An urgent proposal for the immediate use of melatonin as an adjuvant to anti- SARS-CoV-2 vaccination
Melatonin and anti-SARS-CoV-2 vaccination
Keywords:
COVID-19, Sars-CoV-2, adjuvant, chronobiotic, melatonin, insomnia, immunoenhancement, sleep, vaccination
Abstract
Competition among pharmaceutical companies to develop safe and effective vaccines against SARS-CoV-2 is high. However, based on the prior experience with the influenza vaccine, up to 50% in lack of effectiveness would be found among healthy adults receiving effective vaccines against SARS-CoV-2. There is growing evidence that insufficient sleep may potentially be a pervasive and prominent factor accounting for this variability. Individuals experiencing total or partial sleep loss exhibit markedly reduced antigen-specific antibodies as compared to healthy sleepers. Besides, pre-vaccination sleep quality is also an important contributing factor. Several meta-analyses and expert consensus reports support the view that the chronobiotic/hypnotic properties of melatonin are useful in patients with primary sleep disorders to decrease sleep onset latency and to increase total sleep time. Hence, the prescription of melatonin for at least 2 weeks prior to vaccination can be a useful approach to improve sleep quality and to ensure that the vaccination is performed at a moment of optimal sleep conditions. Moreover, melatonin enhances the immune response to vaccines by increasing peripheral blood CD4+ T cells and IgG-expressing B cells. Administration of exogenous melatonin could increase the potency of the immune response and the duration of the immunity induced by the vaccine. Besides, melatonin could also prevent adverse effects of the vaccination due to its antioxidant and immunomodulatory properties. Therefore, the administration of melatonin from 2 weeks to at least 4 weeks after vaccination may constitute an effective means to enhance the efficacy of vaccination against SARS-CoV-2.
References
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27. Wilson SJ, Nutt DJ, Alford C, Argyropoulos S V., Baldwin DS, Bateson AN, et al. (2010) British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J. Psychopharmacol. 24: 1577–600. https://doi.org/10.1177/0269881110379307.
28. Geoffroy PA, Micoulaud Franchi JA, Lopez R, Schroder CM (2019) The use of melatonin in adult psychiatric disorders: expert recommendations by the French Institute of Medical Research on Sleep (SFRMS). Encephale 45: 413–23. https://doi.org/10.1016/j.encep.2019.04.068.
29. Palagini L, Manni R, Aguglia E, Amore M, Brugnoli R, Girardi P, et al. (2020) Expert opinions and consensus recommendations for the evaluation and management of insomnia in clinical practice: joint statements of five Italian scientific societies. Front. Psychiatry 11: 558. doi: 11. https://doi.org/10.3389/fpsyt.2020.00558.
30. Vecchierini MF, Kilic-Huck U, Quera-Salva MA (2020) Melatonin (MEL) and its use in neurological diseases and insomnia: recommendations of the French Medical and Research Sleep Society (SFRMS). Re.v Neurol. (Paris). https://doi.org/10.1016/j.neurol.2020.06.009.
31. Abbasivash R, Salimi S, Ahsan B, Moallemi N, Sane S (2019) The effect of melatonin on anxiety and pain of tourniquet in intravenous regional anesthesia. Adv. Biomed. Res. 8: 67. https://doi.org/10.4103/abr.abr_106_19.
32. Geoffroy PA, Palagini L (2020) Biological rhythms and chronotherapeutics in depression. Prog. Neuro-Psychopharmacology Biol. Psychiatry 106: 110158. https://doi.org/10.1016/j.pnpbp.2020.110158.
33. Maestroni GJM (1993) The immunoneuroendocrine role of melatonin. J. Pineal Res. 14: 1–10. https://doi.org/10.1111/j.1600-079X.1993.tb00478.x.
34. Cardinali DP, Brusco LI, Selgas L, Esquifino AI (1998) Diurnal rhythms in ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats during Freund’s adjuvant-induced arthritis. Brain Res. 789: 283-92. https://doi.org/10.1016/S0006-8993(98)00015-8.
35. Cardinali DP, Esquifino AI, Srinivasan V, Pandi-Perumal SR (2008) Melatonin and the immune system in aging. Neuroimmunomodulation 15: 272-8. https://doi.org/10.1159/000156470.
36. Castrillón PO, Esquifino AI, Varas A, Zapata A, Cutrera RA, Cardinali DP (2000) Effect of melatonin treatment on 24-h variations in responses to mitogens and lymphocyte subset populations in rat submaxillary lymph nodes. J. Neuroendocrinol. 12: 758-65 https://doi.org/10.1046/j.1365-2826.2000.00519.x.
37. Moreno ACR, Porchia BFMM, Pagni RL, Souza P da C, Pegoraro R, Rodrigues KB, et al. (2018) The combined use of melatonin and an indoleamine 2,3-dioxygenase-1 inhibitor enhances vaccine-induced protective cellular immunity to HPV16-associated tumors. Front. Immunol. 9: 1914. https://doi.org/10.3389/fimmu.2018.01914.
38. Baghban Rahimi S, Mohebbi A, Vakilzadeh G, Biglari P, Razeghi Jahromi S, Mohebi SR, et al. (2018) Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells. Arch. Virol. 163: 587–97. https://doi.org/10.1007/s00705-017-3647-z.
39. Regodón S, Martín-Palomino P, Fernández-Montesinos R, Herrera JL, Carrascosa-Salmoral MP, Píriz S, et al. (2005) The use of melatonin as a vaccine agent. Vaccine 23: 5321–5327. https://doi.org/10.1016/j.vaccine.2005.07.003.
40. Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, et al. (2020) Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 Disease and unexposed individuals. Cell 181: 1489-1501.e15. https://doi.org/10.1016/j.cell.2020.05.015.
41. Carrillo-Vico A, Lardone PJ, Álvarez-Sánchez N, Rodríguez-Rodriguez A, Guerrero JM (2013) Melatonin: buffering the immune system. Int. J. Mol. Sci. 14: 8638–83. https://doi.org/10.3390/ijms14048638.
42. Maestroni G (2020) Exogenous melatonin as potential adjuvant in anti-SarsCov2 vaccines. J. Neuroimmune Pharmacol. 15: 572-573. https://doi.org/10.1007/s11481-020-09956-1.
43. Besag FMC, Vasey MJ, Lao KSJ, Wong ICK (2019) Adverse events associated with melatonin for the treatment of primary or secondary sleep disorders: a systematic review. CNS Drugs 33: 1167–86. https://doi.org/10.1007/s40263-019-00680-w.
44. Andersen LPH, Gögenur I, Rosenberg J, Reiter RJ (2016) The safety of melatonin in humans. Clin. Drug Investig. 36: 169–75. https://doi.org/10.1007/s40261-015-0368-5.
45. Brusco LI, Cruz P, Cangas A V., González Rojas C, Vigo DE, Cardinali DP (2020) Efficacy of melatonin in non-intensive care unit patients with COVID-19 pneumonia and sleep dysregulation. Melatonin Res. 4: 173–88. https://doi.org/10.32794/mr11250089.
2. Besedovsky L, Lange T, Haack M. (2019) The sleep-immune crosstalk in health and disease. Physiol. Rev. 99: 1325–80. https://doi.org/10.1152/physrev.00010.2018.
3. Irwin MR, Opp MR. (2017) Sleep health: reciprocal regulation of sleep and innate immunity. Neuropsychopharmacology 42: 129–55. https://doi.org/10.1038/npp.2016.148.
4. Spiegel K. Effect of sleep deprivation on response to immunization (2002) JAMA J. Am. Med. Assoc. 288: 1471-72. https://doi.org/10.1001/jama.288.12.1471-a.
5. Lange T, Perras B, Fehm HL, Born J. (2003) Sleep enhances the human antibody response to hepatitis A vaccination. Psychosom. Med. 65: 831–5. https://doi.org/10.1097/01.PSY.0000091382.61178.F1.
6. Lange T, Dimitrov S, Bollinger T, Diekelmann S, Born J. (2011) Sleep after vaccination boosts immunological memory. J. Immunol. 187: 283–90. https://doi.org/10.4049/jimmunol.1100015.
7. Prather AA, Hall M, Fury JM, Ross DC, Muldoon MF, Cohen S, et al. (2012) Sleep and antibody response to hepatitis B vaccination. Sleep 35: 1063–9. https://doi.org/10.5665/sleep.1990.
8. Ayling K, Fairclough L, Tighe P, Todd I, Halliday V, Garibaldi J, et al. (2018) Positive mood on the day of influenza vaccination predicts vaccine effectiveness: A prospective observational cohort study. Brain. Behav. Immun. 67: 314–23. https://doi.org/10.1016/j.bbi.2017.09.008.
9. Dopp JM, Wiegert NA, Moran JJ, Muller D, Weber S, Hayney MS. (2007) Humoral immune responses to influenza vaccination in patients with obstructive sleep apnea. Pharmacotherapy 27: 1483–9. https://doi.org/10.1592/phco.27.11.1483.
10. Ruiz FS, Rosa DS, Zimberg IZ, dos Santos Quaresma MV, Nunes JO, Apostolico JS, et al. (2020) Night shift work and immune response to the meningococcal conjugate vaccine in healthy workers: a proof of concept study. Sleep Med. 75: 263–75. https://doi.org/10.1016/j.sleep.2020.05.032.
11. Prather AA, Pressman SD, Miller GE, Cohen S. (2020) Temporal links between self-reported sleep and antibody responses to the influenza vaccine. Int. J. Behav. Med. https://doi.org/10.1007/s12529-020-09879-4.
12. Larenas-Linnemann D, Rodríguez-Pérez N, Arias-Cruz A, Blandón-Vijil MV, Del Río-Navarro BE, Estrada-Cardona A, et al. (2020) Enhancing innate immunity against virus in times of COVID-19: Trying to untangle facts from fictions. World Allergy Organ. J. 13. https://doi.org/10.1016/j.waojou.2020.100476.
13. Cardinali DP, Brown GM, Pandi-Perumal SR. Can Melatonin be a potential “silver bullet” in treating COVID-19 patients? (2020) Diseases 8: 44. https://doi.org/10.3390/diseases8040044.
14. Dawson D, Armstrong SM. (1996) Chronobiotics - Drugs that shift rhythms. Pharmacol. Ther. 69: 15–36. https://doi.org/10.1016/0163-7258(95)02020-9.
15. Lewy A, Emens J, Jackman A, Yuhas K. (2006) Circadian uses of melatonin in humans. Chronobiol. Int. 23: 403–12. https://doi.org/10.1080/07420520500545862.
16. Gulia KK, Kumar VM. (2020) Importance of sleep for health and wellbeing amidst COVID-19 pandemic. Sleep Vigil. 4: 49–50. https://doi.org/10.1007/s41782-020-00087-4.
17. Jawaid A. (2020) Protecting older adults during social distancing. Science 80- 368: 145. https://doi.org/10.1126/science.abb7885.
18. Zaki NFW, Spence DW, BaHammam AS, Pandi-Perumal SR, Cardinali DP, Brown GM (2018) Chronobiological theories of mood disorder. Eur. Arch. Psychiatry Clin. Neurosci. 268: (2):107-118. https://doi.org/10.1007/s00406-017-0835-5.
19. Cardinali DP, Brown GM, Reiter RJ, Pandi-Perumal SR (2020) Elderly as a high-risk group during COVID-19 pandemic: effect of circadian misalignment, sleep dysregulation and melatonin administration. Sleep Vigil. 4: 81–87. https://doi.org/10.1007/s41782-020-00111-7.
20. Lewy A (2010) Clinical implications of the melatonin phase response curve. J. Clin. Endocrinol. Metab. 95: 3158–60. https://doi.org/10.1210/jc.2010-1031.
21. Skene DJ, Arendt J (2007) Circadian rhythm sleep disorders in the blind and their treatment with melatonin. Sleep Med. 8: 651–5. https://doi.org/10.1016/j.sleep.2006.11.013.
22. Arendt J (2018) Approaches to the pharmacological management of jet lag. Drugs 78: 1419–31. https://doi.org/10.1007/s40265-018-0973-8.
23. Burgess HJ, Emens JS (2018) Drugs used in circadian sleep-wake rhythm disturbances. Sleep Med. Clin. 13: 231–41. https://doi.org/10.1016/j.jsmc.2018.02.006.
24. Ferracioli-Oda E, Qawasmi A, Bloch MH (2013) Meta-Analysis: melatonin for the treatment of primary sleep disorders. PLoS One 8 (5): e63773. https://doi.org/10.1371/journal.pone.0063773.
25. Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL (2017) Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep Med. Rev. 34: 10–22. https://doi.org/10.1016/j.smrv.2016.06.005.
26. Li T, Jiang S, Han M, Yang Z, Lv J, Deng C, et al. (2019) Exogenous melatonin as a treatment for secondary sleep disorders: a systematic review and meta-analysis. Front. Neuroendocrinol. 52: 22–8. https://doi.org/10.1016/j.yfrne.2018.06.004.
27. Wilson SJ, Nutt DJ, Alford C, Argyropoulos S V., Baldwin DS, Bateson AN, et al. (2010) British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J. Psychopharmacol. 24: 1577–600. https://doi.org/10.1177/0269881110379307.
28. Geoffroy PA, Micoulaud Franchi JA, Lopez R, Schroder CM (2019) The use of melatonin in adult psychiatric disorders: expert recommendations by the French Institute of Medical Research on Sleep (SFRMS). Encephale 45: 413–23. https://doi.org/10.1016/j.encep.2019.04.068.
29. Palagini L, Manni R, Aguglia E, Amore M, Brugnoli R, Girardi P, et al. (2020) Expert opinions and consensus recommendations for the evaluation and management of insomnia in clinical practice: joint statements of five Italian scientific societies. Front. Psychiatry 11: 558. doi: 11. https://doi.org/10.3389/fpsyt.2020.00558.
30. Vecchierini MF, Kilic-Huck U, Quera-Salva MA (2020) Melatonin (MEL) and its use in neurological diseases and insomnia: recommendations of the French Medical and Research Sleep Society (SFRMS). Re.v Neurol. (Paris). https://doi.org/10.1016/j.neurol.2020.06.009.
31. Abbasivash R, Salimi S, Ahsan B, Moallemi N, Sane S (2019) The effect of melatonin on anxiety and pain of tourniquet in intravenous regional anesthesia. Adv. Biomed. Res. 8: 67. https://doi.org/10.4103/abr.abr_106_19.
32. Geoffroy PA, Palagini L (2020) Biological rhythms and chronotherapeutics in depression. Prog. Neuro-Psychopharmacology Biol. Psychiatry 106: 110158. https://doi.org/10.1016/j.pnpbp.2020.110158.
33. Maestroni GJM (1993) The immunoneuroendocrine role of melatonin. J. Pineal Res. 14: 1–10. https://doi.org/10.1111/j.1600-079X.1993.tb00478.x.
34. Cardinali DP, Brusco LI, Selgas L, Esquifino AI (1998) Diurnal rhythms in ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats during Freund’s adjuvant-induced arthritis. Brain Res. 789: 283-92. https://doi.org/10.1016/S0006-8993(98)00015-8.
35. Cardinali DP, Esquifino AI, Srinivasan V, Pandi-Perumal SR (2008) Melatonin and the immune system in aging. Neuroimmunomodulation 15: 272-8. https://doi.org/10.1159/000156470.
36. Castrillón PO, Esquifino AI, Varas A, Zapata A, Cutrera RA, Cardinali DP (2000) Effect of melatonin treatment on 24-h variations in responses to mitogens and lymphocyte subset populations in rat submaxillary lymph nodes. J. Neuroendocrinol. 12: 758-65 https://doi.org/10.1046/j.1365-2826.2000.00519.x.
37. Moreno ACR, Porchia BFMM, Pagni RL, Souza P da C, Pegoraro R, Rodrigues KB, et al. (2018) The combined use of melatonin and an indoleamine 2,3-dioxygenase-1 inhibitor enhances vaccine-induced protective cellular immunity to HPV16-associated tumors. Front. Immunol. 9: 1914. https://doi.org/10.3389/fimmu.2018.01914.
38. Baghban Rahimi S, Mohebbi A, Vakilzadeh G, Biglari P, Razeghi Jahromi S, Mohebi SR, et al. (2018) Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells. Arch. Virol. 163: 587–97. https://doi.org/10.1007/s00705-017-3647-z.
39. Regodón S, Martín-Palomino P, Fernández-Montesinos R, Herrera JL, Carrascosa-Salmoral MP, Píriz S, et al. (2005) The use of melatonin as a vaccine agent. Vaccine 23: 5321–5327. https://doi.org/10.1016/j.vaccine.2005.07.003.
40. Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, et al. (2020) Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 Disease and unexposed individuals. Cell 181: 1489-1501.e15. https://doi.org/10.1016/j.cell.2020.05.015.
41. Carrillo-Vico A, Lardone PJ, Álvarez-Sánchez N, Rodríguez-Rodriguez A, Guerrero JM (2013) Melatonin: buffering the immune system. Int. J. Mol. Sci. 14: 8638–83. https://doi.org/10.3390/ijms14048638.
42. Maestroni G (2020) Exogenous melatonin as potential adjuvant in anti-SarsCov2 vaccines. J. Neuroimmune Pharmacol. 15: 572-573. https://doi.org/10.1007/s11481-020-09956-1.
43. Besag FMC, Vasey MJ, Lao KSJ, Wong ICK (2019) Adverse events associated with melatonin for the treatment of primary or secondary sleep disorders: a systematic review. CNS Drugs 33: 1167–86. https://doi.org/10.1007/s40263-019-00680-w.
44. Andersen LPH, Gögenur I, Rosenberg J, Reiter RJ (2016) The safety of melatonin in humans. Clin. Drug Investig. 36: 169–75. https://doi.org/10.1007/s40261-015-0368-5.
45. Brusco LI, Cruz P, Cangas A V., González Rojas C, Vigo DE, Cardinali DP (2020) Efficacy of melatonin in non-intensive care unit patients with COVID-19 pneumonia and sleep dysregulation. Melatonin Res. 4: 173–88. https://doi.org/10.32794/mr11250089.
Published
2021-01-03
How to Cite
[1]
Cardinali, D.P., Brown, G.M. and Pandi-Perumal, S.R. 2021. An urgent proposal for the immediate use of melatonin as an adjuvant to anti- SARS-CoV-2 vaccination. Melatonin Research. 4, 1 (Jan. 2021), 206-212. DOI:https://doi.org/https://doi.org/10.32794/mr11250091.
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