Vitamin D Levels in COVID-19 Outpatients from Western Mexico: Clinical Correlation and Effect of Its Supplementation
Gabriela Athziri Sánchez-Zuno, Guillermo González-Estevez, Mónica Guadalupe Matuz-Flores, Gabriela Macedo-Ojeda, Jorge Hernández-Bello, Jesús Carlos Mora-Mora, Edsaúl Emilio Pérez-Guerrero, Mariel García-Chagollán, Natali Vega-Magaña, Francisco Javier Turrubiates-Hernández, Andrea Carolina Machado-Sulbaran, José Francisco Muñoz-Valle
Journal of Clinical Medicine, doi:10.3390/jcm10112378
Background: The immunomodulatory effects of vitamin D are known to be beneficial in viral infections; it is also known that its deficiency is associated with a prognosis more critical of Coronavirus Disease 2019. This study aimed to determine baseline vitamin D serum concentrations and the effects of its supplementation in asymptomatic or mildly symptomatic Coronavirus Disease 2019 outpatients. Methods: 42 outpatients were included, 22 of which received a supplement of 10,000 IU of vitamin D3 for 14 days; the remaining 20 outpatients were designated as a control group. Serum levels of transferrin, ferritin, vitamin D, and D-dimer were measured at baseline in both groups. After 14 days, serum levels of total vitamin D were determined in the supplemented group. Results: At baseline, only 19% of infected outpatients had vitamin D levels corresponding to sufficiency. All outpatients with vitamin D insufficiency had at least one symptom associated with the disease, while only 75% of patients with symptoms presented sufficiency. On the seventh and fourteenth day of follow-up, the supplemented group presented fewer symptoms with respect to those non-supplemented. A vitamin D3 dose of 10,000 IU/daily for 14 days was sufficient to raise vitamin D serum concentrations. Conclusions: Immunomodulatory effects of vitamin D appear to be linked to the development of symptoms in positive outpatients. Vitamin D supplementation could have significant benefits in the Western Mexican population.
References
Ajabshir, The Effects of Vitamin D on the Renin-Angiotensin System, Eff. Vitam. Renin. Angiotensin Syst,
doi:10.12860/jnp.2014.09Azrielant, Shoenfeld, Vitamin D and the Immune System, Israel Med. Assoc. J
Bedolla-Barajas, López-Hernández, García-Padilla, Morales-Romero, Velarde-Rivera et al., Prevalencia de insuficiencia y deficiencia de vitamina D en adultos mexicanos con asma alérgica, Rev. Alerg. México,
doi:10.29262/ram.v64i2.255Bolondi, Russo, Gamberini, Circelli, Meca et al., Iron Metabolism and Lymphocyte Characterisation during Covid-19 Infection in ICU Patients: An Observational Cohort Study, World J. Emerg. Surg,
doi:10.1186/s13017-020-00323-2Cheng, Li, Li, Liu, Yan et al., Ferritin in the Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-analysis, J. Clin. Lab. Anal,
doi:10.1002/jcla.23618Clark, Vivanco-Muñoz, Piña, Rivas-Ruiz, Huitrón et al., High Prevalence of Hypovitaminosis D in Mexicans Aged 14 Years and Older and Its Correlation with Parathyroid Hormone, Arch. Osteoporos,
doi:10.1007/s11657-015-0225-4Conti, Induction of Pro-Inflammatory Cytokines (IL-1 and IL-6) and Lung Inflammation by COVID-19: Anti-Inflammatory Strategies, J. Biol. Regul. Homeost. Agents,
doi:10.23812/CONTI-EDancer, Parekh, Lax, D'souza, Zheng et al., Vitamin D Deficiency Contributes Directly to the Acute Respiratory Distress Syndrome (ARDS), Thorax,
doi:10.1136/thoraxjnl-2014-206680De Lucena, Da Silva Santos, De Lima, De Albuquerque Borborema, De Azevêdo et al., Mechanism of Inflammatory Response in Associated Comorbidities in COVID, Diabetes Metab. Syndr. Clin. Res. Rev,
doi:10.1016/j.dsx.2020.05.025Franco, Silva, Barreto, Relationship of Body Mass Index and Waist-to-Hip Ratio with Fibrinolytic Activity Measured as d-Dimer, Obes. Res. Clin. Pract,
doi:10.1016/j.orcp.2010.12.003Fu, Bruce, Wu, Giedroc, The S2 Cu( I ) Site in CupA from Streptococcus Pneumoniae Is Required for Cellular Copper Resistance, Metallomics,
doi:10.1039/C5MT00221DGrant, Lahore, Mcdonnell, Baggerly, French et al., Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients,
doi:10.3390/nu12040988Greiller, Martineau, Modulation of the Immune Response to Respiratory Viruses by Vitamin D, Nutrients,
doi:10.3390/nu7064240Jain, Chaurasia, Sengar, Singh, Mahor et al., Analysis of Vitamin D Level among Asymptomatic and Critically Ill COVID-19 Patients and Its Correlation with Inflammatory Markers, Sci. Rep,
doi:10.1038/s41598-020-77093-zJolliffe, Greenberg, Hooper, Griffiths, Camargo et al., Vitamin D Supplementation to Prevent Asthma Exacerbations: A Systematic Review and Meta-Analysis of Individual Participant Data, Lancet Respir. Med,
doi:10.1016/S2213-2600(17)30306-5Kell, Pretorius, Serum Ferritin Is an Important Inflammatory Disease Marker, as It Is Mainly a Leakage Product from Damaged Cells, Metallomics,
doi:10.1039/C3MT00347GLee, Park, Kwon, Ham, Kim et al., Decreased Lung Function Is Associated with Elevated Ferritin but Not Iron or Transferrin Saturation in 42,927 Healthy Korean Men: A Cross-Sectional Study, PLoS ONE,
doi:10.1371/journal.pone.0231057Linkins, Takach Lapner, Review of D-Dimer Testing: Good, Bad, and Ugly, Int. J. Lab. Hematol,
doi:10.1111/ijlh.12665Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D Supplementation to Prevent Acute Respiratory Tract Infections: Systematic Review and Meta-Analysis of Individual Participant Data, BMJ,
doi:10.1136/bmj.i6583Martínez-Zavala, López-Sánchez, Vergara-Lopez, Chávez-Tapia, Uribe et al., Vitamin D Deficiency in Mexicans Have a High Prevalence: A Cross-Sectional Analysis of the Patients from the Centro Médico Nacional 20 de Noviembre, Arch. Osteoporos,
doi:10.1007/s11657-020-00765-wMccartney, O'shea, Faul, Healy, Byrne et al., Vitamin D and SARS-CoV-2 Infection-Evolution of Evidence Supporting Clinical Practice and Policy Development: A Position Statement from the Covit-D Consortium, Ir. J. Med. Sci,
doi:10.1007/s11845-020-02427-9Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results, JAMA Netw. Open,
doi:10.1001/jamanetworkopen.2020.19722Nowaczewska, Wici Ński, Osi Ński, Kaźmierczak, The Role of Vitamin D in Primary Headache-from Potential Mechanism to Treatment, Nutrients,
doi:10.3390/nu12010243O'brien, Sandler, Taylor, Weinberg, Serum Vitamin D and Risk of Breast Cancer within Five Years, Environ. Health Perspect,
doi:10.1289/EHP943Pinzon, Angela, None
Pradana, Vitamin D Deficiency among Patients with COVID-19: Case Series and Recent Literature Review, Trop. Med. Health,
doi:10.1186/s41182-020-00277-wRadujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger et al., Vitamin D Deficiency and Outcome of COVID-19 Patients, Nutrients,
doi:10.3390/nu12092757Rastogi, Bhansali, Khare, Suri, Yaddanapudi et al., Short Term, High-Dose Vitamin D Supplementation for COVID-19 Disease: A Randomised, Placebo-Controlled, Study (SHADE Study), Postgrad. Med. J,
doi:10.1136/postgradmedj-2020-139065Sanyaolu, Okorie, Marinkovic, Patidar, Younis et al., Comorbidity and Its Impact on Patients with COVID, SN Compr. Clin. Med,
doi:10.1007/s42399-020-00363-4Shahid, Kalayanamitra, Mcclafferty, Kepko, Ramgobin et al., COVID -19 and Older Adults: What We Know, J. Am. Geriatr. Soc,
doi:10.1111/jgs.16472Shi, Liu, Fu, Xu, Wu et al., Vitamin D/VDR Signaling Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Maintaining the Integrity of the Pulmonary Epithelial Barrier, Mol. Med. Rep,
doi:10.3892/mmr.2015.4685Shitrit, Peled, Shitrit, .-G.; Meidan, Bendayan et al., An Association between Oxygen Desaturation and D-Dimer in Patients with Obstructive Sleep Apnea Syndrome, Thromb. Haemost,
doi:10.1160/TH05-02-0103Smith, Prytherch, Meredith, Schmidt, Featherstone, The Ability of the National Early Warning Score (NEWS) to Discriminate Patients at Risk of Early Cardiac Arrest, Unanticipated Intensive Care Unit Admission, and Death, Resuscitation,
doi:10.1016/j.resuscitation.2012.12.016Taneri, Gómez-Ochoa, Llanaj, Raguindin, Rojas et al., Anemia and Iron Metabolism in COVID-19: A Systematic Review and Meta-Analysis, Eur. J. Epidemiol,
doi:10.1007/s10654-020-00678-5Terpos, Ntanasis-Stathopoulos, Elalamy, Kastritis, Sergentanis et al., Hematological Findings and Complications of COVID, Am. J. Hematol,
doi:10.1002/ajh.25829Turrubiates-Hernández, Sánchez-Zuno, González-Estevez, Hernández-Bello, Macedo-Ojeda et al., Potential Immunomodulatory Effects of Vitamin D in the Prevention of Severe Coronavirus Disease 2019: An Ally for Latin America (Review), Int. J. Mol. Med,
doi:10.3892/ijmm.2021.4865Xu, Yang, Chen, Luo, Zhang et al., Vitamin D Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Regulation of the Renin-Angiotensin System, Mol. Med. Rep,
doi:10.3892/mmr.2017.7546Ye, Tang, Liao, Shaw, Deng et al., Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study, J. Am. Coll. Nutr,
doi:10.1080/07315724.2020.1826005Yuan, Huang, Ye, Chen, Huang et al., Changes of Hematological and Immunological Parameters in COVID-19 Patients, Int. J. Hematol,
doi:10.1007/s12185-020-02930-wYılmaz, Şen, Is Vitamin D Deficiency a Risk Factor for COVID-19 in Children?, Pediatr. Pulmonol,
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'abstract': '<jats:p>Background: The immunomodulatory effects of vitamin D are known to be beneficial in '
'viral infections; it is also known that its deficiency is associated with a prognosis more '
'critical of Coronavirus Disease 2019. This study aimed to determine baseline vitamin D serum '
'concentrations and the effects of its supplementation in asymptomatic or mildly symptomatic '
'Coronavirus Disease 2019 outpatients. Methods: 42 outpatients were included, 22 of which '
'received a supplement of 10,000 IU of vitamin D3 for 14 days; the remaining 20 outpatients '
'were designated as a control group. Serum levels of transferrin, ferritin, vitamin D, and '
'D-dimer were measured at baseline in both groups. After 14 days, serum levels of total '
'vitamin D were determined in the supplemented group. Results: At baseline, only 19% of '
'infected outpatients had vitamin D levels corresponding to sufficiency. All outpatients with '
'vitamin D insufficiency had at least one symptom associated with the disease, while only 75% '
'of patients with symptoms presented sufficiency. On the seventh and fourteenth day of '
'follow-up, the supplemented group presented fewer symptoms with respect to those '
'non-supplemented. A vitamin D3 dose of 10,000 IU/daily for 14 days was sufficient to raise '
'vitamin D serum concentrations. Conclusions: Immunomodulatory effects of vitamin D appear to '
'be linked to the development of symptoms in positive outpatients. Vitamin D supplementation '
'could have significant benefits in the Western Mexican population.</jats:p>',
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