The Effects of 10,000 IU Vitamin D Supplementation on Improvement of Clinical Outcomes, Inflammatory and Coagulation Markers in Moderate COVID-19 Patients: A Randomized-Controlled Trial

Autores

  • Nurpudji Astuti Taslim Department of Clinical Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, 90245, Indonesia
  • Agussalim Bukhari Department of Nutritional Science, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Suryani As'ad Department of Nutritional Science, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Haerani Rasyid
  • Irawaty Djaharuddin Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Mardiana Madjid
  • Sisca Agustia Olii
  • Zahratul Fajri
  • A Yasmin Syauki

DOI:

https://doi.org/10.12873/432taslim

Palavras-chave:

COVID-19, Vitamin D, Clinical Outcome, Nutritional Status, Inflammatory markers, Coagulopathy

Resumo

Background & aims: Vitamin D supplementation as an immunomodulator has been identified as a potential strategy to prevent and treat Coronavirus disease 2019 (COVID-19). We aimed to analyze the effect of 10,000 IU vitamin D3 supplementation on 25(OH)D levels on primary clinical outcomes (conversion length), inflammatory markers (Total Lymphocyte Count (TLC), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR)) and coagulation marker (D-Dimer) in moderate COVID-19 patients at Wahidin Sudirohusodo Hospital, Makassar, Indonesia. Methods: We conducted a single-blind randomized-controlled trial on the confirmed moderate COVID-19 patients above 18 years old and low vitamin D status. Each of intervention and control groups were supplemented of 10,000 IU and 1000 IU cholecalciferol that taken daily for 2 weeks. Levels of 25(OH)D were analyzed for the primary endpoint (conversion length), then correlated to secondary endpoints (Length of Stay (LOS)), clinical manifestations improvement, and markers TLC, NLR, PLR, and D-Dimer serum, handgrip strength (HGS) as functional capacity measurement, after adjusted to age, sex, nutritional status based on body mass index (BMI) and Subjective Global Assessment (SGA) tool, comorbidities, and anti-coagulant administration. Results:  The Vitamin D3 supplementation of 10,000 IU and 1000 IU could significantly increase 25(OH)D levels compared to the control group of 1000 IU (4.61+5.43 vs. -0.29+2.72; P <0.0001) and it was correlated to primary clinical outcome, which is length of conversion (6.53+1.17 vs 10.47+2.56; P < 0.0001). The increase in HGS (6.61+3.01 vs. 4.04+4.44; P = 0.011), LOS (11.63+2.5 vs. 14.73+3.45; P = 0.001), and improvement in clinical manifestations were found to be significant in both groups. Conclusion: Supplementation of vitamin D3 10,000 IU in moderate COVID-19 patients had a significant effect on 25(OH)D level, length of conversion, LOS, functional capacity, and PLR levels, but it has negative correlation in TLC, NLR, and D-Dimer levels.

Referências

(PDPI), Indonesian Lung Doctors Association. 2022. Guidelines for the Management of COVID-19. 4th ed. edited by E. Burhan. Jakarta.

Altaş, Elif Umay, and Aliye Tosun. 2018. “Assessment of Vitamin D and Inflammatory Response Relationship Using Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio and Mean Platelet Volume.” Turk Osteoporoz Dergisi 24(1):11–14. doi: 10.4274/tod.07108.

Bayramoğlu, Elvan, Gülşen Akkoç, Ayşe Ağbaş, zlem Akgün, Kamer Yurdakul, Hatice Nilgün Selçuk Duru, and Murat Elevli. 2021. “The Association between Vitamin D Levels and the Clinical Severity and Inflammation Markers in Pediatric COVID-19 Patients: Single-Center Experience from a Pandemic Hospital.” European Journal of Pediatrics 180(8):2699–2705. doi:10.1007/s00431-021-04030-1.

Bennasrallah, Cyrine, Imen Zemni, Wafa Dhouib, Haythem Sriha, Nourhene Mezhoud, Samar Bouslama, Wael Taboubi, Meriem Oumaima Beji, Meriem Kacem, Hela Abroug, Manel Ben Fredj, Chawki Loussaief, and Asma Sriha Belguith. 2021. “Factors Associated with a Prolonged Negative Conversion of Viral RNA in Patients with COVID-19.” International Journal of Infectious Diseases 105:463–69. doi: 10.1016/j.ijid.2021.02.089.

Berhandus, Catrien, Jeffrey A. Ongkowijaya, and Karel Pandelaki. 2021. “Relationship of Vitamin D Levels and C-Reactive Protein Levels with Clinical Coronavirus Disease 2019 Patients.” E-CliniC 9(2):370. doi:10.35790/ecl.v9i2.33043.

Fiorindi, C., F. Campani, L. Rasero, C. Campani, L. Livi, L. Giovannoni, C. Amato, F. Giudici, A. Bartoloni, F. Fattirolli, F. Lavorini, I. Olivotto, and A. Nannoni. 2021. “Prevalence of Nutritional Risk and Malnutrition during and after Hospitalization for COVID-19 Infection: Preliminary Results of a Single-Centre Experience.” Clinical Nutrition ESPEN 45:351–55. doi:10.1016/j.clnesp.2021.07.020.

Guan, Wei-jie, Zheng-yi Ni, Yu Hu, Wen-hua Liang, Chun-quan Ou, Jian-xing He, Lei Liu, Hong Shan, Chun-liang Lei, David SC Hui, Bin Du, Lan-juan Li, Guang Zeng, Kwok-Yung Yuen, Ru-chong Chen, Chun-li Tang, Tao Wang, Ping-yan Chen, Jie Xiang, Shi-yue Li, Jin-lin Wang, Zi-jing Liang, Yi-xiang Peng , Li Wei, Yong Liu, Ya-hua Hu, Peng Peng, Jian-ming Wang, Ji-yang Liu, Zhong Chen, Gang Li, Zhi-jian Zheng, Shao-qin Qiu, Jie Luo, Chang-jiang Ye, Shao -yong Zhu, and Nan-shan Zhong. 2020. “Clinical Characteristics of Coronavirus Disease 2019 in China.” New England Journal of Medicine 382(18):1708–20. doi:10.1056/nejmoa2002032.

Handajani, Yvonne Suzy, Yuda Turana, and Nelly Tina Widjaja. 2016. "Effects of Decreased Hand Grip Strength on Cognitive Function and Balance in the Elderly." 34(1):13–18.

Huang, Ian, and Raymond Pranata. 2020. “Lymphopenia in Severe Coronavirus Disease-2019 (COVID-19): Systematic Review and Meta-Analysis.” Journal of Intensive Care 8(1):1–10. doi:10.1186/s40560-020-00453-4.

Ikewaki, Nobunao, Kosagi Sharaf Rao, Armando Durant Archibold, Masaru Iwasaki, Rajappa Senthilkumar, Senthilkumar Preethy, Shojiro Katoh, and Samuel JK Abraham. 2020. “Coagulopathy Associated with COVID-19 – Perspectives & Preventive Strategies Using a Biological Response Modifier Glucan.” Thrombosis Journal 18(1):1–8. doi:10.1186/s12959-020-00239-6.

King, Eshani. 2020. “The Role of Vitamin D Deficiency in COVID-19 Related Deaths in BAME, Obese and Other High-Risk Categories.” 25:1–19. doi:10.31232/osf.io/73whx.

Kollias, Anastasios, Konstantinos G. Kyriakoulis, Evangelos Dimakakos, Garyphallia Poulakou, George S. Stergiou, and Konstantinos Syrigos. 2020. “Thromboembolic Risk and Anticoagulant Therapy in COVID-19 Patients: Emerging Evidence and Call for Action.” British Journal of Haematology 189(5):846–47. doi:10.1111/bjh.16727.

Soraya Cherifi, Mario Manto, Justin Michel, Thomas Radulesco, Gabriele Molteni, Manuel Tucciarone, Giuditta Mannelli, and Giovanna Cantarella. 2020. “Clinical and Epidemiological Characteristics of 1420 European Patients with Mild‐to‐moderate Coronavirus Disease 2019.” Journal of Internal Medicine 288(3):335–44. doi: 10.1111/joim.13089.

Li, Gang, Chen-liang Zhou, Yuan-ming Ba, Ye-ming Wang, Bin Song, Xiao-bin Cheng, Qiu-fen Dong, Liu-lin Wang, and Sha-sha You. 2020. “Nutritional Risk and Therapy for Severe and Critical COVID-19 Patients: A Multicenter Retrospective Observational Study.” Clinical Nutrition (xxxx). doi: 10.1016/j.clnu.2020.09.040.

Liu, Jiao, Sheng Zhang, Zhixiong Wu, You Shang, Xuan Dong, Guang Li, Lidi Zhang, Yizhu Chen, Xiaofei Ye, Hangxiang Du, Yongan Liu, Tao Wang, SiSi Huang, Limin Chen, Zhenliang Wen, Jieming Qu, and Dechang Chen. 2020. “Clinical Outcomes of COVID-19 in Wuhan, China: A Large Cohort Study.” Annals of Intensive Care 10(1):99. doi:10.1186/s13613-020-00706-3.

Ludwig, Marion, Josephine Jacob, Frederike Basedow, Frank Andersohn, and Jochen Walker. 2021. “Clinical Outcomes and Characteristics of Patients Hospitalized for Influenza or COVID-19 in Germany.” International Journal of Infectious Diseases 103:316–22. doi: 10.1016/j.ijid.2020.11.204.

Mahenthiran, Ajay K., Ashorne K. Mahenthiran, and Jo Mahenthiran. 2020. “Cardiovascular System and COVID-19: Manifestations and Therapeutics.” Reviews in Cardiovascular Medicine 21(3):399–409. doi: 10.31083/j.rcm. 2020.03.124.

Manson, Jo Ann E., and Shari S. Bassuk. 2020. “Commentary. Eliminating Vitamin D Deficiency during the COVID-19 Pandemic: A Call to Action.” Metabolism: Clinical and Experimental 112:154322. doi: 10.1016/j.metabol.2020.154322.

Meltzer, David O., Thomas J. Best, Hui Zhang, Tamara Vokes, Vineet Arora, and Julian Solway. 2020. “Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results.” JAMA Network Open 3(9):e2019722. doi: 10.1001/jamanetworkopen.2020.19722.

Merzon, Eugene, Dmitry Tworowski, Alessandro Gorohovski, Shlomo Vinker, Avivit Golan Cohen, Ilan Green, and Milana Frenkel-Morgenstern. 2020. “Low Plasma 25(OH) Vitamin D Level Is Associated with Increased Risk of COVID-19 Infection: An Israeli Population-Based Study.” FEBS Journal 287(17):3693–3702. doi: 10.1111/febs.15495.

Kazemijahromi's partner, Hamid Reza. 2021. “The Association of Vitamin D Deficiency with COVID-19 Severity and Mortality.” Endocrine Abstract.

Moriconi, Diego, Stefano Masi, Eleni Rebelos, Agostino Virdis, Maria Laura Manca, Salvatore De Marco, Stefano Taddei, and Monica Nannipieri. 2020. “Obesity Prolongs the Hospital Stay in Patients Affected by COVID-19, and May Impact on SARS-COV-2 Shedding.” Obesity Research & Clinical Practice 14(3):205–9. doi: 10.1016/j.orcp.2020.05.009.

Mousa, Aya, Marie Misso, Helena Teede, Robert Scragg, and Barbora De Courten. 2016. “Effect of Vitamin D Supplementation on Inflammation: Protocol for a Systematic Review.” BMJ Open 6(4):1–5. doi:10.1136/bmjopen-2015-010804.

Murai, Igor H., Alan L. Fernandes, Lucas P. Sales, 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, Bruna Z. Reis, Leila Antonangelo, Valeria F. Caparbo, Bruno Gualano, and Rosa MR Pereira. 2021. “Effect of a Single High Dose of Vitamin D3on Hospital Length of Stay in Patients with Moderate to Severe COVID-19: A Randomized Clinical Trial.” JAMA - Journal of the American Medical Association 325(11):1053–60. doi: 10.1001/jama.2020.26848.

Musselwhite, Laura W., Bruno B. Andrade, Susan S. Ellenberg, Ann Tierney, Pablo F. Belaunzaran-Zamudio, Adam Rupert, Michael M. Lederman, Ian Sanne, Juan G. Sierra Madero, and Irini Sereti. 2016. “Vitamin D, D-Dimer, Interferon , and SCD14 Levels Are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study.” EBioMedicine 4:115–23. doi: 10.1016/j.ebiom.2016.01.016.

Nicolau, Joana, Luisa Ayala, Pilar Sanchís, Josefina Olivares, Keyla Dotres, Ana-gloria Soler, Irene Rodríguez, Luis-Alberto Gómez, and Lluís Masmiquel. 2021. “Influence of Nutritional Status on Clinical Outcomes among Hospitalized Patients with COVID-19.” Clinical Nutrition ESPEN 43(January):223–29. doi:10.1016/j.clnesp.2021.04.013.

Orchard, Laurence, Matthew Baldry, Myra Nasim-Mohi, Chantelle Monck, Kordo Saeed, Michael PW Grocott, and Dushianthan Ahilanandan. 2021. “Vitamin-D Levels and Intensive Care Unit Outcomes of a Cohort of Critically Ill COVID-19 Patients.” Clinical Chemistry and Laboratory Medicine 59(6):1155–63. doi: 10.1515/cclm-2020-1567.

Panigrahy, Dipak, Molly M. Gilligan, Sui Huang, Allison Gartung, Irene Cortés-Puch, Patricia J. Sime, Richard P. Phipps, Charles N. Serhan, and Bruce D. Hammock. 2020. “Inflammation Resolution: A Dual-Pronged Approach to Averting Cytokine Storms in COVID-19?” Cancer and Metastasis Reviews 39(2):337–40. doi:10.1007/s10555-020-09889-4.

Rastogi, Ashu, Anil Bhansali, Niranjan Khare, Vikas Suri, Narayana Yaddanapudi, Naresh Sachdeva, GD Puri, and Pankaj Malhotra. 2020. “Short Term, High-Dose Vitamin D Supplementation for COVID-19 Disease: A Randomised, Placebo-Controlled, Study (SHADE Study).” Postgraduate Medical Journal 1-4. doi: 10.1136/postgradmedj-2020-139065.

Rees, Eleanor M., Emily S. Nightingale, Yalda Jafari, Naomi R. Waterlow, Samuel Clifford, Carl AB Pearson, Cmmid Working Group, Thibaut Jombart, Simon R. Procter, and Gwenan M. Knight. 2020. “COVID-19 Length of Hospital Stay: A Systematic Review and Data Synthesis.” BMC Medicine 18(1):270. doi:10.1186/s12916-020-01726-3.

Roth, Gregory A., Sophia Emmons-Bell, Heather M. Alger, Steven M. Bradley, Sandeep R. Das, James A. de Lemos, Emmanuela Gakidou, Mitchell SV Elkind, Simon Hay, Jennifer L. Hall, Catherine O. Johnson, David A. Morrow, Fatima Rodriguez, Christine Rutan, Saate Shakil, Reed Sorensen, Laura Stevens, Tracy Y. Wang, Jason Walchok, Joseph Williams, and Christopher Murray. 2021. “Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic.” JAMA Network Open 4(5):e218828. doi:10.1001/jamanetworkopen.2021.8828.

Sabico, Shaun, Mushira A. Enani, Eman Sheshah, Naji J. Aljohani, Dara A. Aldisi, Naif H. Alotaibi, Naemah Alshingetti, Suliman Y. Alomar, Abdullah M. Alnaami, Osama E. Amer, Syed D. Hussain, and Nasser M. Al-Daghri. 2021. “Effects of a 2-Week 5000 Iu versus 1000 Iu Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.” Nutrients 13(7). doi: 10.3390/nu13072170.

Sari, Shinta Dewi Permata, Wening Tri Mawanti, Dewi Martalena, Erlin Listiyaningsih, Rizkyana Avissa, Rini Latifah, and Wawang S. Sukarya. 2021. “Pro-Inflammatory Cytokine (IL-6) and Total Count Lymphocyte Profiles in COVID-19 Patients with Different Severity Levels.” Journal of Thee Medical Sciences 53(3):218–25. doi: 10.19106/jmedsci005303202101.

Sepandi, Mojtaba, Maryam Taghdir, Yousef Alimohamadi, Sima Afrashteh, and Hadiseh Hosamirudsari. 2020. “Factors Associated with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis.” Iranian Journal of Public Health 49(7):1211–21. doi:10.18502/ijph.v49i7.3574.

Shareef, Rawaa Hadi, Zinah Dhiaa Zwain, and Wadhah Abdulhussian Mahbuba. 2021. “Superiority of Lymphocyte Ratio over Total Leukocyte Count in Detecting the Severity of COVID-19 Pneumonia.” Heliyon 7(11):e08412. doi: 10.1016/j.heliyon.2021.e08412.

Song, Xinyu, Dawei Chen, Ma Yuan, Haiyong Wang, and Zhehai Wang. 2018. “Total Lymphocyte Count, Neutrophil–Lymphocyte Ratio, and Platelet–Lymphocyte Ratio as Prognostic Factors in Advanced Non–Small Cell Lung Cancer with Chemoradiotherapy.” Cancer Management and Research 10:6677–83. doi:10.2147/CMAR.S188578.

Spagnolo, Primavera A., JoAnn E. Manson, and Hadine Joffe. 2020. “Sex and Gender Differences in Health: What the COVID-19 Pandemic Can Teach Us.” Annals of Internal Medicine 173(5):385–86. doi: 10.7326/M20-1941.

Susilo, Adityo, C. Martin Rumende, Ceva W. Pitoyo, Widayat Djoko Santoso, Mira Yulianti, Robert Sinto, Gurmeet Singh, Leonard Nainggolan, Erni J. Nelwan, Lie Khie, Alvina Widhani, Edwin Wijaya, Bramantya Wicaksana, Maradewi Maksum, Firda Annisa, OM Jasirwan, Evy Yunihastuti, Handling Team, New Infections, Re-emerging Disease Pinere, and Cipto Hospital. 2020. “Coronavirus Disease 2019: Review of Current Literature Coronavirus Disease 2019: Review of Current Literatures.” Indonesian Journal of Internal Medicine 7(1):45–67.

Wacker, Matthias, and Michael F. Holick. 2013. “A Global Perspective for Health.” Dermato-Endocrinology 5(March):51–108.

Wang, Jing, Xuena Wang, Yeqing Gu, Mingyue Liu, Vu Thi Quynh Chi, Qing Zhang, Li Liu, Ge Meng, Zhanxin Yao, Hongmei Wu, Xue Bao, Shunming Zhang, Yanyan Wang, Zuolin Lu, Liu Wang, Lixiao Zheng , Xiaona Wang, Chunling Tian, Jingzhu Fu, Shaomei Sun, Ming Zhou, Qiyu Jia, Kun Song, Jian Huang, Junsheng Huo, Bing Zhang, Gangqiang Ding, and Kaijun Niu. 2019. “Vitamin D Is Related to Handgrip Strength in Adult Men Aged 50 Years and over: A Population Study from the TCLSIH Cohort Study.” Clinical Endocrinology 90(5):753–65. doi: 10.1111/cen.13952.

Wu, Yi Chi, Ching Sung Chen, and Yu Jiun Chan. 2020. “The Outbreak of COVID-19: An Overview.” Journal of the Chinese Medical Association 83(3):217–20. doi:10.1097/JCMA.0000000000000270.

Yang, Ai Ping, Jian ping Liu, Wen qiang Tao, and Hui ming Li. 2020. “The Diagnostic and Predictive Role of NLR, d-NLR and PLR in COVID-19 Patients.” International Immunopharmacology 84(April):106504. doi: 10.1016/j.intimp.2020.106504.

Yue, Xiangfeng, Min Li, Yu Wang, Jing Zhang, Xinyi Wang, Linwei Kan, Xiaojian Zhang, and Shuzhang Du. 2020. “Nutritional Support and Clinical Outcome of Severe and Critical Patients With COVID-19 Pneumonia.” Frontiers in Nutrition 7(November):1–7. doi: 10.3389/fnut.2020.581679.

Zhao, Qianwen, Meng Meng, Rahul Kumar, Yinlian Wu, Jiaofeng Huang, Yunlei Deng, Zhiyuan Weng, and Li Yang. 2020. “Lymphopenia Is Associated with Severe Coronavirus Disease 2019 (COVID-19) Infections: A Systemic Review and Meta-Analysis.” International Journal of Infectious Diseases 96(2020):131–35. doi: 10.1016/j.ijid.2020.04.086.

Zhou, Fei, Ting Yu, Ronghui Du, Guohui Fan, Ying Liu, Zhibo Liu, Jie Xiang, Yeming Wang, Bin Song, Xiaoying Gu, Lulu Guan, Yuan Wei, Hui Li, Xudong Wu, Jiuyang Xu, Shengjin Tu, Yi Zhang, Hua Chen, and Bin Cao. 2020. “Clinical Course and Risk Factors for Mortality of Adult Inpatients with COVID-19 in Wuhan, China: A Retrospective Cohort Study.” The Lancet 395(10229):1054–62. doi:10.1016/S0140-6736(20)30566-3.

Zhou, Peng, Xing Lou Yang, Xian Guang Wang, Ben Hu, Lei Zhang, Wei Zhang, Hao Rui Si, Yan Zhu, Bei Li, Chao Lin Huang, Hui Dong Chen, Jing Chen, Yun Luo, Hua Guo, Ren Di Jiang, Mei Qin Liu, Ying Chen, Xu Rui Shen, Xi Wang, Xiao Shuang Zheng, Kai Zhao, Quan Jiao Chen, Fei Deng, Lin Lin Liu, Bing Yan, Fa Xian Zhan, Yan Yi Wang, Geng Fu Xiao, and Zheng Li Shi. 2020. “A Pneumonia Outbreak Associated with a New Coronavirus of Probable Bat Origin.” Nature 579(7798):270–73. doi:10.1038/s41586-020-2012-7.

Publicado

2023-05-01

Como Citar

Taslim, N. A., Bukhari, A., As’ad, S., Rasyid, H., Djaharuddin, I., Madjid, M., … Syauki, A. Y. (2023). The Effects of 10,000 IU Vitamin D Supplementation on Improvement of Clinical Outcomes, Inflammatory and Coagulation Markers in Moderate COVID-19 Patients: A Randomized-Controlled Trial. Nutrición Clínica Y Dietética Hospitalaria, 43(2). https://doi.org/10.12873/432taslim

Edição

Seção

Artículos originales

Categorias

Artigos mais lidos pelo mesmo(s) autor(es)

1 2 > >>