• Early treatment shows 65% [54‑74%] lower risk with pooled effects in 38 studies. Results are similar for higher quality studies and for peer-reviewed studies. The 16 mortality and 16 hospitalization results show 76% [60‑86%] lower mortality and 41% [28‑51%] lower hospitalization.
• Late treatment is less successful, with 20% [16‑24%] lower risk from 267 studies. Very late treatment may be harmful, especially with excessive dosages.
• Randomized Controlled Trials show 17% [4‑29%] lower risk, or 23% [9‑36%] when excluding late treatment.
• There is substantial bias towards publishing negative results. Prospective studies show higher efficacy. Negative RCTs received priority treatment at top journals, while positive trials report difficulty publishing. There is a strong geographical bias, with significantly more negative studies from North America.
• Results are missing for 54% of early treatment and prophylaxis RCTs, compared to 18% for late treatment, consistent with the higher prevalence of positive studies for early treatment and prophylaxis, and bias against publishing positive results.
• No treatment or intervention is 100% effective. All practical, effective, and safe means should be used based on risk/benefit analysis. Multiple treatments are typically used in combination, which may be significantly more effective. Lung pharmacokinetics show high inter-individual variability Ruiz.
• All data to reproduce this paper and the sources are in the appendix. Multiple other meta analyses show efficacy for early treatment or prophylaxis García-Albéniz, Ladapo, Landsteiner de Sampaio Amêndola, Prodromos, Risch, Risch (B), Stricker.
