Tocilizumab, an anti-interleukin-6 receptor, administrated during the right timeframe may be beneficial against coronavirus-disease-2019 (COVID-19) pneumonia. All patients admitted for severe COVID-19 pneumonia (SpO₂ ≤ 96% despite O₂-support ≥ 6 L/min) without invasive mechanical ventilation were included in a retrospective cohort study in a primary care hospital. The treatment effect of a single-dose, 400 mg, of tocilizumab was assessed by comparing those who received tocilizumab to those who did not. Selection bias was mitigated using three statistical methods. Primary outcome measure was a composite of mortality and ventilation at day 28. A total of 246 patients were included (106 were treated with tocilizumab). Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-day follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes than the control group (hazard ratio (HR) = 0.49 (95% confidence interval (95%CI) = 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 (95%CI = 0.135–0.51, p = 0.0001), confirmed by inverse probability score weighting (IPSW) analysis (p < 0.0001). Analyses on mortality only, with 28 days of follow-up, yielded similar results. In this study, tocilizumab 400 mg in a single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.

This work’s objective was to evaluate the safety of isavuconazole (ISA) as a treatment or prophylaxis for invasive fungal infections (IFIs) in immunocompromised children. IFI was reported as proven or probable according to international definitions. Therapeutic drug monitoring was performed using mass tandem spectrometry to quantify trough plasma concentrations. Targeted ISA levels were 2–4 mg/L, as reported in adult series. Nine patients received ISA as a curative treatment, and six received ISA as prophylaxis. IFIs were proven in four cases and probable in five. The median ISA trough plasma concentration in curative use was 3.19 mg/L [0.88;5.00], and it was 2.94 mg/L [2.77;3.29] in the prophylactic use. The median durations of treatment were 81 days [15;276] and 95 days [15;253], respectively. Three patients had elevated aspartate aminotransferase and alanine aminotransferase, and three patients had elevated creatinine serum. The IFI response was satisfactory in all cases at day 90. No side effects were reported. No patients developed an IFI. Our data underline the safety of an ISA 100 mg dosing regimen in children of <30 kg, which we recommend in this fragile population. We suggest that ISA plasma levels are monitored 10 days after ISA initiation and then every two weeks, alongside guided therapeutic drug monitoring (TDM) administration.

Background: Tocilizumab, 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. Methods: In 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. Results: 246 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. Conclusion: In this retrospective study, tocilizumab single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.