Anup K. Singh

Treatment with dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia requiring supplemental oxygen, but the optimal dose has not been determined. To determine whether weight-based dexamethasone of 0.2 mg/kg is superior to 6 mg daily in reducing 28-day mortality in patients with COVID-19 and hypoxemia. A multicenter, open-label, randomized clinical trial was conducted between March 2021 and December 2021 at seven hospitals within Northwell Health. A total of 142 patients with confirmed COVID-19 and hypoxemia were included. Participants were randomized in a 1:1 ratio to dexamethasone 0.2 mg/kg intravenously daily (n = 70) or 6 mg daily (n = 72) for up to 10 days. There was no statistically significant difference in the primary outcome of 28-day all-cause mortality with deaths in 12 of 70 patients (17.14%) in the intervention group and 15 of 72 patients (20.83%) in the control group (p = 0.58). There were no statistically significant differences among the secondary outcomes. In patients with COVID-19 and hypoxemia, the use of weight-based dexamethasone dosing was not superior to dexamethasone 6 mg in reducing all-cause mortality at 28 days. This study was registered under ClinicalTrials.gov (identifier: NCT04834375).

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to be a global challenge due to the lack of definitive treatment strategies. We sought to determine the efficacy of early administration of anti-interleukin 6 therapy in reducing hospital mortality and progression to mechanical ventilation. METHODS: This was a retrospective chart review of 11,512 patients infected with SARS-CoV-2 who were admitted to a New York health system from March to May 2020. Tocilizumab was administered to subjects at the nasal cannula level of oxygen support to maintain an oxygen saturation of >88%. The Charlson comorbidity index was used as an objective assessment of the burden of comorbidities to predict 10-year mortality. The primary outcome of interest was hospital mortality. Secondary outcomes were progression to mechanical ventilation; the prevalence of venous thromboembolism and renal failure; and the change in C-reactive protein, D-dimer, and ferritin levels after tocilizumab administration. Propensity score matching by using a 1:2 protocol was used to match the tocilizumab and non-tocilizumab groups to minimize selection bias. The groups were matched on baseline demographic characteristics, including age, sex, and body mass index; Charlson comorbidity index score; laboratory markers, including ferritin, D-dimer, lactate dehydrogenase, and C-reactive protein values; and the maximum oxygen requirement at the time of tocilizumab administration. Mortality outcomes were evaluated based on the level of oxygen requirement and the day of hospitalization at the time of tocilizumab administration. RESULTS: The overall hospital mortality was significantly reduced in the tocilizumab group when tocilizumab was administered at the nasal cannula level (10.4% vs 22.0%; P = .002). In subjects who received tocilizumab at the nasal cannula level, the progression to mechanical ventilation was reduced versus subjects who were initially on higher levels of oxygen support (6.3% vs 18.7%; P < .001). There was no improvement in mortality when tocilizumab was given at the time of requiring non-rebreather, high-flow nasal cannula, noninvasive ventilator, or invasive ventilator. CONCLUSIONS: Early use of anti-interleukin 6 therapy may be associated with improved hospital mortality and reduction in progression to more severe coronavirus disease 2019.