Study: Possible application of melatonin in prolonged COVID. Image credit: metamorworks / Shutterstock
Record
An emerging concern related to the coronavirus disease 2019 (COVID-19) pandemic is long-term COVID or clinical sequelae consisting of chronic fatigue, memory loss, muscle weakness, reduced lung capacity during exercise, persistent fever, myalgia , seizures, stroke and other cardiovascular complications. Patients who have recovered from severe COVID-19 experience these debilitating symptoms for months after recovery. In addition, studies examining vaccinated individuals who experienced breakthrough SARS-CoV-2 infections with severe acute respiratory syndrome found a high incidence of long-term COVID symptoms, such as worsening musculoskeletal, neurological, and mental health among these individuals. after recovery. This suggests that vaccination provides only limited protection against long-term COVID. Melatonin is a cryoprotective hormone and chemical that exhibits anti-inflammatory, antioxidant, and immunomodulatory effects and has been shown to impair viral infections, play a role in maintaining circadian rhythms, and is effective against diabetes mellitus and cardiovascular disease. It also participates in the activation of the enzymes that synthesize glutathione. Melatonin could potentially be a therapeutic agent for treating long-term symptoms of COVID.
Consequences of SARS-CoV-2 central nervous system infection. ACE2: angiotensin-converting enzyme 2. BBB: blood-brain barrier.
Long COVID symptoms
Brain fog is a general term used to define impaired cognitive function, such as difficulty concentrating, loss of working and short-term memory, and difficulty with verbal and non-verbal methods of learning and mathematical problem solving. While brain fog can be a consequence of various factors such as sleep deprivation, malnutrition, hormonal changes associated with pregnancy or menopause, or even chemotherapy, it was the most commonly reported symptom among patients recovering from COVID-19 without history of other diseases or hypoxia. . An intelligence test in the UK has identified cognitive impairment in a significant number of people with COVID-19. Symptoms included memory loss, disorientation and reduced mental energy. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by excessive and persistent fatigue, inability to exercise, and autonomic dysregulation. ME/CFS is also associated with disruption of circadian rhythms and gut/mucosa barrier, mitochondrial dysfunction and pro-inflammatory state. Studies have shown that 45% of COVID-19 patients who were hospitalized and required admission to the intensive care unit experienced ME/CFS symptoms up to six months after recovery.
Melatonin as a potential long-term treatment for COVID
Melatonin is a hormone produced naturally in all aerobically respiring life forms and performs antioxidant, anti-inflammatory, immunostimulatory and neuroprotective functions in the body. It reduces the proinflammatory response of macrophages, activates nuclear erythroid-related factor 2, and suppresses nuclear factor (NF)-κB activation. Melatonin is also known to balance inflammatory responses by reducing the levels of pro-inflammatory cytokines such as interleukins (IL) 1β, 6 and 8 and tumor necrosis factor (TNF)-α and increasing the anti-inflammatory cytokine IL-10. The Warburg effect during viral infections causes a shift from mitochondrial oxidative phosphorylation to glycolysis occurring in the cytoplasm. This is accompanied by mechanisms that promote inflammation, such as an increase in NF-κB and hypoxia-inducible factor-1α. Consequently, anti-inflammatory M2 macrophages convert to pro-inflammatory M1 macrophages, triggering a cytokine storm known to cause damage to endothelial tissue and organs in severe COVID-19 patients. The anti-inflammatory effects of melatonin in preventing pro-inflammatory profiles or macrophages and suppressing NF-κB activation may help reverse the Warburg effect in chronic COVID patients. Melatonin also regulates the metabolism of amyloid β (Aβ) associated with Alzheimer’s disease. Studies with transgenic Alzheimer’s disease models have shown that melatonin can control neuroinflammation by interacting with Aβ40 and Aβ42 and increasing protein degradation. In addition, melatonin’s ability to regulate circadian rhythms and sleep patterns has been shown to improve cognitive function and sleep in patients in the early stages of cognitive decline. Melatonin is also known to be therapeutic against the various symptoms of ME/CFS, such as oxidative stress, pro-inflammatory state, mitochondrial and bioenergetic dysregulation, and disruption of the gut/mucosa barrier.
conclusions
Overall, the review reported the important potential of using melatonin in long-term treatment of COVID-19 and COVID-19. Studies have shown that melatonin is more effective in reducing inflammatory markers of COVID-19 than antivirals commonly used for SARS-CoV-2. The authors believe that although melatonin exhibits anti-inflammatory and immunostimulatory properties that many studies have reported to be effective against COVID-19, it has not been promoted as a treatment option, possibly due to its easy availability and non-patent, which makes it unproven. attractive target for pharmaceutical industries. They recommend clinical trials to investigate the use of melatonin as a treatment for long-term COVID symptoms.
