COVID fought by Vitamin D as well as both mild and intense exercise
Influence of exercise and vitamin D on the immune system against Covid-19: an integrative review of current literature
Mol Cell Biochem. 2022 Mar 8. doi: 10.1007/s11010-022-04402-7
Matheus Ribeiro Bizuti 1, Édina Starck 1, Kimberly Kamila da Silva Fagundes 1, Josiano Guilherme Puhle 2, Lucas Medeiros Lima 1, Natan Rodrigues de Oliveira 1, Guilherme Vinicio de Sousa Silva 1, Débora Tavares Resende E Silva 3

Respiratory infections of viral origin have become the leading cause of infectious diseases in the world. In 2020, the World Health Organization (WHO) declared a pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Coronavirus Disease 2019 (Covid-19). The pandemic caused by the new coronavirus has challenged the entire global health system, since Covid-19 has a high rate of morbidity and mortality. The immune response to the virus depends on factors such as age, genetics, nutritional status, physical status, as well as environmental factors. Despite scientific advances, so far, there is still no specific therapy for the disease. Thus, this study aims to analyze the contribution of physical exercise and maintenance and/or supplementation of vitamin D to the strengthening of the immune system against viral infections, among them, Covid-19. Regular practice of moderate-intensity physical activity is responsible for promoting a reduction in the concentrations of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β), as well as triggering the increase in the production of anti-inflammatory cytokines (IL-4 and IL-10). In addition, hypovitaminosis D predisposes to the development of chronic diseases and infections. Therefore, in patients affected by Covid-19, the maintenance of vitamin D levels contributes significantly to the 0prevention of the cytokine storm. Thus, the association between maintaining vitamin D levels and performing moderate-intensity physical exercise is responsible for strengthening the immune system and, therefore, triggering a defense mechanism against infections by intracellular microorganisms, in which SARS -CoV-2.
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References
Dhama K, Khan S, Tiwari R et al (2020) Coronavirus disease 2019–COVID-19. Clin Microbiol Rev 33:e00028-e120. https://doi.org/10.1128/cmr.00028-20 - DOI - PubMed - PMC
Machhi J, Herskovitz J, Senan AM et al (2020) The natural history, pathobiology, and clinical manifestations of SARS-CoV-2 infections. J Neuroimmune Pharmacol 21:1–28. https://doi.org/10.1007/s11481-020-09944-5 - DOI
da Silveira MP, Fagundes KKS, Bizuti MR et al (2020) Physical exercise as a tool to help the immune system against covid-19: an integrative review of the current literature. Clin Exp Med 21:15–28. https://doi.org/10.1007/s10238-020-00650-3 - DOI - PubMed
Muralidar S, Ambi SV, Sekaran S et al (2020) The emergence of COVID-19 as a global pandemic: understanding the epidemiology, immune response and potential therapeutic targets of SARS-CoV-2. Biochimie 179:85–100. https://doi.org/10.1016/j.biochi.2020.09.018 - DOI - PubMed - PMC
Chandran M, Maung AC, Mithal A et al (2020) Vitamin D in COVID - 19: Dousing the fire or averting the storm?—A perspective from the Asia-Pacific. Osteoporos Sarcopenia 6:97–105. https://doi.org/10.1016/j.afos.2020.07.003 - DOI - PubMed - PMC
Ali N (2020) Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health 13:1373–1380. https://doi.org/10.1016/j.jiph.2020.06.021 - DOI - PubMed - PMC
Charoenngam N, Holick MF (2020) Immunologic effects of vitamin D on human health and disease. Nutrients 12:2097. https://doi.org/10.3390/nu12072097 - DOI - PMC
Marques CDL, Dantas AT, Fragoso TS et al (2010) The importance of vitamin D levels in autoimmune diseases. Braz J Rheumatol 50:67–80. https://doi.org/10.1590/S0482-50042010000100007 - DOI
Yang P-H, Ding Y-B, Xu Z et al (2020) Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19. Infect Dis Poverty 9:161. https://doi.org/10.1186/s40249-020-00780-6 - DOI - PubMed - PMC
Zumla A, Hui DS, Azhar EI et al (2020) Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet 395:e35–e36. https://doi.org/10.1016/S0140-6736(20)30305-6 - DOI - PubMed - PMC
Sousa FH, Casanova V, Findlay F et al (2017) Cathelicidins display conserved direct antiviral activity towards rhinovirus. Peptides 95:76–83. https://doi.org/10.1016/j.peptides.2017.07.013 - DOI - PubMed - PMC
Barlow PG, Svoboda P, Mackellar A et al (2011) Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37. PLoS ONE 6:e25333. https://doi.org/10.1371/journal.pone.0025333 - DOI - PubMed - PMC
Tripathi S, Tecle T, Verma A et al (2013) The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins. J Gen Virol 94:40–49. https://doi.org/10.1099/vir.0.045013-0 - DOI - PubMed - PMC
Rawson ES, Miles MP, Larson-Meyer DE (2018) Dietary supplements for health, adaptation, and recovery in athletes. Int J Sport Nutr Exerc Metab 28:188–199. https://doi.org/10.1123/ijsnem.2017-0340 - DOI - PubMed
He CS, Fraser WD, Tang J et al (2016) The effect of 14 weeks of vitamin D 3 supplementation on antimicrobial peptides and proteins in athletes. J Sports Sci 34:67–74. https://doi.org/10.1080/02640414.2015.1033642 - DOI - PubMed
Pastuszak-Lewandoska D, Domańska-Senderowska D, Kiszałkiewicz J et al (2020) Expression levels of selected cytokines and microRNAs in response to vitamin D supplementation in ultra-marathon runners. Eur J Sport Sci 20:219–228. https://doi.org/10.1080/17461391.2019.1635649 - DOI - PubMed
Terra R, da Silva SAG, Pinto VS et al (2012) Effect of exercise on immune system: response, adaptation and cell signaling. Revista Brasileira de Medicina do Esporte 18:208–214. https://doi.org/10.1590/S1517-86922012000300015 - DOI
El-kader SMA, Al-Shreef FM (2018) Inflammatory cytokines and immune system modulation by aerobic versus resisted exercise training for elderly. Afr Health Sci 18:120–131. https://doi.org/10.4314/ahs.v18i1.16 - DOI
Paolucci EM, Loukov D, Bowdish DME et al (2018) exercise reduces depression and inflammation but intensity matters. Biol Psychol 133:79–84. https://doi.org/10.1016/j.biopsycho.2018.01.015 - DOI - PubMed
Ferreira GA, Felippe LC, Bertuzzi R et al (2018) The effects of acute and chronic sprint-interval training on cytokine responses are independent of prior caffeine intake. Front Physiol 9:671. https://doi.org/10.3389/fphys.2018.00671 - DOI - PubMed - PMC
Senna SM, Torres MK, Lopes DA et al (2016) Moderate physical training attenuates perinatal low-protein-induced spleen lymphocyte apoptosis in endotoxemic adult offspring rats. Eur J Nutr 55:1113–1122. https://doi.org/10.1007/s00394-015-0925-y - DOI - PubMed
Bigley AB, Rezvani K, Pistillo M et al (2015) Acute exercise preferentially redeploys NK-cells with a highly differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells. Part II: impact of latent cytomegalovirus infection and catecholamine sensitivity. Brain Behav Immun 49:59–65. https://doi.org/10.1016/j.bbi.2014.12.027 - DOI - PubMed
Sellami M, Gasmi M, Denham J et al (2018) Effects of acute and chronic exercise on immunological parameters in the elderly aged: can physical activity counteract the effects of aging? Front Immunol 9:2187. https://doi.org/10.3389/fimmu.2018.02187 - DOI - PubMed - PMC
Simpson RJ, Kunz H, Agha N et al (2015) exercise and the regulation of immune functions. Prog Mol Biol Transl Sci 135:355–379. https://doi.org/10.1016/bs.pmbts.2015.08.001 - DOI - PubMed
Leandro CG, Silva WTF, Lima-Silva AE (2020) Covid-19 and exercise -induced immunomodulation. NeuroImmunoModulation 27:75–78. https://doi.org/10.1159/000508951 - DOI - PubMed
Jamilloux Y, Gerfaud-Valentin M, Sève P (2020) Intravenous anakinra for cytokine storm syndromes. Lancet Rheumatol 2:E521–E522. https://doi.org/10.1016/S2665-9913(20)30225-3 - DOI - PubMed - PMC
Mehta P, Porter JC, Manson JJ et al (2020) Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities. Lancet Respir Med 8:822–830. https://doi.org/10.1016/S2213-2600(20)30267-8 - DOI - PubMed - PMC
Svensson M, Lexell J, Deierborg T (2015) Effects of physical exercise on neuroinflammation, neuroplasticity, neurodegeneration, and behavior. Neurorehabil Neural Repair 29:577–589. https://doi.org/10.1177/1545968314562108 - DOI - PubMed
Steensberg A, Fischer CP, Keller C et al (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Metab 285:E433–E437. https://doi.org/10.1152/ajpendo.00074.2003 - DOI
Scheffer DL, Latini A (2020) exercise -induced immune system response: anti-inflammatory status on peripheral and central organs. Biochim Biophys Acta Mol Basis Dis 1866:165823. https://doi.org/10.1016/j.bbadis.2020.165823 - DOI - PubMed - PMC
Fischer CP (2006) Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 12:6–33 - PubMed
Wedell-Neergaard AS, Lang Lehrskov L, Christensen RH et al (2019) exercise -induced changes in visceral adipose tissue mass are regulated by IL-6 signaling: a randomized controlled trial. Cell Metab 29:844–855. https://doi.org/10.1016/j.cmet.2018.12.007 - DOI - PubMed
Pedersen BK (2017) Anti-inflammatory effects of exercise : role in diabetes and cardiovascular disease. Eur J Clin Investig 47:600–611. https://doi.org/10.1111/eci.12781 - DOI
Kamen DL, Tangpricha V (2010) Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med 88:441–450. https://doi.org/10.1007/s00109-010-0590-9 - DOI - PubMed
White JH (2012) Vitamin D metabolism and signaling in the immune system. Rev Endocr Metab Disord 13:21–29. https://doi.org/10.1007/s11154-011-9195-z - DOI - PubMed
Martineau AR, Jolliffe DA, Hooper RL et al (2017) Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 356:i6583. https://doi.org/10.1136/bmj.i6583 - DOI - PubMed - PMC
Gonçalves TJM, Gonçalves SEAB, Guarnieri A et al (2020) Prevalence of obesity and hypovitaminosis D in elderly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Nutr ESPEN 40:110–114. https://doi.org/10.1016/j.clnesp.2020.10.008 - DOI - PubMed - PMC
Laird E, Rhodes J, Kenny RA (2020) Vitamin D and inflammation: potential implications for severity of Covid-19. Ir Med J 113:81 - PubMed
Merzon E, Tworowski D, Gorohovski A et al (2020) Low plasma 25 (OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. FEBS J 287:3693–3702. https://doi.org/10.1111/febs.15495 - DOI - PubMed
Liu PT, Stenger S, Li H et al (2006) Toll-like receptor triggering of a vitamin D -mediated human antimicrobial response. Science 311:1773–1783. https://doi.org/10.1126/science.1123933 - DOI
Xu J, Yang J, Chen J et al (2017) Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol Med Rep 2017:7432–7438. https://doi.org/10.3892/mmr.2017.7546 - DOI
Bae M, Kim H (2020) The role of Vitamin C, Vitamin D , and selenium in immune system against COVID-19. Molecules 25:5346. https://doi.org/10.3390/moléculas25225346 - DOI - PubMed - PMC
Campbell PA, Young MW, Lee RC (2020) Vitamin D clinical pharmacology: relevance to COVID-19 pathogenesis. J Natl Med Assoc. https://doi.org/10.1016/j.jnma.2020.09.152 - DOI - PubMed
Mora RJ, Iwata M, von Andrian UH (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8:685–698. https://doi.org/10.1038/nri2378 - DOI - PubMed - PMC
Prietl B, Treiber G, Pieber T et al (2013) Vitamin D and immune function. Nutrients 5:2502–2521. https://doi.org/10.3390/nu5072502 - DOI - PubMed - PMC
Kumar R, Rathi H, Haq A et al (2021) Putative roles of vitamin D in modulating immune response and immunopathology associated with COVID-19. Virus Res 292:198235. https://doi.org/10.1016/j.virusres.2020.198235 - DOI - PubMed
Cantorna MT, Snyder L, Lin YD et al (2015) Vitamin D and 1,25(OH)2D regulation of T cells. Nutrients 7:3011–3021. https://doi.org/10.3390/nu7043011 - DOI - PubMed - PMC
Chatterjee S, Sengupta T, Majumder S et al (2020) COVID-19: a probable role of the anticoagulant Protein S in managing COVID-19-associated coagulopathy. Aging 12:15954–15961. https://doi.org/10.18632/aging.103869 - DOI - PubMed - PMC
Ali MAM, Spinler AS (2021) COVID-19 and thrombosis: from bench to bedside. Trends Cardiovasc Med 31:143–160. https://doi.org/10.1016/j.tcm.2020.12.004 - DOI - PubMed
Sengupta T, Majumder R, Majumder S (2021) Role of vitamin D in treating COVID-19-associated coagulopathy: problems and perspectives. Mol Cell Biochem 476:2421–2427. https://doi.org/10.1007/s11010-021-04093-6 - DOI - PubMed - PMC
Meehan M, Penckofer S (2014) The role of vitamin D in the aging adult. J Aging Gerontol 2:60–71. https://doi.org/10.12974/2309-6128.2014.02.02.1 - DOI - PubMed - PMC
Abraham J, Dowling K, Florentine S (2021) Can optimum solar radiation exposure or supplemented vitamin D intake reduce the severity of COVID-19 symptoms? Int J Environ Res Public Health 18:740. https://doi.org/10.3390/ijerph18020740 - DOI - PMC
Bilezikian JP, Bikle D, Hewison M et al (2020) Mechanisms in endocrinology: vitamin D and COVID-19. Eur J Endocrinol 183:R133–R147. https://doi.org/10.1530/EJE-20-0665 - DOI - PubMed
Machado PRL, Araújo MLAB, Carvalho L et al (2004) Mecanismos de resposta imune às infecções. An Bras Dermatol 79:647–662. https://doi.org/10.1590/S0365-05962004000600002 - DOI
Aranow C (2011) Vitamin D and the immune system. J Investig Med 59:881–886. https://doi.org/10.2310/JIM.0b013e31821b8755 - DOI - PubMed - PMC
Adams JS, Ren S, Liu PT et al (2009) Vitamin D -directed rheostatic regulation of monocyte antibacterial responses. J Immunol 182:4289–4295. https://doi.org/10.4049/jimmunol.0803736 - DOI - PubMed
Charoenngam N, Shirvani A, Holick MF (2021) Vitamin D and Its Potential Benefit for the COVID-19 Pandemic. Endocr Pract 27:484–493. https://doi.org/10.1016/j.eprac.2021.03.006 - DOI - PubMed - PMC
Uberti F, Lattuada D, Morsanuto V et al (2014) Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways. J Clin Endocrinol Metab 99:1367–1374. https://doi.org/10.1210/jc.2013-2103 - DOI - PubMed
Todd JJ, McSorley EM, Madigan SM et al (2017) Oral spray wintertime vitamin D 3 supplementation has no impact on inflammation in Gaelic footballers. Scand J Med Sci Sports 27:1300–1307. https://doi.org/10.1111/sms.12785 - DOI - PubMed
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252. https://doi.org/10.1038/32588 - DOI
Dickie LJ, Church LD, Coulthard LR et al (2010) Vitamin D 3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes. Rheumatology 49:1466–1471. https://doi.org/10.1093/rheumatology/keq124 - DOI - PubMed
Jevalikar G, Mithal A, Singh A et al (2021) Lack of association of baseline 25-hydroxy vitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19. Sci Rep 11:6258. https://doi.org/10.1038/s41598-021-85809-y - DOI - PubMed - PMC
Güven M, Gültekin H (2021) The effect of high-dose parenteral vitamin D 3 on COVID-19-related inhospital mortality in critical COVID-19 patients during intensive care unit admission: an observational cohort study. Eur J Clin Nutr. https://doi.org/10.1038/s41430-021-00984-5 - DOI - PubMed - PMC
Jain A, Chaurasia R, Sengar NS et al (2020) Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep 10:20191. https://doi.org/10.1038/s41598-020-77093-z - DOI - PubMed - PMC
Bobart LF, Dietrich MA, Johannsen N et al (2017) Emerging relationships between vitamin D status, physical activity habits, and immune indices in college-aged females. Int J Vitam Nutr Res 87:49–58. https://doi.org/10.1024/0300-9831/a000424 - DOI
Mercola J, Grant WB, Wagner CL (2020) Evidence regarding vitamin D and risk of COVID-19 and its severity. Nutrients 12:3361. https://doi.org/10.3390/nu12113361 - DOI - PMC
Grant WB, Lahore H , Rockwell MS (2020) The benefits of vitamin D supplementation for athletes: better performance and reduced risk of COVID-19. Nutrients 12:3741. https://doi.org/10.3390/nu12123741 - DOI - PMC
Yang YC, Chou CL, Kao CL (2020) exercise , nutrition, and medication considerations in the light of the COVID pandemic, with specific focus on geriatric population: a literature review. J Chin Med Assoc 83:977–980. https://doi.org/10.1097/JCMA.0000000000000393 - DOI - PubMed - PMC
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