Highlights
- •Ivermectin, an FDA-approved anti-parasitic agent, was found to be an inhibitor of SARS-CoV-2 replication in the laboratory.
- •Ivermectin may be effective for the treatment of early-onset mild COVID-19 in adult patients.
- •Early viral clearance of SARS-CoV-2 was observe in ivermectin-treated patients.
- •Remission of fever, cough, and sore throat did not differ among treatment groups. No severe adverse event was observed.
- •Larger trials will be needed to confirm these preliminary findings.
Abstract
Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.
Introduction
Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic of the highest priority (Johns Hopkins University of Medicine, 2020). Eighty-one percent of cases are categorized as mild, for whom symptomatic management at home and monitoring of clinical deterioration is recommended (Centers for Disease Control and Prevention, 2020). Despite providing symptomatic management, a therapeutic drug that would limit the course of infection is greatly needed. Ivermectin, a popular anti-parasitic drug, acts on SARS-CoV-2 by preventing viral proteins from entering the host cell nucleus (Caly et al., 2020). Recent virtual drug screening identified doxycycline as a potential inhibitor of SARS-CoV-2 papain-like protease (Wu et al., 2020). An observational study in which patients were treated with a single dose of ivermectin and multiple doses of doxycycline for the treatment of COVID-19 yielded considerable improvements in symptoms and the viral response (Alam et al., 2020). A recent retrospective study found that hospitalized patients given ivermectin with other treatments (e.g., azithromycin and hydroxychloroquine) had lower mortality than those who did not receive ivermectin (Rajter et al., 2020). Further studies are needed to verify these findings. This need is further underscored by the observation that SARS-CoV-2 multiplies rapidly in the respiratory tract and that evidence from animal models shows three-fold higher levels of ivermectin in pulmonary tissue than in the plasma at 1 week after oral dosing (Chiu and Lu, 1989; Lespine et al., 2005). This pilot study was performed to evaluate the rapidity of viral clearance and safety of a 5-day course of ivermectin or a single-dose of ivermectin + a 5-day course of doxycycline in the treatment of mild COVID-19 in adults.