High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial

Alizadeh, Nafiseh; Dianatkhah, Mehrnoush; Alimohamadi, Yousef; Moradi, Hazhir; Akbarpour, Samaneh; Akrami, Majid; Mansouri, Fatemeh; Faraji, Neda; Rezaie, Zahra; Alizadeh, Mahboubeh; Hosamirudsari, Hadiseh

doi:10.1016/j.jtumed.2022.04.012

Cited by 14 publications

(29 citation statements)

References 38 publications

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“…7 ). In the 3 studies, [ 20 , 23 , 24 ] there was no significant difference in WBC count between the melatonin treated group and the control group (WMD = –1.07, 95% CI = –2.44, 0.30, P = .13) (Fig. 8 ).…”

Section: Resultsmentioning

confidence: 93%

“…One study did not mention the occurrence of adverse reactions. [ 20 , 24 ] Three studies [ 19 , 21 , 22 ] reported no adverse reactions during melatonin use. One study [ 23 ] indicated that 1 patient died in the intervention group.…”

Section: Resultsmentioning

confidence: 99%

“…In this meta-analysis, it selected only a few indicators for comparison without significant difference between the intervention group and the control group, which was related to the small number of studies, but the results were all of low heterogeneity. Three studies [ 19 , 20 , 24 ] mentioned that improvement was based on the alleviation of symptoms and indicators. In 2 studies, [ 21 , 23 ] the patients discharged from hospital and survival were used as improvement criteria.…”

Section: Discussionmentioning

confidence: 99%

“…Four studies [19,20,[22][23][24] mentioned changes in CRP after melatonin administration, and there was no significant difference in CRP between the melatonin group and the control group (weighted mean difference [WMD] = -0.36, 95%CI = -3.65, 2.92, P = .83) (Fig. 6).…”

Section: Secondary Outcomesmentioning

confidence: 99%

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The safety and efficacy of melatonin in the treatment of COVID-19: A systematic review and meta-analysis

Wang

Cai

et al. 2022

Medicine

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Background: As an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the common signs of coronavirus disease 2019 (COVID-19) are respiratory symptoms, fever, cough, shortness of breath, and dyspnea, with multiple organ injuries in severe cases. Therefore, finding drugs to prevent and treat COVID-19 is urgently needed and expected by the public. Several studies suggested beneficial effects of melatonin for the relevant prevention and treatment. To explore the effect and safety of melatonin in the treatment and provide theoretical support and reference for seeking the most suitable drug for COVID-19, the meta-analysis was carried out accordingly. Methods: It included randomized clinical trials of patients with COVID-19 treated with melatonin. Total effective rate was the primary outcome, while C-reactive protein (CRP), arterial oxygen saturation (SaO 2 ), white blood cell count (WBC) were the secondary measures. Random-effect and fixed-effect models were used to evaluate the effect size of some indicators in this meta-analysis. Results: Six eligible studies with 338 participants were included. One hundred seventy subjects were treated with melatonin adjuvant therapy and 168 subjects were assigned to the control group, with total excellent effective rate in subjects treated with melatonin [odds ratio = 3.05, 95 % confidence interval (CI) = 1.47, 6.31, P = .003]. Homogeneity was analyzed by fixed effect model ( I 2 = 0%). There was no significant difference in CRP between the melatonin group and the control group (weighted mean difference [WMD] = –0.36, 95% CI = –3.65, 2.92, P = .83). Significant difference was not existed in SaO 2 between the melatonin treatment group and the control group (WMD = 1, 95% CI = –1.21, 3.22, P = .37). In terms of WBC, there was no significant difference between the 2 groups (WMD = –1.07, 95% CI = –2.44, 0.30, P = .13). Conclusions: The meta-analysis showed that melatonin had the beneficial effects for COVID-19 prevention and treatment as an adjunctive agent in combination with basic treatment for the treatment.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Secondary Outcomesmentioning

confidence: 99%

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The safety and efficacy of melatonin in the treatment of COVID-19: A systematic review and meta-analysis

Wang

Cai

et al. 2022

Medicine

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“…Under severe inflammatory circumstances, melatonin is typically effective in protecting cells from oxidative damage. One study discovered that melatonin adjuvant therapy helped patients with COVID-19 disease by reducing inflammatory cytokines and improving disease control [ 77 ]. Additionally, the researchers stated that melatonin therapy at a dose of 9 mg per day for 14 days affected the expression of genes linked to the humoral and cellular immune systems Th1 and Th2 receptors [ 78 ].…”

Section: Melatonin’s Anti-inflammatory Effectsmentioning

confidence: 99%

Potential Therapeutic Approach of Melatonin against Omicron and Some Other Variants of SARS-CoV-2

et al. 2022

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The Omicron variant (B.529) of COVID-19 caused disease outbreaks worldwide because of its contagious and diverse mutations. To reduce these outbreaks, therapeutic drugs and adjuvant vaccines have been applied for the treatment of the disease. However, these drugs have not shown high efficacy in reducing COVID-19 severity, and even antiviral drugs have not shown to be effective. Researchers thus continue to search for an effective adjuvant therapy with a combination of drugs or vaccines to treat COVID-19 disease. We were motivated to consider melatonin as a defensive agent against SARS-CoV-2 because of its various unique properties. Over 200 scientific publications have shown the significant effects of melatonin in treating diseases, with strong antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has a high safety profile, but it needs further clinical trials and experiments for use as a therapeutic agent against the Omicron variant of COVID-19. It might immediately be able to prevent the development of severe symptoms caused by the coronavirus and can reduce the severity of the infection by improving immunity.

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Melatonin’s Benefits as a Treatment for COVID-19 Pandemic and Long COVID

Cardinali

Brown

Pandi‐Perumal

2023

Progress in Sleep Research

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High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial

Cited by 14 publications

References 38 publications

The safety and efficacy of melatonin in the treatment of COVID-19: A systematic review and meta-analysis

The safety and efficacy of melatonin in the treatment of COVID-19: A systematic review and meta-analysis

Potential Therapeutic Approach of Melatonin against Omicron and Some Other Variants of SARS-CoV-2

Melatonin’s Benefits as a Treatment for COVID-19 Pandemic and Long COVID

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