Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial
Pierachille Santus, Michela Sabbatucci, Irene García-García, Enrique Seco-Meseguer, Pilar Ruiz-Seco, Ge Navarro-Jimenez, Raúl Martínez-Porqueras, María Espinosa-Díaz, Juan José Orte-Albás, Iñigo Sagastagoit, María Teresa García-Morales, María Jiménez-González, Lucía Martínez De Soto, Ana Isabel Bajo-Martínez, María Del Palacio-Tamarit, Raquel López-García, Lucía Díaz-García, Javier Queiruga-Parada, Christi Giesen, Ana Pérez-Ville, Marta De Castro-Martínez, Juan J González-García, Miguel Rodriguez-Rubio, Pedro De La Oliva, José R Arribas, Antonio J Carcas, Alberto M Borobia
We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: The authors declare no conflict of interest.
References
Abella, Jolkovsky, Biney, Uspal, Hyman et al., Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial, JAMA Intern. Med,
doi:10.1001/jamainternmed.2020.6319Acuña-Castroviejo, Escames, Figueira, De, Oliva et al., Clinical trial to test the efficacy of melatonin in COVID-19, J. Pineal Res,
doi:10.1111/jpi.12683Alavian, Kolahdouzan, Mortezazadeh, Dds, Antiretrovirals for Prophylaxis Against COVID-19: A Comprehensive Literature Review, J. Clin. Pharmacol,
doi:10.1002/jcph.1788Anderson, Maes, Markus, Rodriguez, Ebola virus: Melatonin as a readily available treatment option, J. Med. Virol,
doi:10.1002/jmv.24130Ayerdi, Puerta, Clavo, Vera, Ballesteros et al., Preventive Efficacy of Tenofovir/Emtricitabine Against Severe Acute Respiratory Syndrome Coronavirus 2 Among Pre-Exposure Prophylaxis Users, Open Forum Infect. Dis,
doi:10.1093/ofid/ofaa455Ben-Zvi, Kivity, Langevitz, Shoenfeld, Hydroxychloroquine: From Malaria to Autoimmunity, Clin. Rev. Allergy Immunol,
doi:10.1007/s12016-010-8243-xBoga, Coto-Montes, Rosales-Corral, Tan, Reiter, Beneficial actions of melatonin in the management of viral infections: A new use for this "molecular handyman, Rev. Med. Virol,
doi:10.1002/rmv.1714Castilla, Guevara, Miqueleiz, Baigorria, Ibero-Esparza et al., Risk Factors of Infection, Hospitalization and Death from SARS-CoV-2: A Population-Based Cohort Study, J. Clin. Med,
doi:10.3390/jcm10122608Cipolla-Neto, Amaral, Afeche, Tan, Reiter, Melatonin, energy metabolism, and obesity: A review, J. Pineal Res,
doi:10.1111/jpi.12137Clinicaltrials, gov Daily Regimen of Tenofovir/Emtricitabine as Prevention for COVID-19 in Health Care Personnel in Colombia
Clinicaltrials, gov Randomized Clinical Trial for the Prevention of SARS-CoV-2 Infection (COVID-19) in Healthcare Personnel
Clinicaltrials, gov TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study
Cruciani, Pati, Masiello, Malena, Pupella et al., Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis, Correction in Diagnostics,
doi:10.3390/diagnostics11091645De Wit, Feldmann, Cronin, Jordan, Okumura et al., Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection,
doi:10.1073/pnas.1922083117Del Amo, Polo, Moreno, Diaz-Brito, Martínez et al., Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy: A Cohort Study, Ann. Intern. Med
Favero, Franceschetti, Bonomini, Rodella, Rezzani, Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation, Int. J. Endocrinol,
doi:10.1155/2017/1835195García, Rubio, Mariblanca, De Soto, García et al., A randomized multicenter clinical trial to evaluate the efficacy of melatonin in the prophylaxis of SARS-CoV-2 infection in high-risk contacts (MeCOVID Trial): A structured summary of a study protocol for a randomised controlled trial, Trials,
doi:10.1186/s13063-020-04436-6Gunn, Middleton, Davies, Revell, Skene, Sex differences in the circadian profiles of melatonin and cortisol in plasma and urine matrices under constant routine conditions, Chronobiol. Int,
doi:10.3109/07420528.2015.1112396Malin, Suárez, Priesner, Fätkenheuer, Rybniker, Remdesivir against COVID-19 and Other Viral Diseases, Clin. Microbiol. Rev,
doi:10.1128/CMR.00162-20Nainu, Abidin, Bahar, Frediansyah, Bin Emran et al., SARS-CoV-2 reinfection and implications for vaccine development, Hum. Vaccines Immunother,
doi:10.1080/21645515.2020.1830683Preparation, -M.; Writing-Review, Supervision, None
Rajasingham, Bangdiwala, Nicol, Skipper, Pastick et al., Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial, Clin. Infect. Dis,
doi:10.1093/cid/ciaa1571Reiter, Mayo, Tan, Sainz, Alatorre-Jimenez et al., Melatonin as an antioxidant: Under promises but over delivers, J. Pineal Res,
doi:10.1111/jpi.12360Rodríguez-Rubio, Figueira, Acuña-Castroviejo, Borobia, Escames et al., A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in patients with COVID-19 admitted to the intensive care unit (MelCOVID study): A structured summary of a study protocol for a randomized controlled trial, Trials,
doi:10.1186/s13063-020-04632-4Shiu, Reiter, Tan, Pang, Urgent search for safe and effective treatments of severe acute respiratory syndrome: Is melatonin a promising candidate drug?, J. Pineal Res,
doi:10.1034/j.1600-079X.2003.00068.xSingh, Chauhan, Kakkar, Hydroxychloroquine for the treatment and prophylaxis of COVID-19: The journey so far and the road ahead, Eur. J. Pharmacol,
doi:10.1016/j.ejphar.2020.173717Sreepadmanabh, Sahu, Chande, COVID-19: Advances in diagnostic tools, treatment strategies, and vaccine development, J. Biosci,
doi:10.1007/s12038-020-00114-6Who, Coronavirus Disease
Álvez, SARS-CoV2 coronavirus: So far polite with children. Debatable immunological and non-immunological evidence, Allergol. Immunopathol,
doi:10.1016/j.aller.2020.05.003
