tetano
Editor, Senior Moderator
J Med Virol
. 2026 Jan;98(1):e70807.
doi: 10.1002/jmv.70807. Oral Melatonin in Critically Ill Patients With COVID-19: A Quasi-Experimental Pragmatic Trial
Miguel Sánchez-García[SUP] 1 2 [/SUP], Jesús A F Tresguerres[SUP] 2 3 [/SUP], Manuel Álvarez-González[SUP] 1 [/SUP], Belén de la Hera[SUP] 1 [/SUP], Virginia Puebla[SUP] 4 [/SUP], Lidia Ybañez[SUP] 4 [/SUP], José-Manuel Martínez-Sesmero[SUP] 4 [/SUP], Antonio Blesa[SUP] 1 [/SUP], Juan-Carlos Martín-Benítez[SUP] 1 [/SUP], Fernando Martínez-Sagasti[SUP] 1 [/SUP], Paloma González-Arenas[SUP] 1 [/SUP], Sara Domingo[SUP] 1 [/SUP], Cándido Pardo[SUP] 1 [/SUP], Silmary Maichle[SUP] 1 [/SUP], Carolina Postigo[SUP] 1 [/SUP], Sara De-Miguel[SUP] 1 [/SUP], María Bringas[SUP] 1 [/SUP], Raquel González-Casanova[SUP] 1 [/SUP], Viktor Yordanov[SUP] 1 [/SUP], Alberto Delgado-Iribarren[SUP] 5 [/SUP], Esther Culebras[SUP] 5 [/SUP], Miguel A Armengol-de la-Hoz[SUP] 6 [/SUP], Antonio Núñez-Reiz[SUP] 1 [/SUP]
Affiliations
Melatonin has demonstrated antioxidant, anti-inflammatory, and potential antiviral properties. Its therapeutic role in critically ill COVID-19 patients admitted to intensive care was underexplored at the start of the pandemic. We conducted a quasi-experimental, pragmatic study over 4 consecutive uninterrupted time periods alternating control groups receiving standard of care (SoC) with treatment groups receiving SoC plus high-dose oral bedtime melatonin (50-200 mg) (OBM). The primary endpoint was 90-day mortality; secondary outcomes included sequential organ failure assessment (SOFA) scores at 4, 7, 14, and 30 days and pre-defined severe adverse events (SAEs). A total of 335 of 339 consecutive patients with a predicted stay > 48 h were enrolled; 202 received OBM with SoC and 133 received SoC alone. OBM was dispensed during the second (n = 162) and fourth (n = 40) study periods after the first (n = 40) and third (n = 93) control group periods, respectively. Melatonin therapy was associated with significantly lower 90-day mortality (20.8% vs. 36.1%, OR 0.46, 95% CI 0.28-0.76). Subjects receiving melatonin had lower SOFA scores on Day 4 and subsequent study visits. SAEs occurred in 84 (41.6%) subjects on OBM and in 80 (60.2%) receiving SoC (risk ratio 0.68, 95% CI 0.54-0.87; p = 0.001). High-dose oral melatonin was safe and associated with improved clinical outcomes. Further evaluation of melatonin and its potential antiviral effects in future epidemics is warranted.
Keywords: COVID‐19; ICU; Oral melatonin; SARS‐CoV‐2; acute respiratory distress syndrome; antiviral effects; mortality.
. 2026 Jan;98(1):e70807.
doi: 10.1002/jmv.70807. Oral Melatonin in Critically Ill Patients With COVID-19: A Quasi-Experimental Pragmatic Trial
Miguel Sánchez-García[SUP] 1 2 [/SUP], Jesús A F Tresguerres[SUP] 2 3 [/SUP], Manuel Álvarez-González[SUP] 1 [/SUP], Belén de la Hera[SUP] 1 [/SUP], Virginia Puebla[SUP] 4 [/SUP], Lidia Ybañez[SUP] 4 [/SUP], José-Manuel Martínez-Sesmero[SUP] 4 [/SUP], Antonio Blesa[SUP] 1 [/SUP], Juan-Carlos Martín-Benítez[SUP] 1 [/SUP], Fernando Martínez-Sagasti[SUP] 1 [/SUP], Paloma González-Arenas[SUP] 1 [/SUP], Sara Domingo[SUP] 1 [/SUP], Cándido Pardo[SUP] 1 [/SUP], Silmary Maichle[SUP] 1 [/SUP], Carolina Postigo[SUP] 1 [/SUP], Sara De-Miguel[SUP] 1 [/SUP], María Bringas[SUP] 1 [/SUP], Raquel González-Casanova[SUP] 1 [/SUP], Viktor Yordanov[SUP] 1 [/SUP], Alberto Delgado-Iribarren[SUP] 5 [/SUP], Esther Culebras[SUP] 5 [/SUP], Miguel A Armengol-de la-Hoz[SUP] 6 [/SUP], Antonio Núñez-Reiz[SUP] 1 [/SUP]
Affiliations
- PMID: 41532840
- DOI: 10.1002/jmv.70807
Melatonin has demonstrated antioxidant, anti-inflammatory, and potential antiviral properties. Its therapeutic role in critically ill COVID-19 patients admitted to intensive care was underexplored at the start of the pandemic. We conducted a quasi-experimental, pragmatic study over 4 consecutive uninterrupted time periods alternating control groups receiving standard of care (SoC) with treatment groups receiving SoC plus high-dose oral bedtime melatonin (50-200 mg) (OBM). The primary endpoint was 90-day mortality; secondary outcomes included sequential organ failure assessment (SOFA) scores at 4, 7, 14, and 30 days and pre-defined severe adverse events (SAEs). A total of 335 of 339 consecutive patients with a predicted stay > 48 h were enrolled; 202 received OBM with SoC and 133 received SoC alone. OBM was dispensed during the second (n = 162) and fourth (n = 40) study periods after the first (n = 40) and third (n = 93) control group periods, respectively. Melatonin therapy was associated with significantly lower 90-day mortality (20.8% vs. 36.1%, OR 0.46, 95% CI 0.28-0.76). Subjects receiving melatonin had lower SOFA scores on Day 4 and subsequent study visits. SAEs occurred in 84 (41.6%) subjects on OBM and in 80 (60.2%) receiving SoC (risk ratio 0.68, 95% CI 0.54-0.87; p = 0.001). High-dose oral melatonin was safe and associated with improved clinical outcomes. Further evaluation of melatonin and its potential antiviral effects in future epidemics is warranted.
Keywords: COVID‐19; ICU; Oral melatonin; SARS‐CoV‐2; acute respiratory distress syndrome; antiviral effects; mortality.