A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19

Fogleman, Corey D.; Cohén, Donna; Mercier, Alison; Farrell, Daniel; Rutz, Jennifer; Bresz, Kellie; Vernon, Tawnya M.

doi:10.3122/jabfm.2022.04.210529

Cited by 17 publications

(33 citation statements)

References 22 publications

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“…Anderson et al demonstrated melatonin could improve some COVID-19 symptoms consistent with our obtained results (Anderson and Reiter 2020 ). Randomized controlled trial conducted in Lancaster County, Pennsylvania, United states had shown oral melatonin could improve clinical symptoms in mild–moderate COVID-19 patient during 14 days of intervention and improve life quality (Fogleman et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial

et al. 2022

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Patients with COVID-19 have shown melatonin deficiency. We evaluated the efficacy and safety of administration oral melatonin in patients with COVID-19-induced pneumonia. Patients were randomly assigned in a 1:1 ratio to receive melatonin plus standard treatment or standard treatment alone. The primary outcomes were mortality rate and requirement of IMV. The clinical status of patients was recorded at baseline and every day over hospitalization based on seven-category ordinal scale from 1 (discharged) to 7 (death). A total of 226 patients (109 in the melatonin group and 117 in the control group) were enrolled (median age; in melatonin group: 54.60 ± 11.51, in control group: 54.69 ± 13.40). The mortality rate was 67% in the melatonin group and 94% in the control group (OR; 7.75, 95% CI, 3.27–18.35, P < 0.001). The rate of IMV requirement was 51.4% in the melatonin group and 70.9% in the control group, for an OR of 2.31 (95% CI, 1.34–4.00, P < 0.001). The median number of days to hospital discharge was 15 days (13–17) in the melatonin group and 21 days (14–24) in the control group (OR; 5.00, 95% CI, 0.15–9.84, P = 0.026). Time to clinical status improvement by ≥ 2 on the ordinal scale in was 12 days (9–13) in the melatonin group and 16 days (10–19) in the control group (OR; 3.92, 95% CI, 1.69–6.14, P = 0.038). Melatonin significantly improved clinical status with a safe profile in patients with severe COVID-19 pneumonia. Supplementary Information The online version contains supplementary material available at 10.1007/s10787-022-01096-7.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial

et al. 2022

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“…A total of 140 records were screened during the electronic database searching process, and two additional studies were retrieved by screening reference lists of related articles. Eventually, nine RCTs involving 718 subjects were identified and included in the final meta-analyses (13)(14)(15)(27)(28)(29)(30)(31)(32). In the experimental group, the intervention consisted of melatonin plus standard care, while in the control group, nearly all comparators were standard care alone (15,(27)(28)(29)(30)(31)(32), except for two studies that included a matched placebo (13,14) (Supplementary Table 2).…”

Section: Description Of Included Studiesmentioning

confidence: 99%

“…However, these findings were based on small numbers of randomized controlled trials (RCTs). Recently, more RCTs with larger sample sizes have been published, but with opposing results and findings (13)(14)(15). To resolve this conflicting issue, we conducted this Abbreviations: CIs, confidence intervals; COVID-19, coronavirus pandemic disease 2019; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ICU, intensive care units; ITT, intention-to-treat; MDs, mean differences; NLR, neutrophil to lymphocyte ratio; PP, per-protocol; PRISMA, preferred reporting items for systematic review and meta-analysis; RCTs, randomized controlled trials; RoB, risk-of-bias; RR, relative risk; TSA, trial sequential analysis; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.…”

Section: Introductionmentioning

confidence: 99%

The clinical efficacy of melatonin in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

Huang

Liu

et al. 2023

Front. Med.

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BackgroundThe COVID-19 pandemic has resulted in significant morbidity and mortality worldwide, with cytokine storm leading to exaggerating immune response, multi-organ dysfunction and death. Melatonin has been shown to have anti-inflammatory and immunomodulatory effects and its effect on COVID-19 clinical outcomes is controversial. This study aimed to conduct a meta-analysis to evaluate the impact of melatonin on COVID-19 patients.MethodsPubMed, Embase, and Cochrane Central Register of Controlled Trials were searched without any language or publication year limitations from inception to 15 Nov 2022. Randomized controlled trials (RCTs) using melatonin as therapy in COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included were the recovery rate of clinical symptoms, changes in the inflammatory markers like C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR). A random-effects model was applied for meta-analyses, and further subgroup and sensitivity analyses were also conducted.ResultsA total of nine RCTs with 718 subjects were included. Five studies using melatonin with the primary outcome were analyzed, and the pooled results showed no significant difference in mortality between melatonin and control groups with high heterogeneity across studies identified (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.47–1.11, p = 0.14, I2 = 82%). However, subgroup analyses revealed statistically significant effects in patients aged under 55 years (RR 0.71, 95% CI 0.62–0.82, p < 0.01) and in patients treated for more than 10 days (RR 0.07, 95% CI 0.01–0.53, p = 0.01). The recovery rate of clinical symptoms and changes in CRP, ESR, and NLR were not statistically significant. No serious adverse effects were reported from melatonin use.ConclusionIn conclusion, based on low certainty of evidence, the study concluded that melatonin therapy does not significantly reduce mortality in COVID-19 patients, but there are possible benefits in patients under 55 years or treated for more than 10 days. With a very low certainty of evidence, we found no significant difference in the recovery rate of COVID-19 related symptoms or inflammatory markers in current studies. Further studies with larger sample sizes are warranted to determine the possible efficacy of melatonin on COVID-19 patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022351424.

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“…In a pilot study conducted on the quality of life of patients in the US with mild to moderate COVID-19 severity, 32 patients who were supplemented with 10 mg of melatonin daily for 14 days had a more rapid improvement in their quality of life than the placebo group of 34 patients [ 166 ]. In a randomized single-blind pilot study of Iranian patients with mild to moderate COVID-19 severity, 14 patients received 6 mg of melatonin for 2 weeks.…”

Section: Melatonin and Covid-19mentioning

confidence: 99%

Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment

Yiang

et al. 2023

Viruses

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Aging processes, including immunosenescence, inflammation, inflammasome formation, genomic instability, telomeric attrition, and altered autophagy, are involved in viral infections and they may contribute to increased pathophysiological responses to the SARS-CoV-2 infection in the elderly; this poses additional risks of accelerated aging, which could be found even after recovery. Aging is associated with oxidative damage. Moreover, SARS-CoV-2 infections may increase the production of reactive oxygen species and such infections will disturb the Ca++ balance via an endoplasmic reticulum (ER) stress-mediated unfolded protein response. Although vaccine development and anti-inflammation therapy lower the severity of COVID-19, the prevalence and mortality rates are still alarming in some countries worldwide. In this review, we describe the involvement of viral proteins in activating ER stress transducers and their downstream signals and in inducing inflammation and inflammasome formation. Furthermore, we propose the potential of melatonin as an ER stress modulator, owing to its antioxidant, anti-inflammatory, and immunoregulatory effects in viral infections. Considering its strong safety profile, we suggest that additive melatonin supplementation in the elderly could be beneficial in treating COVID-19.

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A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19

Cited by 17 publications

References 22 publications

Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial

Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial

The clinical efficacy of melatonin in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment

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