The Role of Melatonin in COVID-19 Treatment and in Neurocognitive Health - Commentary and Call to Action

A vast evidentiary base of research with both observational and clinical trials supports that the pineal hormone melatonin, a powerful immunomodulator as studies have clarified, whose primary function is the regulation of the sleep-wake cycle, possesses an extraordinarily wide spectrum of anti-inflammatory, antioxidant, and antiapoptotic activity, with potential cytoprotective, neuroprotective, nephroprotective, cardioprotective, anti-hypertensive, anti-nociceptive, and antiviral effects, and with emerging evidence of benefit in neurocognitive disorders (especially but solely Alzheimer’s disease (AD)). In this commentary and short review, we explore the frontier edge of the emerging potential role of the chronobiotic agent melatonin, in both the treatment of SARS-2-CoV infection (COVID-19 disease), and its emerging role in neurocognitive health. Given the recognized dysregulated neuro-inflammatory processes that underlie SARS-CoV-2 infection, there is motivation for exploring melatonin’s deployment in the potential amelioration of some of the newly identified pathological neurocognitive sequelae, notably the cognitive impairment that is increasingly exhibited as part of the cluster known as post-acute sequelae of COVID-19 (PASC), aka “Long COVID”. In the process we review clinical evidence of benefit in these domains, suggesting the strong promise that melatonin appears to provide, with a highly favorable benefit/harm ratio of excellent tolerability, minimal toxicity, affordability, self-administrable, and sufficiently compelling evidence of efficacy as to be actionable, in the here and now. We conclude with a call to action to encourage and nurture further research in melatonin’s continually expanding range of benefits, and to support its informed deployment within the current treatment landscape.