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Initial pathology is due to the virus binding to the ACE\u20102 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28\u00a0days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and\/or taste, fatigue, cough, aching pain, \u201cbrain fog,\u201d insomnia, shortness of breath, and tachycardia) after 12\u00a0weeks and are diagnosed with a syndrome named \u201cLONG COVID.\u201d Longitudinal clinical studies in a group of subjects who were infected with SARS\u2010CoV\u20102 have been compared to a non\u2010infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self\u2010report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively. It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid\u2010derived 2\u2010like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re\u2010purposing studies in \u201cLONG COVID\u201d subjects experiencing insomnia, depression, fatigue, and \u201cbrain fog\u201d but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.<\/jats:p>","DOI":"10.1002\/prp2.911","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T03:08:36Z","timestamp":1642129716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["\u201cLONG COVID\u201d\u2014A hypothesis for understanding the biological basis and pharmacological treatment strategy"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2379-0493","authenticated-orcid":false,"given":"Bevyn","family":"Jarrott","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience &amp; Mental Health University of Melbourne  Parkville Victoria 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