The coronavirus illness 2019 (COVID-19), caused by SARS-CoV-2, is a global health hazard. The recent detection of SARS-CoV-2 in the cerebrospinal fluid (CSF) and in frontal lobe sections from postmortem examination has confirmed the presence of the virus in neural tissue. This finding reveals a new direction in the search for a neurotherapeutic strategy in the COVID-19 patients with underlying diseases. It is important to consider the COVID-19 outbreak in a neuroinvasiveness context and the therapeutic use of high doses of melatonin, which may favorably modulate the immune response and neuroinflammation caused by SARS-CoV-2.