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Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers

Fernandes et al., Melatonin Research, doi:10.32794/mr11250090
Jan 2021  
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Melatonin for COVID-19
11th treatment shown to reduce risk in December 2020, now with p = 0.0000002 from 18 studies.
Lower risk for mortality, ventilation, and recovery.
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5,100+ studies for 112 treatments. c19early.org
In Silico and rat study showing that higher lung melatonin synthesis (measured by MEL-Index) may predict asymptomatic SARS-CoV-2 carriers through negative correlation with viral entry and infection-related genes. Authors analyzed 288 healthy human lung samples and found that higher MEL-Index scores negatively correlated with expression of genes involved in SARS-CoV-2 infection, including FURIN (spike protein processing) and components of the CD147 receptor complex (viral entry in macrophages). The MEL-Index positively correlated with TMPRSS2, suggesting disrupted viral entry in AT2 epithelial cells when combined with reduced FURIN expression. The study validated MEL-Index as a predictor of lung melatonin content using rat lung tissue samples. Gene set enrichment analysis confirmed negative correlation between MEL-Index and virus-related genes, particularly those involved in mitochondrial function, transcription control, and intracellular trafficking. Authors suggest that high lung melatonin synthesis may provide natural protection against SARS-CoV-2 infection and that nasal melatonin administration could help prevent progression in presymptomatic carriers.
6 preclinical studies support the efficacy of melatonin for COVID-19:
Melatonin may restore altered redox homeostasis in COVID-196, modulates type III interferon responses and reduces inflammatory cytokine production in TLR3 receptor agonist stimulated viral inflammation while preserving tissue integrity3, and negatively regulates genes critical for viral entry in lung tissue, including reduced expression of FURIN and components of the CD147 complex, while potentially disrupting TMPRSS2/ACE2-mediated entry mechanisms2. Melatonin reduces oxidative stress, inhibits NET formation, and protects tissues through anti-inflammatory and antioxidant actions7.
Fernandes et al., 3 Jan 2021, peer-reviewed, 12 authors.
This PaperMelatoninAll
Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19
Alan L Fernandes, Igor H Murai, Bruna Z Reis, Lucas P Sales, Mayara D Santos, Ana J Pinto, Karla F Goessler, Camila Sc Duran, Carla Br Silva, André S Franco, Marina B Macedo, Henrique Hh Dalmolin, Janaina Baggio, Guilherme Gm Balbi, Leila Antonangelo, Valeria F Caparbo, Bruno Gualano, Rosa Mr Pereira
The American Journal of Clinical Nutrition, doi:10.1093/ajcn/nqab426
Background: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. Objectives: We aimed to investigate the effect of a single high dose of vitamin D 3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. Methods: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D 3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1β, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ , granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. Results: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m 2 , of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the betweengroup difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. Conclusions: The findings do not support the use of a single dose of 200,000 IU vitamin D 3 , compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. This trial was registered at clinicaltrials.gov as NCT04449718.
References
Aglipay, Birken, Parkin, Loeb, Thorpe et al., Effect of highdose vs standard-dose wintertime vitamin D supplementation on viral upper respiratory tract infections in young healthy children, JAMA
Al-Bayyari, Hailat, Subih, Alkhalidy, Eaton, Vitamin D 3 reduces risk of cardiovascular and liver diseases by lowering homocysteine levels: double-blinded, randomised, placebo-controlled trial, Br J Nutr
Baggerly, Cuomo, French, Garland, Gorham et al., Sunlight and vitamin D: necessary for public health, J Am Coll Nutr
Bilezikian, Bikle, Hewison, Lazaretti-Castro, Formenti et al., Mechanisms in endocrinology: vitamin D and COVID-19, Eur J Endocrinol
Boulkrane, Ilina, Melchakov, Fedotova, Drago et al., COVID-19 disease and vitamin D: a mini-review, Front Pharmacol
Campbell, Spector, Autophagy induction by vitamin D inhibits both Mycobacterium tuberculosis and human immunodeficiency virus type 1, Autophagy
Christakos, Dhawan, Verstuyf, Verlinden, Carmeliet, Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects, Physiol Rev
De Medeiros Cavalcante, Silva, Costa, Persuhn, Issa et al., Effect of vitamin D3 supplementation and influence of BsmI polymorphism of the VDR gene of the inflammatory profile and oxidative stress in elderly women with vitamin D insufficiency: vitamin D3 megadose reduces inflammatory markers, Exp Gerontol
El Hajj, Walrand, Helou, Yammine, Effect of vitamin D supplementation on inflammatory markers in non-obese Lebanese patients with type 2 diabetes: a randomized controlled trial, Nutrients
Fajgenbaum, June, Cytokine storm, N Engl J Med
Farid, Rola, Koch, Nakhoul, Active vitamin D supplementation and COVID-19 infections: review, Ir J Med Sci
Fiorino, Gallo, Zippi, Sabbatani, Manfredi et al., Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy, Aging Clin Exp Res
Grossmann, Zughaier, Liu, Lyles, Tangpricha, Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation, Eur J Clin Nutr
Heart, Institute, Clinical, Network, Ginde et al., None, N Engl J Med
Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline, J Clin Endocrinol Metab
Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Kalia, Studzinski, Sarkar, Role of vitamin D in regulating COVID-19 severity-an immunological perspective, J Leukocyte Biol
Kearns, Alvarez, Tangpricha, Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review, Endocr Pract
Kloc, Ghobrial, Lipińska-Opałka, Wawrzyniak, Zdanowski et al., Effects of vitamin D on macrophages and myeloid-derived suppressor cells (MDSCs) hyperinflammatory response in the lungs of COVID-19 patients, Cell Immunol
Laplana, Royo, Fibla, Vitamin D Receptor polymorphisms and risk of enveloped virus infection: a meta-analysis, Gene
Lips, Cashman, Lamberg-Allardt, Bischoff-Ferrari, Obermayer-Pietsch et al., Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society, Eur J Endocrinol
Liu, Martins, Lau, Rachmaninoff, Chen et al., Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19, Cell
Liu, Stenger, Li, Wenzel, Tan et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science
Martineau, Forouhi, Vitamin D for COVID-19: a case to answer?, Lancet Diabetes Endocrinol
Mehta, Porter, Manson, Isaacs, Openshaw et al., Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities, Lancet Respir Med
Mitchell, Vitamin-D and COVID-19: do deficient risk a poorer outcome?, Lancet Diabetes Endocrinol
Murai, Fernandes, Sales, Pinto, Goessler et al., Effect of a single high dose of vitamin D 3 on hospital length of stay in patients with moderate to severe COVID-19: a randomized clinical trial, JAMA
Pereira, Damascena, Azevedo, De Almeida Oliveira, Da et al., Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis, Crit Rev Food Sci Nutr, doi:10.1080/10408398.2020.1841090
Rizk, Kalantar-Zadeh, Mehra, Lavie, Rizk et al., Pharmaco-immunomodulatory therapy in COVID-19, Drugs
Schwingshackl, Kimura, Rovnaghi, Saravia, Cormier et al., Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: results from a double-blind, placebo-controlled randomized pilot trial, Cytokine
Seamans, Cashman, Existing and potentially novel functional markers of vitamin D status: a systematic review, Am J Clin Nutr
Shang, Zhao, Hu, Du, Cao, On the use of corticosteroids for 2019-nCoV pneumonia, Lancet
Sinha-Hikim, Duran, Shen, Lee, Friedman et al., Effect of long term vitamin D supplementation on biomarkers of inflammation in Latino and African-American subjects with prediabetes and hypovitaminosis D, Horm Metab Res
Tabatabaeizadeh, Avan, Bahrami, Khodashenas, Esmaeili et al., High dose supplementation of vitamin D affects measures of systemic inflammation: reductions in high sensitivity C-reactive protein level and neutrophil to lymphocyte ratio (NLR) distribution, J Cell Biochem
The, Group, Horby, Lim, Emberson et al., Dexamethasone in hospitalized patients with Covid-19, N Engl J Med
Van Etten, Mathieu, Immunoregulation by 1,25-dihydroxyvitamin D 3 : basic concepts, J Steroid Biochem Mol Biol
Wang, Hu, Hu, Zhu, Liu et al., Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA
Zhou, Fu, Zheng, Wang, Zhao et al., Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients, Natl Sci Rev
Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet
Zhu, Cai, Fan, Lou, Hua et al., Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019, Int J Infect Dis
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Melatonin is synthesized on demand by ' 'immune-competent cells and constitutively by resident macrophages such as alveolar ' 'macrophages. Here we investigated whether the expression of genes relevant to virus invasion ' 'and infection varies according to a genic index (MEL-Index) that estimates the capacity of ' 'the lung to synthesize melatonin. A COVID-19-Signature composed of 455 genes of 288 human ' 'lungs (GTEX, UCSD) was correlated with MEL-Index by Pearson correlation test, gene-set ' 'enrichment analysis, and networking tool that integrates the connectivity between the most ' 'expressed genes, allowing us to compare the same set of genes under different states. The ' 'three independent procedures point to a negative relationship between MEL-Index and ' 'SARS-CoV-2 infection. The entry in epithelial AT2 cells should be hampered by a positive ' 'correlation\xa0TMRPSS2\xa0\xa0and a negative correlation with the coding gene for furin, ' 'suggesting dysfunctional processing in virus spike. Moreover, MEL-Index also negatively ' 'correlates with the genes that codify the proteins of multi-molecular receptor complex CD147, ' 'the gateway in macrophages, and other immune cells. In summary, the perspective that lung and ' 'respiratory tract melatonin could be a natural protective factor opens new epidemiological ' 'and pharmacological perspectives, as high MEL-Index scores could be predictive of ' 'asymptomatic carriers, and nasal administrated melatonin could prevent evolution of ' 'presymptomatic carriers.</jats:p>', 'DOI': '10.32794/mr11250090', 'type': 'journal-article', 'created': {'date-parts': [[2021, 1, 4]], 'date-time': '2021-01-04T02:01:11Z', 'timestamp': 1609725671000}, 'page': '189-205', 'source': 'Crossref', 'is-referenced-by-count': 10, 'title': 'Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and ' 'asymptomatic SARS-CoV-2 carriers', 'prefix': '10.32794', 'volume': '4', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-4323-5614', 'authenticated-orcid': False, 'given': 'Pedro A', 'family': 'Fernandes', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-1676-442X', 'authenticated-orcid': False, 'given': 'Gabriela S', 'family': 'Kinker', 'sequence': 'first', 'affiliation': []}, {'given': 'Bruno V', 'family': 'Navarro', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-9289-4328', 'authenticated-orcid': False, 'given': 'Vinicius C', 'family': 'Jardim', 'sequence': 'first', 'affiliation': []}, {'given': 'Edson D', 'family': 'Ribeiro-Paz', 'sequence': 'first', 'affiliation': []}, {'given': 'Marlina O', 'family': 'Córdoba-Moreno', 'sequence': 'first', 'affiliation': []}, {'given': 'Débora', 'family': 'Santos-Silva', 'sequence': 'first', 'affiliation': []}, {'given': 'Sandra M', 'family': 'Muxel', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-7756-7051', 'authenticated-orcid': False, 'given': 'André', 'family': 'Fujita', 'sequence': 'first', 'affiliation': []}, {'given': 'Carolina Borsoi', 'family': 'Moraes', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-5297-9108', 'authenticated-orcid': False, 'given': 'Helder I', 'family': 'Nakaya', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-5455-8136', 'authenticated-orcid': False, 'given': 'Marcos S', 'family': 'Buckeridge', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-4606-6120', 'authenticated-orcid': False, 'given': 'Regina P', 'family': 'Markus', 'sequence': 'first', 'affiliation': []}], 'member': '18079', 'published-online': {'date-parts': [[2021, 1, 3]]}, 'container-title': 'Melatonin Research', 'original-title': [], 'deposited': { 'date-parts': [[2021, 1, 4]], 'date-time': '2021-01-04T02:01:32Z', 'timestamp': 1609725692000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.melatonin-research.net/index.php/MR/article/view/109'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 1, 3]]}, 'references-count': 0, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2021, 1, 3]]}}, 'URL': 'http://dx.doi.org/10.32794/mr11250090', 'relation': {}, 'ISSN': ['2641-0281'], 'subject': [], 'container-title-short': 'Melatonin Res.', 'published': {'date-parts': [[2021, 1, 3]]}}
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