Background: Ivermectin has demonstrated different mechanisms of actions that could potentially protect from both COVID-19 infection and COVID-19-related comorbidities. Based on the existing literature and safety profile of ivermectin, a citywide program of prophylactic use of ivermectin for COVID-19 was implemented in Itajai, a Southern city in Brazil in the state of Santa Catarina. The objective of this analysis is to evaluate the effects of the use of ivermectin for prevention of COVID-19 infection, risk of dying and mortality, compared to non-users. Materials and methods: This is a retrospective analysis of registry data from the medical based citywide COVID-19 prevention with ivermectin program, between July 2020 to December of 2020. The whole population of Itajaí was invited for a medical visit to compile demographic and medical parameters. In the absence of contraindications, ivermectin was offered as an optional treatment for 2 days every 15 days at a dose of 0.2mg/kg/day. Patients’ preferences and medical autonomy were preserved. Ivermectin users were compared with the comorbidity-matched population of non-users for COVID-19 by age, sex, COVID-19 infection rate, and COVID-19 mortality rate. Results in terms of mortality were adjusted for all relevant variables and Propensity Score Matching (PSM) was calculated. Results: A total of 220,517 subjects were included in the analysis; 133,051 (60.3%) ivermectin users and 87,466 (39.7%) non-users. COVID-19 infection occurred in 4,311 (3.2%) treated subjects, and 3,034 (3.5%) non-treated subjects.

This evidence showed a 7% reduction in COVID-19 infection rate with use of ivermectin: COVID-19 infection rate ratio (Risk ratio (RR) of 0.93; 95% confidence interval (CI), 0.89 – 0.98; p = 0.003). A total of 62 deaths (1.4% mortality rate) occurred among users and 79 deaths (2.6% mortality rate) among non-users, showing a 48% reduction in mortality rate (RR, 0,52; 95%CI, 0.37 – 0.72; p = 0.0001). Risk of dying from COVID-19 among ivermectin users was 45% lower than non-users (RR, 0.55; 95%CI, 0.40 – 0.77; p = 0.0004).

Conclusion: Prophylactic use of ivermectin showed significantly reduced COVID-19 infection rate, mortality rate and chance of dying from COVID-19 on a calculated population-level analysis, which controlled for all relevant confounding variables.

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