COVID-19

Medical Studies on Melatonin

A Review of the Potential Effects of Melatonin in Compromised Mitochondrial Redox Activities in Elderly Patients With COVID-19

2022-06 Su WL, Wu CC, Wu SV, Lee MC, Liao MT, Lu KC, Lu CL

Melatonin, an endogenous indoleamine, is an antioxidant and anti-inflammatory molecule widely distributed in the body. It efficiently regulates pro-inflammatory and anti-inflammatory cytokines under various pathophysiological conditions. The melatonin rhythm, which is strongly associated with oxidative lesions and mitochondrial dysfunction, is also observed during the biological process of aging. Melatonin levels decline considerably with age and are related to numerous age-related illnesses.

Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels

2022-06 Cecon E, Fernandois D, Renault N, Coelho CFF, Wenzel J, Bedart C, Izabelle C, Gallet S, Le Poder S, Klonjkowski B, Schwaninger M, Prevot V, Dam J, Jockers R

COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post-COVID state. Brain infection is particularly pronounced in the K18-hACE2 mouse model of COVID-19. Prevention of brain infection in the acute phase of the disease might thus be of therapeutic relevance to prevent long-lasting symptoms of COVID-19.

Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia

2022-06 Chilosi M, Doglioni C, Ravaglia C, Martignoni G, Salvagno GL, Pizzolo G, Bronte V, Poletti V

Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review.

Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

2022-02 Reiter RJ, Sharma R, Simko F, Dominguez-Rodriguez A, Tesarik J, Neel RL, Slominski AT, Kleszczynski K, Martin-Gimenez VM, Manucha W, Cardinali DP

Numerous pharmaceutical drugs have been repurposed for use as treatments for COVID-19 disease. These drugs have not consistently demonstrated high efficacy in preventing or treating this serious condition and all have side effects to differing degrees. We encourage the continued consideration of the use of the antioxidant and anti-inflammatory agent, melatonin, as a countermeasure to a SARS-CoV-2 infection.

Melatonin reduces the mortality of severely-infected COVID-19 patients

2021-12 Tan DX, Reiter RJ

SARS-CoV-2 has ravaged the population of the world for two years. Scientists have not yet identified an effective therapy to reduce the mortality of severe COVID-19 patients. In a single-center, open-label, randomized clinical trial, it was observed that melatonin treatment lowered the mortality rate by 93% in severely-infected COVID-19 patients compared with the control group (see below). This is seemingly the first report to show such a huge mortality reduction in severe COVID-19 infected individuals with a simple treatment. If this observation is confirmed by more rigorous clinical trials, melatonin could become an important weapon to combat this pandemic.

A preliminar study of a neuroimmune regimen with low-dose angiotensin 1-7 plus melatonin to improve the safety of covid 19 vaccine

2021-06 Lissoni P, Rovelli F, Messina G, Monzon A, Colciago M, Valentini A, Di Fede G, Cardinali DP

In experimental conditions, it has been demonstrated that vaccine efficacy and the toxicity is depending on cytokine-induced immunoinflammatory response, and that they may be modulate through a neuroimmune approach, which neuroendocrine agents, such as the pineal hormone melatonin (MLT) and the enzymatic product of ACE2, the angiotensin 1-7 (Ang 1-7). On these bases, a preliminary study was planned to evaluate the influence of an oral peri-vaccination regimen with MLT plus Ang 1-7 on the subjective safety of Covid19 Pfizer-BioNTech (PF) and AstraZeneca (AZ) vaccines.

Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial

2021-06 Farnoosh G, Akbariqomi M, Badri T, Bagheri M, Izadi M, Saeedi-Boroujeni A, Rezaie E, Ghaleh HEG, Aghamollaei H, Fasihi-ramandi M, Hassanpour K, Alishiri GH

Melatonin has been known as an anti-inflammatory agent and immune modulator that may address progressive pathophysiology of coronavirus disease 2019 (COVID-19). Aim of the study. To evaluate the clinical efficacy of adjuvant, use of melatonin in patients with COVID-19.

Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment

2021-05 Hosseini A, Esmaeili Gouvarchin Ghaleh H, Aghamollaei H, Fasihi Ramandi M, Alishiri G, Shahriary A, Hassanpour K, Tat M, Farnoosh G 

Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease.

Inflammation, immunity and potential target therapy of SARS-COV-2: A total scale analysis review

2021-04 Smail SW, Saeed M, Alkasalias T, Khudhur ZO, Younus DA, Rajab MF, Abdulahad WH, Hussain HI, Niaz K, Safdar M

Coronavirus disease-19 (COVID-19) is a complex disease that causes illness ranging from mild to severe respiratory problems. It is caused by a novel coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) that is an enveloped positive-sense single-stranded RNA (+ssRNA) virus belongs to coronavirus CoV family.

SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin

2021-03 Mehrzadi S, Karimi MY, Fatemi A, Reiter RJ, Hosseinzadeh A

Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities.

Role of Melatonin on Virus-Induced Neuropathogenesis-A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection.

2021-01 Wongchitrat P, Shukla M, Sharma R, Govitrapong P, Reiter RJ

Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common.

A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19

2020-10 Zhou Y, Hou Y, Shen J, Kallianpur A, Zein J, Culver DA, Farha S, Comhair S, Fiocchi C, Gack MU, Mehra R, Stappenbeck T, Chan T, Eng C, Jung JU, Jehi L, Erzurum S, Cheng F

The global Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations.

Melatonin is significantly associated with survival of intubated COVID-19 patients

2020-10 Ramlall V, Zucker J, Tatonetti N

Respiratory distress requiring intubation is the most serious complication associated with coronavirus disease 2019 (COVID-19). In this retrospective study, we used survival analysis to determine whether or not mortality following intubation was associated with hormone exposure in patients treated at New York Presbyterian/ Columbia University Irving Medical Center. Here, we report the overall hazards ratio for each hormone for exposure before and after intubation for intubated and mechanically ventilated patients.

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

2020-09 Tan DX, Hardeland R

Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen's spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution.

Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19

2020-09 El-Missiry MA, El-Missiry ZMA, Othman AI

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages.

Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment

2020-08 Martín Giménez VM, Inserra F, Tajer CD, Mariani J, Ferder L, Reiter RJ, Manucha W

COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level.

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

2020-07 Hazra S, Chaudhuri AG, Tiwary BK, Chakrabartia N

The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19.

Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series

2020-06 Castillo RR, Quizon GRA, Juco MJM, Roman ADE, de Leon DG, Punzalan FER, Guingon RBL, Morales DD, Tan DX, Reiter RJ

Treatment for coronavirus disease 2019 (COVID19) pneumonia remains empirical and the search for therapies that can improve outcomes continues. Melatonin has been shown to have anti-inflammatory, antioxidant, and immune-modulating effects that may address key pathophysiologic mechanisms in the development and progression of acute respiratory distress syndrome (ARDS), which has been implicated as the likely cause of death in COVID19.

Can melatonin reduce the severity of COVID-19 pandemic?

2020-04 Shneider A, Kudriavtsev A, Vakhrusheva A

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 life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks.

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