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Melatonin as adjuvant treatment in COVID-19 patients. A meta-analysis of randomized and propensity matched studies

  • Krisztina Tóth1
  • Eros Pilia2
  • Giovanni Landoni3,4,*,
  • Davide Oreggia3
  • Salvatore Giacomarra3
  • Rosario Losiggio3
  • Giacomo Maiucci3
  • Iliyan Vlasakov3
  • Andrey Yavorovskiy5
  • Valery Likhvantsev5,6
  • Andrea Székely7
  • Remo Daniel Covello8

1Doctoral School of Theoretical and Translational Medicine, Semmelweis University, 1089 Budapest, Pest, Hungary

2Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy

3Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy

4Faculty of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy

5I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia

6Federal Research and Clinical Center of Resuscitation and Rehabilitation, 107031 Moscow, Russia

7Department of Anesthesia, Semmelweis University, 1082 Budapest, Pest, Hungary

8Anesthesia and Intensive Care Unit, Emergency Department, Busto Arsizio Hospital, ASST Valle Olona, 21052 Busto Arsizio, Varese, Italy

DOI: 10.22514/sv.2023.076 Vol.20,Issue 1,January 2024 pp.8-16

Submitted: 05 March 2023 Accepted: 07 April 2023

Published: 08 January 2024

*Corresponding Author(s): Giovanni Landoni E-mail:


Melatonin is a neurohormone well-known as sleep disorder treatment. A few clinical trials have recently pointed out the biological plausibility of utilising melatonin in the treatment of coronavirus disease 2019 (COVID-19, SARS-CoV-2) patients. Melatonin wide range of activities include anti-inflammatory, antiviral and antioxidant effects. Our meta-analysis aimed to investigate the effect of melatonin on mortality in COVID-19 patients with different disease severity. We searched PubMed, EMBASE, Web of Science with no language restrictions updated on February 2023 for randomized and propensity matched studies, comparing melatonin plus standard COVID-19 therapy vs. standard COVID-19 therapy alone. Patients had to be hospitalised with a confirmed diagnosis of SARS-CoV-2 infection. Primary outcome was mortality at the longest follow-up available. We included 7 randomized and 1 propensity matched studies enrolling 1155 overall patients with a mean age of 61 ± 19.5 years. We found a reduced mortality rate in the overall population (127/575 (22%) vs. 209/580 (36%) Relative Risk: 0.62 (confidence interval (CI): 0.40, 0.96), I2 = 86% p = 0.03, with the results confirmed when pooling the 5 studies which administered melatonin in non-intensive-care-unit patients (26/423 (6.1%) vs. 69/419 (16%) Relative Risk 0.30 (CI: 0.10, 0.86), I2 = 40% p = 0.02). According to recent randomized and propensity matched evidence, melatonin might be a life-saving adjuvant therapy in COVID-19 patients. This effect was mainly driven by non-intensive care unit patients.


Melatonin; COVID-19; SARS-CoV-2; Mortality; Critical care; Intensive care unit

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Krisztina Tóth,Eros Pilia,Giovanni Landoni,Davide Oreggia,Salvatore Giacomarra,Rosario Losiggio,Giacomo Maiucci,Iliyan Vlasakov,Andrey Yavorovskiy,Valery Likhvantsev,Andrea Székely,Remo Daniel Covello. Melatonin as adjuvant treatment in COVID-19 patients. A meta-analysis of randomized and propensity matched studies. Signa Vitae. 2024. 20(1);8-16.


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