Potential utility of melatonin in deadly infectious diseases related to the overreaction of innate immune response and destructive inflammation: focus on COVID-19

The high mortality of deadly virus infectious diseases including SARS, MERS, COVID-19, and avian flu is often caused by the uncontrolled innate immune response and destructive inflammation.

The majority of viral diseases are self-limiting under the help of the activated adaptive immune system. This activity is cell proliferation dependent and thus, it requires several weeks to develop. Patients are vulnerable and mortality usually occurs during this window period so, to control the innate immune response and reduce the inflammation during this period will increase the tolerance of patients and lowers the mortality in the deadly virus infection.

In this way, many studies have reported the beneficial effects of melatonin on deadly virus infections in different animal models and its therapeutic efficacy in septic shock patients, since it downregulates the overreaction of the innate immune response (causing what is known as a cytokine storm ―a violent immune response with deadly consequences―, and overshooting inflammation), but also promotes the adaptive immune activity.

Melatonin (N-acetyl-5-methoxytryptamine) is a derivative of the essential amino acid tryptophan. In vertebrates, it is only synthesized from tryptophan as a starting material. Limited supply of tryptophan will inevitably result in reduced melatonin production in vertebrates. Fortunately, many foods contain high level of tryptophan including beans, cheese, milk, and turkey meat. Consumption of these food stuffs guarantees the tryptophan supply for melatonin synthesis, provided the enzymatic biosynthesis is not affected. In addition, almost all food stuffs also contain melatonin. These include rice, wheat, corn, fruits, meat, fish, egg, milk, coffee, tea, among others. Consumption of some of these food stuff increases melatonin levels in vertebrates and also in humans. The dual ways of melatonin supply from its endogenous synthesis and extraction from the daily food consumption seem to maintain the persistent melatonin circadian rhythm and levels. This is not always the case as expected. For instance, melatonin levels are significantly reduced with aging in humans and numerous other organisms studied ―something that could be the reason why children under 9 seems to don’t be affected (or less affected) and the infection almost always appears to be mild in older children, whereas older people appear to be more vulnerable to the virus and the consequences of infection are also more severe―. Moreover, other good lifestyle practices related to melatonin production are: not eating too late; not playing sports at night; relaxing two hours before bedtime; dimming the lights; limiting the use of screens at night; and have a fresh and airy bedroom.

Furthermore, since melatonin has a great safety margin without serious adverse effects, authors suggest the use of melatonin as an adjunctive or even regular therapy for deadly viral diseases, especially if no efficient direct anti-viral treatment is available ―although we always recommend to don’t self-medicate and ask your doctor for the correct dosage―. However, melatonin absorption in seriously ill patients would be erratic and difficult to quantify accurately, so, few authors point to the intravenous formulation would be the most recommended, since it would guarantee exact and stable levels, especially in critically ill patients.

Link to the paper: https://doi.org/10.32794/mr11250052

Editorial Disclaimer: information published during the 2020 COVID-19 pandemic may be updated frequently to reflect the dynamic nature of current understanding.

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