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..