Critical appraisal of multidrug therapy in the ambulatory management of patients with COVID-19 and hypoxemia. Part I. Evidence supporting the strength of association

Aim: This critical appraisal is focused on three published case series of 119 COVID-19 patients with hypoxemia who were successfully treated in the United States, Zimbabwe, and Nigeria with similar off-label ivermectin-based multidrug treatments that may include ivermectin, nebulized nanosilver, doxycycline, zinc, Vitamins C, and Vitamin D, resulting in rapid recovery of oxygen levels. Methods: We used a simplified self-controlled case series method to investigate the association between treatment and the existence of hospitalization rate reduction. External controls of hospitalized patients were compared against the subgroup of patients with baseline room air SpO2 ≤ 90% to investigate the association between treatment and the existence of mortality rate reduction. Results: No deaths were reported in any of the three case series. One case series reported 5 hospitalization equivalent events (2 ventilations and 3 uses of supplemental oxygen). Combined, the three case series comprised 119 patients of which 61 patients presented with baseline room air SpO2 ≤ 90%. All appropriate external controls were lower-bounded by 12% case fatality rate for hospitalized patients. The existence of hospitalization rate reduction was statistically significant and resilient against both random and systemic selection bias for two out of three case series with the most aggressive treatments. The existence of mortality rate reduction was statistically significant when at least the two case series with the most aggressive treatments were combined. It is more likely than not that random selection bias alone cannot explain this reduction in mortality. Conclusion: These results established an association between the two most aggressive ivermectin-based multidrug treatment protocols and reduction in hospitalization and mortality for hypoxemic COVID-19 patients.