ABSTRACT
BackgroundTocilizumab, a drug targeting interleukin-6 administrated in the right timeframe may be beneficial in coronavirus-disease-2019 (COVID-19). We aimed to assess its benefit, drawing from observations in compassionately treated patients. MethodsIn a retrospective case-control study, treatment effect (tocilizumab 400mg, single-dose) was assessed using three statistical methods: propensity-score matching, Cox multivariable survival and inverse probability score weighting (IPSW) analyses. Were included all patients hospitalized with COVID-19, who presented severity criteria with SpO2[≤]96% despite O2-support [≥]6L/min for more than 6 hours. Were excluded patients in critical care medicine department and those under invasive mechanical ventilation. Primary outcome was a composite of mortality and ventilation, with a maximum follow-up of 28 days. Results246 patients were included (106 treated by tocilizumab). They were 67.6 {+/-}15.3 years-old, with 95 (38.5%) women. Delay between first symptoms and inclusion was 8.4 {+/-}4.5 days. Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-days follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes (hazard ratio (HR) = 0.49 (95% confidence interval (95CI) = 0.3-0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95CI = 0.135-0.51, p = 0.0001), confirmed by IPSW analysis (p<0.0001). Analyses on mortality with 28-days follow-up yielded similar results. ConclusionIn this retrospective study, tocilizumab single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.
ABSTRACT
BackgroundPrognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward. MethodsFrench single-center prospective cohort study of 152 patients with positive Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay, hospitalized in a medical ward. Multivariable models and a simplified scoring system assessed predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death). A validation was performed on an external sample of 132 patients. FindingsAt D14, the probability of ICU transfer or death was 32% (95% CI 25-40). Older age (OR 2{middle dot}61, 95% CI 0{middle dot}96-7{middle dot}10), poorer respiratory presentation (OR 4{middle dot}04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1{middle dot}76-9{middle dot}25), higher CRP-level (OR 1{middle dot}63 per 100mg/L increment, 95% CI 0{middle dot}98-2{middle dot}71) and lower lymphocytes count (OR 0{middle dot}36 per 1000/mm3 increment, 95% CI 0{middle dot}13-0{middle dot}99) were associated with an increased risk of ICU requirement or death. A 8-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. InterpretationIn this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, 32% were transferred to ICU or died. A simplified scoring system at admission predicted the outcome at D14. FundingNo funding.
