Background The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. Methods We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. Results We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P=0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P=0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P=0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. Conclusions Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937 .)
This review summarizes current knowledge about the transmission of SARS-CoV-2. Evidence-based policies and practices should incorporate the accumulating knowledge regarding SARS-CoV-2 transmission to help educate the public and slow spread of this virus.
Background and Aims Coronavirus disease 2019 (COVID‐19) leads to elevated liver biochemistries in approximately half of patients on presentation. To date, data are limited regarding the trend of liver biochemistries over the course of illness. We aimed to evaluate the trend, etiology, and outcomes associated with liver biochemistries in COVID‐19. Approach and Results A total of 60 patients with COVID‐19 were admitted between March 21 and March 28, 2020. The mean age was 57 years, 65% were male, and 28% were Hispanic. At the study conclusion, 6 patients were deceased, 28 were discharged, and 26 remained admitted. Patients who remained admitted were followed for a median of 12 days. Of 60 patients, 41 (69%) had at least one abnormal liver biochemistry on admission. Median aspartate aminotransferase (AST) was higher than alanine aminotransferase (ALT) at admission (46 vs. 30 U/L) and during the hospital course. Aminotransferases rose above normal in 54 (93%) patients, whereas alkaline phosphatase and total bilirubin elevations were rare. Ten (17%) patients developed aminotransferases more than 5 times the upper limit of normal. AST highly correlated with ALT throughout the illness course (r = 0.97; P < 0.0001), whereas correlations with markers of muscle injury and inflammation were weak. Statin use was common before (40%) and during admission (80%) at our center, with no difference in peak liver biochemistries between users and nonusers. No demographic or comorbid illness was associated with liver injury. Admission AST (69 vs. 49; P < 0.05), peak AST (364 vs. 77; P = 0.003), and peak ALT (220 vs. 52; P = 0.002) were higher in intubated patients. Conclusions AST‐dominant aminotransferase elevation is common in COVID‐19, mirrors disease severity, and appears to reflect true hepatic injury.
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