Abstract: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Ivermectin for COVID-19 in Peru: 14-fold reduction in nationwide excess deaths, p < 0.002 for effect by state, then 13-fold increase after ivermectin use restricted Juan J. Chamie-Quintero, a Jennifer A. Hibberd, b David E Scheim c Lead author: Juan J. Chamie, Independent data analyst, Cambridge, MA (USA) email: jchamieq@eafit.edu.co Jennifer A. Hibberd Jennifer A. Hibberd, DDS, MRCDC (email: drjenniferhibberd@gmail.com) William Osler Health System; Trillium Health Partners Hospital Centres; Instructor at the University of Toronto, Canada Corresponding author: David E. Scheim, PhD, US Public Health Service, Commissioned Corps, Inactive Reserve 2516 Ridge Road, Blacksburg, VA 24060 (USA). Phone 540 320-8013. Fax 540 552-8014. MeSH terms: COVID-19; ivermectin; Spike Protein, Coronavirus Juan J. Chamie-Quintero (email: jchamieq@eafit.edu.co ) is a data analyst in Cambridge, MA, USA. Jennifer A. Hibberd, DDS, MRCDC (email: drjenniferhibberd@gmail.com) is a specialist dental surgeon at William Osler Health System and Trillium Health Partners Hospital Centres and an instructor at University of Toronto. c David E. Scheim, PhD (email: dscheim@alum.mit.edu) is a commissioned officer in the US Public Health Service, inactive reserve. Page 1 of 15 a b 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 ABSTRACT Objective. We aimed to identify mortality trends associated with COVID-19 deaths in Peru during April through November 2020, when mass treatments with ivermectin (IVM), a drug of Nobel Prize-honored distinction, were autonomously deployed at different times and to different extents in Peru’s 25 states under a national policy that authorized these treatments. Design. Ecological study of publicly available data. Excess deaths were analyzed state by state. To identify potential confounding factors, Google mobility data, population densities, SARS-CoV2 genetic variations, seropositivity rates and other auxiliary data were also examined. Primary outcome. Reductions in excess deaths, state by state, as compared with extent and time period of IVM treatments. Participants. The study population was restricted to ages ≥ 60 to eliminate confounding effects of changing age distributions of COVID-19 incidence. Results. The 25 states of Peru were grouped by extent of IVM distributions: maximal (mass IVM distributions through operation MOT, a broadside effort led by the army); medium (locally managed IVM distributions); and minimal (restrictive policies in one state, Lima). The mean reduction in excess deaths 30 days after peak deaths was 74% for the maximal IVM distribution group, 53% for the medium group and 25% for Lima. Reduction of excess deaths correlated with extent of IVM distribution by state with p<0.002 using the Kendall τb test. Nationwide, excess deaths decreased 14-fold over four months through December 1, 2020, after which deaths then increased 13-fold when IVM use was restricted under a new president. Conclusion. Mass treatments with IVM, a drug safely used in 3.7 billion doses worldwide since 1987, most likely caused these reductions in deaths during the time periods in which it was deployed. The indicated biological mechanism of IVM, competitive binding with SARS-CoV-2 spike protein, is likely non-epitope specific, possibly yielding full efficacy against emerging viral mutant strains. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 STRENGTHS AND LIMITATIONS OF THIS..