Can Melatonin Reduce the Severity of COVID-19 Pandemic?

Abstract

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing lifethreatening danger to the elderly and people with diseases of chronic inflammation. So, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children do not suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats also do not suffer from the virus they transmit, and bats too have a much higher level of melatonin. Viruses generate an explosion of reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. Melatonin inhibits the programmed cell death which coronaviruses induce, causing significant lung damage. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks the inflammasome. The immune response is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the negative effects of coronavirus infection on patients' health after the active phase of the infection is over.

A systematic review of COVID-19 and obstructive sleep apnoea

“…Recent studies have suggested that the sleep hormone melatonin may be beneficial for the treatment of COVID-19 [ [28] , [29] , [30] ]. Melatonin may decrease oxidative stress, inflammation and the immune response, which may be particularly important in patients with OSA in whom these pathways are already activated.…”

“…There are a number of plausible pathways by which COVID-19 might have an adverse effect on OSA patients and further research is warranted to investigate these pathways. Furthermore, given that recent studies suggest that melatonin may be beneficial for the treatment of COVID-19 [ [28] , [29] , [30] ] it remains to be seen if sleep and treatment for sleep disorders may have beneficial effects on COVID-19 outcomes.…”

Immune response to COVID-19 infection: a double-edged sword

“…Inflammation is placed on the first line of innate immunity defense. Today, the recent studies had unequivocally confirmed that COVID-19 severity was positively correlated with the degree of inflammation [17][18][19][20][21]. Zhang et al [22] found that severe COVID-19 patients had had a hyper inflammation signature compared to non-severe cases.…”

“…Once present in the host cell, the SarS-CoV-2 activates the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. This contributes to the release of the pro-inflammatory cytokines, interleukin (IL)-1b and IL-18 [20]. The downstream NF-jB pathway was also activated upon the interaction of the viral RNA with toll-like receptor (TLR) 3, TLR7, TLR8, and TLR9, which enhances pro-inflammatory cytokines production too.…”

The Circadian Clock and Viral Infections

“…In mouse model systems, melatonin can inhibit the NLRP3 inflammasome (Y. Zhang et al, 2016; Cao et al, 2017; Ma et al, 2018), leading us and others (Shneider et al, 2020) to speculate a role for this inflammatory pathway in COVID-19.…”