After starting in late 2019, COVID-19 spread worldwide, and Italy was one of the first Western nations to be seriously affected. At that time, both the virus and the disease were little known and there were no Evidence-Based Medicine indications for treatment. The Italian Health Ministry guidelines claimed that, unless oxygen saturation fell to <92%, no pharmacological treatment was necessary during the first 72 hours, other than on a purely symptomatic basis, preferably with paracetamol. As later confirmed, that delay in therapeutic intervention may have been responsible for numerous hospital admissions and a very high lethality (3.5 %). To try to remedy this situation, several volunteer groups were formed, managing to promptly cure thousands of patients at home with non-steroidal anti-inflammatory drugs and a variety of re-purposed drugs (principally hydroxychloroquine, ivermectin) and supplements (such as antioxidants, polyphenols and vitamin D). Although not documented by any randomized controlled studies, these approaches were nonetheless based on the best available evidence, were aimed at addressing otherwise unmet major needs and produced a significant reduction of hospitalizations, of symptom duration, and a complete recovery from the disease compared with late treatment, according to some retrospective observational studies and the clinical experience of many physicians. A prompt discussion, with a clear and open exchange between healthcare Institutions and the said groups of voluntary physicians, could clarify the most effective approaches to reduce the number of hospitalizations and the lethality of this disease.