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20 melatonin COVID-19 controlled studies, 9 RCTs
Supplementary Data — Melatonin reduces COVID-19 risk: real-time meta analysis of 20 studies
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0.75
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2+ Lissoni 91% 0.09 [0.01-1.57] 20mg hosp. 0/30 5/30 CT​1 ​ Improvement, RR [CI] Dose (1d) Treatment Control Alizadeh (SB RCT) 73% 0.27 [0.07-1.05] 6mg no recov. 2/14 9/17 Ramlall (ICU) 87% 0.13 [0.08-0.22] n/a death 196 (n) 752 (n) Intubated patients Darban (RCT) 33% 0.67 [0.14-3.17] 24mg progression 2/10 3/10 ICU patients CT​1 ​ Darban (RCT) 6% 0.94 [0.84-1.06] 24mg ICU 10 (n) 10 (n) ICU patients CT​1 ​ Hosseini 48% 0.52 [0.36-0.77] 9mg recov. time 20 (n) 20 (n) Farnoosh (DB RCT) 81% 0.19 [0.01-3.65] 9mg ICU 0/24 2/20 Farnoosh (DB RCT) 49% 0.51 [0.32-0.81] 9mg recov. time 24 (n) 20 (n) Farnoosh (DB RCT) 44% 0.56 [0.10-3.00] 9mg no disch. 2/24 3/20 Farnoosh (DB RCT) 43% 0.57 [0.35-0.92] 9mg no disch. 24 (n) 20 (n) Sánchez-González 54% 0.46 [0.28-0.71] varies death 24/224 53/224 Mousavi (RCT) 67% 0.33 [0.04-3.09] 3mg death 1/48 3/48 Mousavi (RCT) 40% 0.60 [0.24-1.52] 3mg ICU 6/48 10/48 Hasan (RCT) 93% 0.07 [0.01-0.53] 10mg death 1/82 13/76 Bologna 50% 0.50 [0.13-1.86] 2mg death 3/40 6/40 Bologna 50% 0.50 [0.13-1.86] 2mg ICU 3/40 6/40 Bologna 9% 0.91 [0.83-1.00] 2mg hosp. time 40 (n) 40 (n) Bologna 39% 0.61 [0.53-0.71] 2mg s-i time 40 (n) 40 (n) Bologna 58% 0.42 [0.33-0.52] 2mg NIV time 40 (n) 40 (n) Bologna 8% 0.92 [0.78-1.09] 2mg HFO time 40 (n) 40 (n) Bologna 18% 0.82 [0.74-0.90] 2mg sleep 40 (n) 40 (n) Bologna 33% 0.67 [0.54-0.82] 2mg delirium 40 (n) 40 (n) Sánchez-Rico 19% 0.81 [0.61-1.08] 2mg death Karimpour-.. (ICU) 39% 0.61 [0.21-1.76] 15mg death 5/12 13/19 ICU patients Karimpour-.. (ICU) 43% 0.57 [0.28-1.18] 15mg ventilation time 12 (n) 19 (n) ICU patients Karimpour-.. (ICU) 2% 0.98 [0.81-1.19] 15mg ICU 12 (n) 19 (n) ICU patients Alizadeh (DB RCT) 4% 0.96 [0.80-1.16] 21mg death 28/33 30/34 Intubated patients Alizadeh (DB RCT) 14% 0.86 [0.70-1.06] 21mg no recov. 26/33 31/34 Intubated patients Alizadeh (DB RCT) 27% 0.73 [0.51-1.05] 21mg ventilation time 33 (n) 34 (n) Intubated patients Fogleman (DB RCT) 17% 0.83 [0.55-1.25] recovery 32 (n) 34 (n) Ameri (RCT) 29% 0.71 [0.62-0.82] 10mg death 73/109 110/117 ICU patients Ameri (RCT) 28% 0.72 [0.58-0.90] 10mg ventilation 56/109 83/117 ICU patients Ameri (RCT) 25% 0.75 [0.63-0.89] 10mg no recov. 109 (n) 117 (n) ICU patients Ameri (RCT) 25% 0.75 [0.57-0.98] 10mg recov. time 109 (n) 117 (n) ICU patients Ameri (RCT) 29% 0.71 [0.53-0.96] 10mg hosp. time 109 (n) 117 (n) ICU patients Tian (ICU) 47% 0.53 [0.34-0.83] death 301 (n) 301 (n) ICU - ramelteon Sánchez-Gar.. (ICU) 42% 0.58 [0.41-0.83] varies death 42/202 48/133 ICU patients Jehi 58% 0.42 [0.26-0.68] n/a cases 16/529 802/11,143 Jehi 100% 0.00 [0.00-2.68] n/a cases 0/18 290/2,005 Zhou (PSM) 21% 0.79 [0.65-0.94] n/a cases MeCOVID GarcÃa-G.. (DB RCT) 7% 0.93 [0.06-14.7] 2mg symp. case 1/163 1/151 MeCOVID GarcÃa-G.. (DB RCT) -108% 2.08 [0.66-6.63] 2mg cases 9/163 4/151 Melatonin COVID-19 outcomes c19 early .org October 2025 ​1 ​ CT: study uses combined treatment Favors melatonin Favors control
Fig. S2. Comparison of results for RCTs versus observational studies.
For COVID-19 treatments, there is no significant difference between the results of RCTs and observational studies. Observational studies do not systematically over or underestimate efficacy. For high-cost treatments, there is a non-significant trend towards RCTs showing greater efficacy.
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