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

Abstract

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.

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

“…The aim was to determine if any single study was responsible for the significant results observed. After excluding either the study by Ameri et al (32) or Alizadeh et al (13), the pooled relative risk decreased significantly from 0.72 to 0.31. However, we did not observe any noticeable decrease in heterogeneity during the one-by-one exclusion process.…”

“…The average age of the patients was above 55 in two studies (13,15), and below 55 in the other three studies (29, 31, 32). The severity of COVID-19 in the enrolled patients was severe in three studies (13,15,32).…”

“…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).…”

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

“…In a prospective randomized clinical trial of severe COVID-19 in Iraq, 82 patients were administered melatonin (standard therapy plus 10 mg melatonin daily for two weeks), while 76 patients were provided standard therapy only; the melatonin-treated group presented less thrombosis and sepsis events after adjusting for other confounding factors and lower mortality (melatonin group vs. control group: 1.2% vs. 17.1%) [ 168 ]. In another randomized controlled trial of melatonin treatment for hospitalized Iranian patients with severe COVID-19, a total of 109 patients in the melatonin group (adjuvant 5 mg melatonin twice daily for 7 days) and 117 patients in the control group (standard therapy only) were enrolled in the study [ 169 ]. The mortality rate was 67% in the melatonin group compared with 94% in the control group.…”

Development of indolealkylamine derivatives as potential multi-target agents for COVID-19 treatment

“…Further favorable effects of melatonin receptors in the COVID-19 context are their synchronizing effect on biological rhythms and their sleep-initiating properties that might be beneficial for intensive care patients suffering from disrupted sleep patterns or sleep deprivation, which favors the production of inflammatory cytokines and predisposition to lung inflammation [ 30 ]. First results from clinical trials on the effect of melatonin in critically ill patients with SARS-CoV-2 infection report a significantly improved clinical status when given as an adjunctive agent in combination with basic treatments in some studies but not in others without any apparent adverse events (Ref) [ [31] , [32] , [33] , [34] ].…”