Background We systematically assessed benefits and harms of the use of ivermectin (IVM) in COVID-19 patients. Methods Published and preprint randomized controlled trials (RCTs) assessing IVM effects on COVID-19 adult patients were searched until March 22, 2021 in five engines. Primary outcomes were all-cause mortality, length of stay (LOS), and adverse events (AE). Secondary outcomes included viral clearance and severe AEs. Risk of bias (RoB) was evaluated using Cochrane RoB 2·0 tool. Inverse variance random effect meta-analyses were performed. with quality of evidence (QoE) evaluated using GRADE methodology. Results Ten RCTs (n=1173) were included. Controls were standard of care [SOC] in five RCTs and placebo in five RCTs. COVID-19 disease severity was mild in 8 RCTs, moderate in one RCT, and mild and moderate in one RCT. IVM did not reduce all-cause mortality vs. controls (RR 0.37, 95%CI 0.12 to 1.13, very low QoE) or LOS vs. controls (MD 0.72 days, 95%CI −0.86 to 2.29, very low QoE). AEs, severe AE and viral clearance were similar between IVM and controls (all outcomes: low QoE). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality in three RCTs at high RoB was reduced with IVM. Conclusions In comparison to SOC or placebo, IVM did not reduce all-cause mortality, length of stay or viral clearance in RCTs in COVID-19 patients with mostly mild disease. IVM did not have an effect on AEs or severe AEs. IVM is not a viable option to treat COVID-19 patients.

Objetivos: Realizar una revisión sistemática acerca de la efectividad y seguridad del uso de dióxido de cloro y derivados del cloro, en la prevención o el tratamiento de la COVID-19. Materiales y métodos: Se siguieron las pautas internacionales de elaboración de revisiones sistemáticas de PRISMA y el Manual Cochrane para revisiones sistemáticas de intervenciones. La estrategia de búsqueda la desarrolló un bibliotecario y la revisaron dos de los autores. Se complementó la búsqueda electrónica con una búsqueda manual. Se incluyeron ensayos clínicos aleatorizados, estudios cuasiexperimentales, estudios de cohorte, estudios de casos y controles, estudios de corte transversal y reportes de casos; y se excluyeron estudios in vitro o realizados en animales. Dos revisores, de forma independiente, seleccionaron los estudios según los criterios de elegibilidad definidos, usando el aplicativo web Rayyan, en caso de discordancia se hizo partícipe a un tercer revisor. El protocolo de la revisión sistemática se registró en PROSPERO (CRD42020200641). Resultados: No se identificó ningún estudio publicado ni en proceso de publicación que haya evaluado el uso del dióxido de cloro o derivados del cloro, administrado por vía inhalatoria, oral o parenteral en humanos, como agente preventivo o terapéutico de la COVID-19 o en infecciones por otros coronavirus. Solo se identificó el registro de un único estudio catalogado como observacional que hasta ahora no tiene resultados. Conclusiones: A la fecha, no existe evidencia científica que apoye el uso del dióxido de cloro o derivados del cloro para prevenir o tratar la COVID-19.

Background: We systematically assessed benefits and harms of the use of ivermectin (IVM) in COVID-19 patients. Methods: Published and preprint randomized controlled trials (RCTs) assessing IVM effects on COVID-19 adult patients were searched until March 15, 2021 in five engines. Primary outcomes were all-cause mortality, length of stay (LOS), and adverse events (AE). Secondary outcomes included viral clearance and severe AEs. We evaluated risk of bias (RoB) using the Cochrane RoB 2.0 tool. Inverse variance random effect meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. Subgroup analyses by severity of disease and RoB, and sensitivity analyses by time of follow-up were conducted. Results: Ten RCTs (n=1173) were included. Controls were standard of care [SOC] in five RCTs and placebo in five RCTs. RCTs sample size ranged from 24 to 398 patients, mean age from 26 to 56 years-old, and severity of COVID-19 disease was mild in 8 RCTs, moderate in one RCT, and mild and moderate in one RCT. IVM did not reduce all-cause mortality vs. controls (RR 1.11, 95%CI 0.16-7.65, very low QoE). IVM did not reduce LOS vs. controls (MD 0.72 days, 95%CI -0.86 to 2.29, very low QoE). AEs, severe AE and viral clearance were similar between IVM and controls (low QoE for these three outcomes). Subgroup analyses by severity of COVID-19 disease or RoB were consistent with main analyses. Sensitivity analyses excluding RCTs with follow up <21 days showed no difference in all-cause mortality but diminished heterogeneity (I2=0%). Conclusions: In comparison to SOC or placebo, IVM did not reduce all-cause mortality, length of stay or viral clearance in RCTs in COVID-19 patients with mostly mild disease. IVM did not have effect on AEs or SAEs. IVM is not a viable option to treat COVID-19 patients.