Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study
Sánchez-Rico et al.,
Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective..,
Journal of Travel Medicine, doi:10.1093/jtm/taab195
Retrospective database analysis in France with 272 patients treated with melatonin, showing 19% lower mortality after adjustments, without statistical significance. Risk was lower for higher dosage (not statistically significant). Age was only in three age ranges and severe COVID was binary, likely leading to substantial residual confounding. Unadjusted differences were extreme with 60% >80 years old for melatonin compared to 15% for control. Mean daily dose 2.61mg. The title of the paper is incorrect, the most adjusted results show melatonin did reduce mortality (without reaching statistical significance).
risk of death, 19.0% lower, RR 0.81, p = 0.15, treatment 82 of 272 (30.1%), control 6,487 of 58,290 (11.1%), adjusted per study, model b.
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Sánchez-Rico et al., 5 Feb 2022, retrospective, France, peer-reviewed, 6 authors, study period 24 January, 2020 - 31 October, 2021.
Abstract: Journal of Travel Medicine, 2022, 1–3
https://doi.org/10.1093/jtm/taab195
Research Letter
Research Letter
Marina Sánchez-Rico, MPH1,2,* , Pedro de la Muela, MPH1,2,
Juan J. Herrera-Morueco, MPH1,2, Pierre A. Geoffroy, MD3,4,5,
Frédéric Limosin, MD1,6,7 and Nicolas Hoertel, MD1,6,7 , On behalf of
AP-HP/Université de Paris/INSERM COVID-19 Research Collaboration/AP-HP COVID
CDR Initiative/Entrepôt de Données de Santé AP-HP Consortium
1 AP-HP Centre, DMU Psychiatrie et Addictologie, Corentin Celton Hospital, Issy-les-Moulineaux, France, 2 Campus de
Somosaguas, Universidad Complutense de Madrid, Pozuelo de Alarcón, Spain, 3 Département de psychiatrie et
d’addictologie, AP-HP, GHU Paris Nord, DMU Neurosciences, Hopital Bichat - Claude Bernard, F-75018 Paris, France,
4 GHU Paris - Psychiatry & Neurosciences, 1 rue Cabanis, 75014 Paris, France, 5 NeuroDiderot, Inserm, FHU I2-D2,
Université de Paris, F-75019 Paris, France, 6 INSERM U1266, Paris, France and 7 Université de Paris, Paris, France
*To whom correspondence should be addressed. Corentin Celton Hospital, AP-HP Centre, Paris University, 4 parvis Corentin Celton; 92130
Issy-les-Moulineaux, France. Email: marinals@ucm.es, Twitter handle: @HoertelN
Submitted 27 November 2021; Revised 10 December 2021; Editorial Decision 14 December 2021; Accepted 14 December 2021
Key words: melatonin, treatment, efficacy, mortality, death, SARS-CoV-2, COVID-19
Melatonin is an hormone secreted from the pineal gland
indicated in the treatment of insomnia and circadian sleep
disturbances.1 In the needed search for an effective treatment for
patients with COVID-19,2 this molecule has been previously proposed as a potential useful treatment against COVID-19 thanks
to its antioxidant, immunomodulatory, anti-inflammatory and
potential SARS-CoV-2 main protease inhibition activities.3–6
However, while a recent randomized clinical trial7 involving
patients hospitalized with mild to moderate COVID-19 suggests
that oral melatonin administration as an adjuvant therapy added
to the standard of care may improve respiratory symptoms and
time of patient discharge vs standard of care alone, another
randomized trial found no substantial improvement in patients
hospitalized for severe COVID-19.8 In this report, we used
data from a multicenter retrospective study involving patients
hospitalized for laboratory-confirmed COVID-19 in Greater
Paris University hospitals, as detailed elsewhere,9 and sought to
examine the association between melatonin use and mortality in
this population. Observational studies examining the potential
usefulness of existing treatments against COVID-19 can be
crucial to help prioritize molecules in clinical trials.
This multicenter observational retrospective cohort study was
conducted at 36 AP-HP hospitals from the beginning of the
epidemic in France, i.e. 24 January 2020, until 31 October 2021,
using data from the AP-HP Health Data Warehouse [‘Entrepôt
de Données de Santé (EDS)’].9,10 We included all adults aged
18 years or over who have been hospitalized in these medical
centers for COVID-19. COVID-19 was ascertained by a positive reverse transcriptase–polymerase chain reaction test from
analysis of nasopharyngeal or oropharyngeal swab specimens.
Data were obtained for demographic characteristics and medical risk factors associated with severe COVID-19, including: sex;
age, categorized into three groups (18–70, 71–80, 81+); hospital,
which was categorized into four classes following the..
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