Background Ivermectin was shown to inhibit SARS-CoV-2 replication in-vitro, which has led to off-label use, but clinical efficacy has not been previously described. Research Question Does ivermectin benefit hospitalized COVID-19 patients? Study Design and Methods: Charts of consecutive patients hospitalized at four Broward Health hospitals in Florida with confirmed COVID-19 between March 15 through May 11, 2020 treated with or without ivermectin were reviewed. Hospital ivermectin dosing guidelines were provided but treatment decisions were per treating physician’s discretion. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included mortality in patients with severe pulmonary involvement, extubation rates for mechanically ventilated patients, and length of stay. Severe pulmonary involvement was defined as need for FiO 2 ≥50%, noninvasive ventilation, or invasive ventilation at study entry. Logistic regression and propensity score matching were used to adjust for confounders. Results 280 patients, 173 treated with ivermectin and 107 without ivermectin, were reviewed. Most patients in both groups also received hydroxychloroquine and/or azithromycin. Univariate analysis showed lower mortality in the ivermectin group (15.0% versus 25.2%, OR 0.52, CI 0.29-0.96, P=0.03). Mortality was also lower among ivermectin-treated patients with severe pulmonary involvement (38.8% vs 80.7%, OR 0.15, CI 0.05-0.47, p=0.001). There were no significant differences in extubation rates (36.1% vs 15.4%, OR 3.11 (0.88-11.00), p=0.07) or length of stay. After multivariate adjustment for confounders and mortality risks, the mortality difference remained significant (OR 0.27, CI 0.09-0.80, p=0.03). 196 patients were included in the propensity-matched cohort. Mortality was significantly lower in the ivermectin group (13.3% vs 24.5%, OR 0.47, CI 0.22-0.99, p<0.05); an 11.2% (CI 0.38%-22.1%) absolute risk reduction, with a number needed to treat of 8.9 (CI 4.5-263). Interpretation Ivermectin treatment was associated with lower mortality during treatment of COVID-19, especially in patients with severe pulmonary involvement. Randomized controlled trials are needed to confirm these findings.

Importance: No therapy to date has been shown to improve survival for patients infected with SARS-CoV-2. Ivermectin has been shown to inhibit the replication of SARS-CoV-2 in vitro but clinical response has not been previously evaluated. Objective: To determine whether Ivermectin is associated with lower mortality rate in patients hospitalized with COVID-19. Design and Setting: Retrospective cohort study of consecutive patients hospitalized at four Broward Health hospitals in South Florida with confirmed SARS-CoV-2. Enrollment dates were March 15, 2020 through May 11, 2020. Follow up data for all outcomes was May 19, 2020. Participants: 280 patients with confirmed SARS-CoV-2 infection (mean age 59.6 years [standard deviation 17.9], 45.4% female), of whom 173 were treated with ivermectin and 107 were usual care were reviewed. 27 identified patients were not reviewed due to multiple admissions, lack of confirmed COVID results during hospitalization, age less than 18, pregnancy, or incarceration. Exposure: Patients were categorized into two treatment groups based on whether they received at least one dose of ivermectin at any time during the hospitalization. Treatment decisions were at the discretion of the treating physicians. Severe pulmonary involvement at study entry was characterized as need for either FiO2 ≥50%, or noninvasive or invasive mechanical ventilation. Main Outcomes and Measures: The primary outcome was all-cause in-hospital mortality. Secondary outcomes included subgroup mortality in patients with severe pulmonary involvement and extubation rates for patients requiring invasive ventilation. Results: Univariate analysis showed lower mortality in the ivermectin group (25.2% versus 15.0%, OR 0.52, 95% CI 0.29-0.96, P=.03). Mortality was also lower among 75 patients with severe pulmonary disease treated with ivermectin (38.8% vs 80.7%, OR 0.15, CI 0.05-0.47, P=.001), but there was no significant difference in successful extubation rates (36.1% vs 15.4%, OR 3.11 (0.88-11.00), p=.07). After adjustment for between-group differences and mortality risks, the mortality difference remained significant for the entire cohort (OR 0.27, CI 0.09-0.85, p=.03; HR 0.37, CI 0.19-0.71, p=.03). Conclusions and Relevance: Ivermectin was associated with lower mortality during treatment of COVID-19, especially in patients who required higher inspired oxygen or ventilatory support. These findings should be further evaluated with randomized controlled trials.

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