Melatonin is the reason why children under the age of 9 seldom exhibit severe symptoms. In fact, children may exhibit mild or even no symptoms at all, even though they have been infected by SARS-CoV-2 [73]. How significant is the difference in melatonin production between children, adults and the elderly?
For most people, peak melatonin production is between the hours of 2 am to 3 am. The maximum melatonin levels measured in healthy adults between the ages of 65 to 70 years appeared to be around 49.3 picograms/ml (pg/ml). Adults more than 75 years of age only have maximum production levels of 27.8 pg/ml [74].
Young children, on the other hand, have extremely high melatonin levels, compared to adults. The maximum levels recorded for children showed a decline as age increased. Children between the ages of 1 to 5 had peak melatonin at 325 pg/ml, while those between the ages of 5 to 11 already declined to 133 pg/ml [76].
Compared to healthy adult seniors, a young child can easily have TEN TIMES the amount of peak melatonin levels. But even then, the actual physiological concentration is extremely low. How much is one picogram, exactly?
To give you some perspective, most melatonin supplements are around 3 to 5 mg per capsule or tablet. One milligram equals 1,000,000,000 picograms. That is why the physiological dosage generally recommended for melatonin supplementation is around 0.3 milligrams [75].
The fact that young children have such high melatonin levels explains why they show very mild symptoms after COVID-19 infections.
Melatonin is a potent inhibitor of NLRP3 inflammasomes.
Generally referred to as the “hormone of darkness”, the ability of melatonin to regulate both pro- as well as anti-inflammatory cytokines in different pathophysiological conditions has only been extensively studied in the past several years.
Controlling cytokine storms is one of the major challenges in the treatment of sepsis [82]. The NLRP3 inflammasome has an interesting nickname of “Pandora’s Box for Sepsis” [83]. Yet nature provides all the solutions to difficult health challenges.
NLRP3 inflammasomes is a direct target of melatonin. Animal models of sepsis showed melatonin’s ability to maintain mitochondrial homeostasis, reduce reactive oxygen species and lower production of proinflammatory cytokines. Melatonin was shown to inhibit NLRP3 inflammasomes in mice with myocardial septic conditions, transforming severe myocardial inflammation into milder symptoms, preventing cardiac failure, and significantly enhanced survival rates of septic mice [77, 78].
An excellent study by Volt et al (2016) showed that chronic low doses of melatonin in aged mice could prevent increase in inflammation, ROS and mitochondria impairments reflective of inflammaging [79, 80]. Volt et al. also showed that acute administration of melatonin could counteract severe inflammatory responses [81].
It is therefore not surprising to find that melatonin is able to prevent ARDS/ALI through suppression of NLRP3 inflammasomes.
In rodent acute lung injury (ALI) models, melatonin was found to markedly reduce pulmonary injury, lower infiltration of macrophages and neutrophils into lungs. Melatonin protected mice from acute lung injuries by inhibiting the activation of NLRP3 inflammasomes through the suppression of extracellular release of histones and blocking histone-induced NLRP3 inflammasome activation [84].
In rodent models of acute respiratory distress syndrome (ARDS), combined treatment of melatonin and mitochondria significantly attenuated progression of ARDS [85].
Melatonin Protects Lung Injury from Mechanical Ventilation Interventions
COVID-19 patients with ARDS/ALI often require intubation with mechanical ventilation. Even though the intervention may help patients, in many instances, patients develop ventilator-induced lung injury as a result of mechanical ventilation [86]. In particular, high ventilation pressures and high tidal volumes required to maintain proper oxygenation and CO2 elimination can cause lung damage and impair gas exchange.
A study released on March 6, 2020 by Geng-Chin Wu et al. demonstrated that by increasing melatonin with the use of a melatonin receptor agonist, damaging effects of ventilator-induced lung injury could be prevented in rodent models [87].
The full therapeutic potential of melatonin in its ability to modulate the immune system, especially the critical function of suppressing cytokine storms to prevent progression of acute respiratory distress syndrome (ARDS) and respiratory failure in infected patients was clearly demonstrated in a study by Huan]g et al. (2019). Huang et al. infected rodents with the highly lethal and infectious H1N1 influenza A virus. Co-treatment of these infected rodents with melatonin and an antiviral drug significantly increased their survival rates compared to mice treated only with antivirals alone [88]!
It is no wonder that none of the pregnant mothers infected by COVID-19 admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, developed severe pneumonia or died; nor were their babies infected by COVID-19 [89]. Why?
Melatonin secretion in the third trimester of pregnancy is more than doubled compared to the first trimester.
COVID-19, Pneumonia & Inflammasomes – The Melatonin Connection
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