Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity score-matched Retrospective Cohort Study
Propensity matched retrospective prophylaxis study of healthcare workers in the Dominican Republic showing significantly lower cases with treatment, and no hospitalization with treatment (versus 2 in the PSM matched control group). The cases with treatment were mostly in the first week, with only one case in the second and third weeks, and none in the fourth week. There were no severe side effects. In post-hoc analysis, as the treatment group discontinued treatment over time, their protection also decreased. NCT04832945.
risk of hospitalization, 80.0% lower, RR 0.20, p = 0.50, treatment 0 of 271 (0.0%), control 2 of 271 (0.7%), continuity correction due to zero event, PSM. risk of COVID-19 case, 74.0% lower, RR 0.26, p = 0.008, treatment 5 of 271 (1.8%), control 18 of 271 (6.6%), adjusted, PSM, multivariate Cox regression.
Morgenstern et al., 4/16/2021, retrospective, propensity score matching, Dominican Republic, Caribbean, peer-reviewed, 16 authors, dosage 200μg/kg weekly.
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C.
The ivermectin dosage was low for 42 days prophylaxis - only a single dose of 200µg/kg, with a maximum of 12mg.
Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters.
There were no hospitalizations and no deaths. NCT04446104.
Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022.
Findings
All patients recruited completed the trial (median age, 26 [IQR 19–36 in the ivermectin and 21–44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77–1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001).
Interpretation
Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials.
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