of hospitalisation was associated with a significant survival benefit compared with late exposure. Late administration was associated with particularly high mortality. The observed association may be a result of residual confounders and further research is needed.

Evaluation of medication changes following severe COVID-19 infection: a multicentre evaluation.

BACKGROUND: Critically ill patients often experience several transitions of care following critical illness. Research has explored the challenges which patients have with medication management across these transitions. It is unclear whether patients admitted to critical care due to COVID-19 will have similar challenges. The aim of this study was to explore medication management in critical care survivors following severe COVID-19. METHODS: Between 3 and 7 months post hospital discharge, patients who had been admitted to critical care due to severe COVID-19 were invited to an established recovery service. During the clinic consultation a medication review was performed by a pharmacist. This included medicines reconciliation, assessing the appropriateness of each of the prescribed medications and identification of medication changes. We also assessed changes to pain management in the discharge period. RESULTS: In total, 78 patients had a full medication review available. Over 70% of patients were taking an increased dose of medicine or a new medicine at clinic. There was a significant overall increase in new medication during the clinic consultation, across different British National Formulary classifications (OR: 1.73 (95% CI: 1.28 to 2.34), p<0.001). Compared with pre critical care admission, there was a significant increase in the number of patients taking regular analgesia following severe COVID-19 infection (23 (29.5%) vs 39 (50%), p<0.001). CONCLUSION: Following severe COVID-19, patients may require new or increasing doses of medicines. Ongoing review of these patients is crucial to ensure optimal outcomes.