What if melatonin could help COVID-19 severe patients?

Sánchez-González, Jul 2021
Mortality 54% improvement lower risk ← → higher risk Melatonin  Sánchez-González et al.  LATE TREATMENT Is late treatment with melatonin beneficial for COVID-19? Retrospective 448 patients in Spain Lower mortality with melatonin (p=0.0009) c19early.org Sánchez-González, July 2021 0 0.5 1 1.5 2+ RR
Melatonin for COVID-19
11th treatment shown to reduce risk in December 2020, now with p = 0.000000011 from 20 studies.
Lower risk for mortality, ventilation, and recovery.
No treatment is 100% effective. Protocols combine treatments.
6,200+ studies for 200+ treatments. c19early.org
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Retrospective 2,463 hospitalized patients in Spain, 265 treated with melatonin, showing lower mortality with treatment in PSM analysis, however these results are subject to immortal time bias. Authors excluded from the sample patients that died during the first 72 hours of admission without taking melatonin, and patients that started on melatonin in the last 7 days of their admittance, having completed 75% of their stay.
This study is excluded in the after exclusion results of meta analysis: immortal time bias may significantly affect results.
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risk of death, 54.4% lower, RR 0.46, p < 0.001, treatment 24 of 224 (10.7%), control 53 of 224 (23.7%), NNT 7.7, odds ratio converted to relative risk, PSM.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Sánchez-González et al., 20 Jul 2021, retrospective, Spain, peer-reviewed, 4 authors.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 Spain United Kingdom Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Georgia Switzerland Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR Spain favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 Spain United Kingdom Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Georgia Switzerland Bosnia-Herzegovina Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria Spain favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Abstract: https://doi.org/10.5664/jcsm.9554 LETTERS TO THE EDITOR What if melatonin could help patients with severe COVID-19?   Miguel Angel Sanchez-Gonzalez, MD, PhD1,2; Ignacio Mahıllo-Fernandez, PhD3; Felipe Villar-Alvarez, MD, PhD4; Lucıa Llanos, MD, PhD5 Psychiatry Department, Fundacion Jimenez Dıaz University Hospital, Health Research Institute (IIS-FJD, UAM), Madrid, Spain; 2Department of Anatomy, Histology, and Neuroscience, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain; 3Biostatistics Unit, Fundacion Jimenez Dıaz University Hospital, Health Research Institute (IIS-FJD, UAM), Madrid, Spain; 4Pulmonology Department, Fundacion Jimenez Dıaz University Hospital, Health Research Institute (IIS-FJD, UAM), CIBERES, Universidad Autonoma de Madrid, Madrid, Spain; 5Clinical Research Unit, Fundacion Jimenez Dıaz University Hospital, Health Research Institute (IIS-FJD, UAM), Madrid, Spain 1 Copyright 2022 American Academy of Sleep Medicine. All rights reserved. In March 2020, a protocol recommending the prescription of melatonin, among other sleep- and biorhythms-promoting measures, to hospitalized patients with coronavirus disease 2019 (COVID-19) with sleep problems or delirium was sent from the consultationliaison psychiatrist to the medical staff of the Fundaci on Jimenez Dıaz University Hospital (FJDUH) in Madrid, Spain. Several authors have suggested a potential benefit of melatonin use in COVID-19.1–4 In addition to its circadian function, melatonin is thought to have several health-promoting properties, including immune response modulation and anti-inflammatory and antioxidant properties.5 We here report a retrospective analysis showing an association of melatonin with survival in a sample of 2,463 Table 1—Unmatched and matched groups of melatonin and non-melatonin patient characteristics, and comparison of mortality and hospital stay between matched groups. Variable Demographics and clinical history Agea Female CVD DM Hypertension Lung disease Dyslipidemia Smoking habit Treatment-related ICU/IRCU stay Dexamethasone Tocilizumab Cyclosporine Methylprednisolone Anakinra Nasal cannula oxygen High-flow oxygen Clinical evolution Hospital stay, d Mortality Melatonin (n = 224) Unmatched Comparisons Matched Comparisons Non-Melatonin (n = 1,952) P Value Non-Melatonin (n = 224) P Value Effectb (95% CI) 69.0 (22.5) 96 (42.9%) 61 (27.2%) 53 (23.7%) 113 (50.4%) 54 (24.1%) 95 (42.4%) 14 (6.2%) 74.0 (28.0) 917 (47.0%) 594 (30.4%) 378 (19.4%) 1,052 (53.9%) 443 (22.7%) 738 (37.8%) 152 (7.8%) .054 .271 .362 .150 .363 .694 .204 .492 70.0 (25.0) 97 (43.3%) 62 (27.7%) 39 (17.4%) 112 (50.0%) 58 (25.9%) 80 (35.7%) 20 (8.9%) .982 > .99 > .99 .128 > .99 .743 .175 .372 — — — — — — — — 53 (23.7%) 42 (18.8%) 67 (29.9%) 138 (61.6%) 183 (81.7%) 11 (4.9%) 184 (82.1%) 34 (15.2%) 112 (5.7%) 109 (5.6%) 177 (9.1%) 677 (34.7%) 1,167 (59.8%) 13 (0.7%) 1,272 (65.2%) 82 (4.2%) <.001 <.001 <.001 <.001 <.001 <.001 <.001 <.001 43 (19.2%) 32 (14.3%) 71 (31.7%) 145 (64.7%) 192 (85.7%) 7 (3.1%) 171 (76.3%) 26 (11.6%) .300 .252 .759 .557 .306 .470 .162 .332 — — — — — — — — 13.7 (23.1) 24 (10.7%) 5.9 (6.7) 340 (17.4%) <.001 .014 8.9 (10.9) 53 (23.7%) <.001 <.001 4.8 (2.3–6.2) 0.39 (0.23–0.65) a Expressed as median (interquartile range). bMedian differences for hospital stay and odds ratio..
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
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