Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed

Kleszczyński, Konrad; Slominski, Andrzej; Steinbrink, Kerstin; Reíter, Russel J.

doi:10.3390/nu12092561

Cited by 50 publications

(61 citation statements)

References 84 publications

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“…Melatonin is an endogenously produced molecule in small amounts with presumed anti-inflammatory, antioxidant, and antiviral effects [ 49 ]. Melatonin was considered as treatment in sepsis due to its anti-inflammatory, antiapoptotic, and powerful antioxidant properties [ 50 ] and further proposed for SARS-CoV-2 treatment [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Perceptions of Romanian Physicians on Lockdowns for COVID-19 Prevention

Dima

Balaban

Jurcuţ³

et al. 2021

Healthcare

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) was declared a pandemic in March 2020, triggering important changes for the entire society and healthcare systems, as well as significant lockdown measures aimed to limit the disease spread. We herein intended to catch the dynamic of Romanian physicians’ perceptions of COVID-19 impact. For this purpose, after a literature review, a 30-item questionnaire was designed. The questionnaire was twice distributed online, about 1 month apart, during which partial relaxation measures were decreed in Romania. The questionnaire was voluntarily filled in by Romanian physicians who were willing to participate in the study. A total of 214 physicians answered the questionnaire upon its first release, and 199 respondents were registered upon its second release, most of whom (94.9%) were involved in clinical work, with one-third working in units dedicated to COVID-19 patients. In parallel with the relaxation of lockdown measures, along with increased confidence in the efficiency of protective measures (46.7% vs. 31.3%), separation from household members decreased from 36.9% to 22.1%. Nevertheless, the feeling of rejection felt by doctors remained similar (22.4% vs. 24.6%). Furthermore, answers regarding the clinical picture, diagnostic approach, and treatment options are discussed. Most of therapeutic options considered for SARS-CoV-2 treatment (e.g., lopinavir/ritonavir, oseltamivir, hydroxychloroquine, azithromycin, tocilizumab, and convalescent plasma) failed to confirm significant efficiency. On the contrary, vaccines for widescale use are already available despite the initial skepticism. In the beginning of the pandemic, 25.2% (18.2% vs. 32.2%) considered that there will not be an effective COVID-19 vaccine, while 41.6% (43.0% vs. 40.2%) thought that a vaccine would be available after at least 12 months. In conclusion, initially, following only a 1 month period, Romanian physicians’ intention to consider treatments such as hydroxychloroquine or lopinavir/ritonavir for COVID-19 decreased significantly. Moreover, confidence in the efficiency of available protective measures increased, and the rates of separation from household members decreased.

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Section: Discussionmentioning

confidence: 99%

Perceptions of Romanian Physicians on Lockdowns for COVID-19 Prevention

Dima

Balaban

Jurcuţ³

et al. 2021

Healthcare

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“…Similar dose of melatonin (8.1 mg/kg/day and 8.2 mg/kg/day) has been used in a prospective nonrandomized nonblind case–control study on neonates with neonatal sepsis ( El-Gendy, El-Hawy, & Hassan, 2018 ). Since no adverse effects have been reported by this clinical study, it is estimated that a daily dose of 600 mg of melatonin may be useful for treatment of deadly viral infectious diseases, including COVID-19 ( Kleszczyński et al, 2020 ). A case series study performed by Castillo et al evaluated the effect of melatonin (36–72 mg/day) as an adjuvant therapy in 10 patients admitted with COVID19 pneumonia.…”

Section: Melatoninmentioning

confidence: 90%

“…Furthermore, severely affected ALS patients treated with 300 mg/day melatonin for 2 years did not show any adverse effects ( Weishaupt et al, 2006 ). Due to the destructive inflammation in severe COVID-19 patients, the sufficient amounts of melatonin are required to overcome SARS-CoV-2-induced pathological alterations; this goal is not achieved with physiological levels of melatonin ( Kleszczyński, Slominski, Steinbrink, & Reiter, 2020 ). Administration of melatonin in mice infected with H1N1 virus could reduce the mortality in a dose of 100 mg/kg/day (200 mg/kg/48 h) ( Huang et al, 2019 ).…”

Section: Melatoninmentioning

confidence: 99%

“…Administration of melatonin in mice infected with H1N1 virus could reduce the mortality in a dose of 100 mg/kg/day (200 mg/kg/48 h) ( Huang et al, 2019 ). Conversion of murine dose to the human dose results in a human equivalent dose for melatonin of 8.1 mg/kg/day, a daily dose of 600 mg for a 75-kg human ( Kleszczyński et al, 2020 ). Similar dose of melatonin (8.1 mg/kg/day and 8.2 mg/kg/day) has been used in a prospective nonrandomized nonblind case–control study on neonates with neonatal sepsis ( El-Gendy, El-Hawy, & Hassan, 2018 ).…”

Section: Melatoninmentioning

confidence: 99%

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

Mehrzadi

Karimi

Fatemi

et al. 2021

Pharmacology & Therapeutics

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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. Results from several studies suggest that CoVs localize in mitochondria and interact with mitochondrial protein translocation machinery to target their encoded products to mitochondria. Coronaviruses encode a number of proteins; this process is essential for viral replication through inhibiting degradation of viral proteins and host misfolded proteins including those in mitochondria. These viruses seem to maintain their replication by altering mitochondrial dynamics and targeting mitochondrial-associated antiviral signaling (MAVS), allowing them to evade host innate immunity. Coronaviruses infections such as COVID-19 are more severe in aging patients. Since endogenous melatonin levels are often dramatically reduced in the aged and because it is a potent anti-inflammatory agent, melatonin has been proposed to be useful in CoVs infections by altering proteasomal and mitochondrial activities. Melatonin inhibits mitochondrial fission due to its antioxidant and inhibitory effects on cytosolic calcium overload. The collective data suggests that melatonin may mediate mitochondrial adaptations through regulating both mitochondrial dynamics and biogenesis. We propose that melatonin may inhibit SARS-CoV-2-induced cell damage by regulating mitochondrial physiology.

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“…Delirium is a consciousness disorder with cognitive change (hyperactive, hypoactive, or mixed form) and is a well-known risk factor for prolonged duration of intensive care unit (ICU) stay, higher mortality, greater risk of cognitive sequelae, and more hospital costs (1). The potentiality of melatonin, a molecule of unusual phylogenetic conservation present in all known aerobic organisms, to serve as a preventive and therapeutic agent in COVID-19 pandemic has been advocated (2,3). Melatonin (a) may prevent SARS-CoV-2 infection; (b) is suitable as an effective anti-inflammatory/immunoregulatory/antioxidant agent; (c) counteracts chronodisruption; (d) combats several comorbidities such as diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases, which aggravate COVID-19 disease; (e) exerts a neuroprotective effect in acutely and chronically affected SARS-CoV-2 patients; and (f) can be an adjuvant to potentiate anti-SARS-CoV-2 vaccines (see for ref.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of melatonin in non-intensive care unit patients with COVID-19 pneumonia and sleep dysregulation

et al. 2021

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The association of sleep disruption with a higher vulnerability to COVID-19 infection is a subject of major clinical importance. In patients with pneumonia associated with COVID-19 admitted to non-intensive care unit (NICU) several factors, like the disrupting influence of respiratory distress, medication, greater stress due to social isolation, and lack of appropriate exposure to environmental light can be instrumental to disrupt sleep/wake cycle. The therapeutic potential of melatonin to counteract the consequences of COVID-19 infection has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. Melatonin is also an effective chronobiotic agent to reverse the circadian disruption of social isolation and to control delirium in severely affected patients. Properly administered, melatonin may restore the optimal circadian pattern of the sleep-wake cycle and improve clinical condition in pneumonia associated with COVID-19 patients. The present review article discusses the importance of maintaining normal sleep and circadian rhythmicity in NICU patients and provides preliminary data suggesting the efficacy of melatonin (9 mg/day) to reduce length of stay of pneumonia patients associated with COVID-19 in NICU.

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Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed

Cited by 50 publications

References 84 publications

Perceptions of Romanian Physicians on Lockdowns for COVID-19 Prevention

Perceptions of Romanian Physicians on Lockdowns for COVID-19 Prevention

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

Efficacy of melatonin in non-intensive care unit patients with COVID-19 pneumonia and sleep dysregulation

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