Abstract: Original Manuscript 20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment Journal of Evidence-Based Integrative Medicine Volume 26: 1-13 ª The Author(s) 2021 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/2515690X211026193 journals.sagepub.com/home/cam Leon Margolin, MD, PhD1 , Jeremy Luchins, PhD1 , Daniel Margolin, Bsc1, Michelle Margolin1, and Sanford Lefkowitz, MSc1 Abstract Objectives and Setting. As the lethal COVID-19 pandemic enters its second year, the need for effective modalities of alleviation remains urgent. This includes modalities that can readily be used by the public to reduce disease spread and severity. Such preventive measures and early-stage treatments may temper the immediacy of demand for advanced anti-COVID measures (drugs, antibodies, vaccines) and help relieve strain also on other health system resources. Design and Participants. We present results of a clinical study with a multi-component OTC “core formulation” regimen used in a multiply exposed adult population. Analysis of clinical outcome data from our sample of over 100 subjects  comprised of roughly equal sized regimen-compliant (test) and non-compliant (control) groups meeting equivalent inclusion criteria  demonstrates a strong statistical significance in favor of use of the core formulations. Results. While both groups were moderate in size, the difference between them in outcomes over the 20-week study period was large and stark: Just under 4% of the compliant test group presented flu-like symptoms, but none of the test group was COVID-positive; whereas 20% of the non-compliant control group presented flu-like symptoms, three-quarters of whom (15% overall of the control group) were COVID-positive. Conclusions. Offering a low cost, readily implemented anti-viral approach, the study regimen may serve, at the least, as a stopgap modality and, perhaps, as a useful tool in combatting the pandemic. Keywords COVID-19, SARS-CoV-2, prophylaxis, early-stage treatment, OTC, zinc, ionophores, immunity enhancement, regimen compliance Received March 11, 2021. Received revised May 04, 2021. Accepted for publication May 30, 2021.