Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019

Abstract

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.

Therapeutic potential of ivermectin as add on treatment in COVID 19: A systematic review and meta-analysis

“…It is important to note that at the time of analysis, 2 of the included studies were not peer-reviewed and were retrieved from the preprint server. However, one of these, the ICON study by Rajter et al has been recently published (18). To the best of our knowledge, this is the first systematic review and meta-analysis on the effectiveness of add-on ivermectin in COVID-19 patients.…”

“…Based on this, researchers have proposed the use of ivermectin as an add on therapy for COVID-19 treatment (16). Few observational studies have been performed to evaluate the effectiveness of ivermectin in the treatment of COVID-19 and have shown favourable result (17)(18)(19)(20). However, there is a wide disparity regarding the clinical benefit accrued from this drug.…”

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial

“…As of December 21, 2020, there are 45 studies evaluating the efficacy of ivermectin to treat or prevent COVID-19 registered in clinicaltrials.gov, and 74 trials registered in WHO´s International Clinical Trials Registry Platform ( https://apps.who.int/trialsearch/ ) of which at least 14 are already completed. Although some observational and case control studies as well as emerging small randomized clinical trials suggest a potential utility [10] , [11] , [12] , [13] . Yet, there is still a dearth of robust, randomized controlled trials to appropriately inform policy decisions.…”

Unraveling the mechanism of arbidol binding and inhibition of SARS-CoV-2: Insights from atomistic simulations

“…However, another human trial showed that the drug did not help patients in China with severe COVID-19 ( Wang et al, 2020d ). Several clinical trials are also underway to evaluate the suitability and efficacy of other antiviral drugs, such as favipiravir, darunavir, ribavirin, galidesivir, oseltamivir, arbidol, etc., for treating COVID-19 ( De Clercq, 2004 ; Dong et al, 2020 ; Elfiky, 2020 ; Koren et al, 2003 ; Li et al, 2020 ; Rajter et al, 2020 ; Runfeng et al, 2020 ; Sarzi-Puttini et al, 2020 ; Tu et al, 2020 ; Velavan and Meyer, 2020 ; Wang et al, 2020a ; Wu and Yang, 2020 ).…”