COVID-19: Melatonin as a potential adjuvant treatment

There are researches showing that melatonin has positive effects in alleviating acute respiratory stress induced by virus, bacteria, radiation, etc. This paper reviews evidence indicating melatonin also helps relieve COVID-19 induced pneumonia, acute lung injury and acute respiratory distress syndrome.
SARS-CoV-2 infected patients show symptoms of fever, dry cough, myalgia, fatigue, and diarrhea, etc. Examination of infected lung shows edema, proteinaceous exudate with globules, patchy inflammatory cellular infiltration and moderate formation of hyaline membranes. From genetic point of view, SARS-CoV-2 shares 79.0% nucleotide identity to SARS-CoV and 51.8% identity to MERS-CoV. COVID-19 resembles MERS genetically and pathologically. Therefore, researchers predict an increase in a cytokine and decrease in immune function in COVID-19 patients.
Melatonin is not viricidal, but it can indirectly act against virus due to its anti-inflammation, anti-oxidation and immune enhancing function. Melatonin can down-regulate macrophage polarization and NF-κB activation in T cells and lung tissue, contributing to its anti-inflammation function.
The anti-oxidative effect of melatonin works by up-regulating anti-oxidative enzymes, down-regulating pro-oxidative enzymes, and potentially interacting directly with free radicals as free radical scavenger.
It has been shown that patients with COVID-19 have reduced level of neutrophils, lymphocytes and CD8+ T cells in peripheral blood. Melatonin regulates immune response by improving proliferation and maturation of natural killing cells, T and B lymphocytes, granulocytes and monocytes in both bone marrow and other tissues. What’s more, NLRP3 is correlated with lung infection and has balance of protective and damaging actions in lungs. It is proven that in radiation-induced lung injury, melatonin can reduce the infiltration of macrophages and neutrophils into the lung in ALI due to the inhibition of NLRP3 inflammasome.
Safety of melatonin has been verified in many human studies. When given to COVID-19 patients, they still need to be carefully monitored.
The anti-inflammation, anti-oxidation and immune response regulation effect make melatonin a potential candidate as adjuvant therapy for patients with COVID-19. Melatonin has a high safety profile. Although the direct evidence of melatonin application in COVID-19 is unclear, both its use in experimental animal models and studies on humans have shown promising results. The author concludes that using melatonin in patients with COVID-19 would be beneficial.

Link to paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102583/

Reference:
Zhang, Rui et al. “COVID-19: Melatonin As A Potential Adjuvant Treatment”. Life Sciences, vol 250, 2020, p. 117583. Elsevier BV, doi:10.1016/j.lfs.2020.117583.
Palash. “Melatonin as a potential therapeutic molecule against COVID-19 associated gastrointestinal complications: An unrevealed link”. Melatonin-Research.Net, 2020, https://www.melatonin-research.net/index.php/MR/article/view/89/571.