Ascorbic Acid Supplementation on D-dimer Levels in COVID-19 Patients

Authors

  • Reza Aditya Digambiro Faculty of Medicine, Universitas Trisakti, Jakarta, Indonesia
  • Dyah Ayu Woro Setyaningrum Faculty of Medicine, Universitas Trisakti, Jakarta, Indonesia
  • Florinda Ilona Faculty of Medicine, Universitas Trisakti, Jakarta, Indonesia
  • Julian Chendrasari Faculty of Medicine, Universitas Trisakti, Jakarta, Indonesia
  • Indah Widya Lestari Faculty of Medicine, Universitas Trisakti, Jakarta, Indonesia
  • Nanda Noor Muhammad Rumah Sakit Umum Daerah Tebet, Jakarta, Indonesia

DOI:

https://doi.org/10.36679/kedokteran.v10i1.103

Keywords:

ascorbic acid supplementation, d-dimer levels, covid-19

Abstract

Background: D-dimer is a potential biomarker for COVID-19 severity, correlated with the clinical outcomes and radiological findings. This research investigates the effect of ascorbic acid, an antioxidant and immunomodulator, on D-dimer levels in COVID-19 patients. Methods: The research design is prospective, randomized controlled, and conducted from January to March 2021 at Rumah Sakit Umum Daerah Tebet, Jakarta. Overall, 150 confirmed COVID-19 patients were randomized into two groups using a computer-generated block randomization technique. The intervention group received high-dose ascorbic acid (2 grams orally every 6 hours for seven days), while the control group received a placebo. Outcomes were assessed in changes in D-dimer levels, clinical severity, and radiological abnormalities. Statistical analyses included the Mann-Whitney, Wilcoxon signed-rank test, and logistic regression. Results: The patients treated with ascorbic acid showed a significant reduction in D-dimer levels compared to the placebo group. Additionally, these patients demonstrated notable improvements in clinical severity and radiological outcomes. The Wilcoxon signed-rank test demonstrated significant reductions in D-dimer levels within the ascorbic acid group (p < 0.001) and significant increases within the placebo group (p < 0.001). Conclusion: Ascorbic acid supplementation was associated with lowered D-dimer levels in COVID-19 patients, pointing to its potential therapeutic benefits in moderating disease severity. These results strongly support further research into ascorbic acid's benefits during COVID-19, especially for those at increased risk of severe disease progression.

References

Abdullah, F., Myers, J., Basu, D., Tintinger, G., Ueckermann, V., Mathebula, M., Ramlall, R., Spoor, S., de Villiers, T., Van der Walt, Z., Cloete, J., Soma-Pillay, P., Rheeder, P., Paruk, F., Engelbrecht, A., Lalloo, V., Myburg, M., Kistan, J., van Hougenhouck-Tulleken, W., … Jassat, W. (2022). Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in tshwane, south africa. International Journal of Infectious Diseases, 116, 38–42. https://doi.org/10.1016/j.ijid.2021.12.357

Abou-Ismail, M. Y., Diamond, A., Kapoor, S., Arafah, Y., & Nayak, L. (2020). The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management. In Thrombosis Research (Vol. 194, pp. 101–115). Elsevier Ltd. https://doi.org/10.1016/j.thromres.2020.06.029

Aljondi, R., & Alghamdi, S. (2020). Diagnostic value of imaging modalities for COVID-19: Scoping review. In Journal of Medical Internet Research (Vol. 22, Issue 8). JMIR Publications Inc. https://doi.org/10.2196/19673

Alsagaff, M. Y., Mulia, E. P. B., Maghfirah, I., Azmi, Y., Rachmi, D. A., Yutha, A., Andira, L. H., & Semedi, B. P. (2022). Low molecular weight heparin is associated with better outcomes than unfractionated heparin for thromboprophylaxis in hospitalized COVID-19 patients: a meta-analysis. European Heart Journal - Quality of Care and Clinical Outcomes, 8(8), 909–918. https://doi.org/10.1093/ehjqcco/qcac046

Behboudi, E., Nooreddin Faraji, S., Daryabor, G., Mohammad Ali Hashemi, S., Asadi, M., Edalat, F., Javad Raee, M., & Hatam, G. (2024). SARS-CoV-2 mechanisms of cell tropism in various organs considering host factors. In Heliyon (Vol. 10, Issue 4). Elsevier Ltd. https://doi.org/10.1016/j.heliyon.2024.e26577

Cabral-Pacheco, G. A., Garza-Veloz, I., Rosa, C. C. D. La, Ramirez-Acuña, J. M., Perez-Romero, B. A., Guerrero-Rodriguez, J. F., Martinez-Avila, N., & Martinez-Fierro, M. L. (2020). The roles of matrix metalloproteinases and their inhibitors in human diseases. International Journal of Molecular Sciences, 21(24), 1–53. https://doi.org/10.3390/ijms21249739

Cozzi, D., Cavigli, E., Moroni, C., Smorchkova, O., Zantonelli, G., Pradella, S., & Miele, V. (2021). Ground-glass opacity (GGO): a review of the differential diagnosis in the era of COVID-19. In Japanese Journal of Radiology (Vol. 39, Issue 8, pp. 721–732). Springer Japan. https://doi.org/10.1007/s11604-021-01120-w

Cucinotta, D., & Vanelli, M. (2020). WHO declares COVID-19 a pandemic. In Acta Biomedica (Vol. 91, Issue 1, pp. 157–160). Mattioli 1885. https://doi.org/10.23750/abm.v91i1.9397

Deutsch, E. (2001). The declaration of helsinki revised by the world medical organization, Edinburgh 2000. http://onlineethics.org/reseth/helsinki.html

Du, W. N., Zhang, Y., Yu, Y., & Zhang, R. M. (2021). D-dimer levels is associated with severe COVID-19 infections: A meta-analysis. International Journal of Clinical Practice, 75(8). https://doi.org/10.1111/ijcp.14031

Gęgotek, A., & Skrzydlewska, E. (2022). Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid. In Antioxidants (Vol. 11, Issue 10). MDPI. https://doi.org/10.3390/antiox11101993

Goswami, J., Macarthur, T. A., Sridharan, M., Pruthi, R. K., McBane, R. D., Witzig, T. E., & Park, M. S. (2021). A Review of Pathophysiology, Clinical Features, and Management Options of COVID-19 Associated Coagulopathy. In Shock (Vol. 55, Issue 6, pp. 700–716). Lippincott Williams and Wilkins. https://doi.org/10.1097/SHK.0000000000001680

Hemraj, S. K., Jacob, M. J., Kotian, V., K., S. D., G., G. R., & Veliath, L. B. (2022). Chest CT Findings and Their Temporal Evolution in COVID-19 Pneumonia. Cureus. https://doi.org/10.7759/cureus.26021

Herdiman, H., Basyar, M., & Khairsyaf, O. (2022). Association Between D-dimer Level with Clinical Severity and Radiological Imaging of Confirmed COVID-19 Patients at RSUP Dr. M. Djamil Padang. Jurnal Respirologi Indonesia, 42(4), 328–334. https://doi.org/10.36497/jri.v42i4.241

Khan, A. H., Tirth, V., Fawzy, M., Mahmoud, A. E. D., Khan, N. A., Ahmed, S., Ali, S. S., Akram, M., Hameed, L., Islam, S., Das, G., Roy, S., & Dehghani, M. H. (2021). COVID-19 transmission, vulnerability, persistence and nanotherapy: a review. In Environmental Chemistry Letters (Vol. 19, Issue 4, pp. 2773–2787). Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1007/s10311-021-01229-4

Lotfi, M., Hamblin, M. R., & Rezaei, N. (2020). COVID-19: Transmission, prevention, and potential therapeutic opportunities. In Clinica Chimica Acta (Vol. 508, pp. 254–266). Elsevier B.V. https://doi.org/10.1016/j.cca.2020.05.044

Mukherjee, S., & Pahan, K. (2021). Is COVID-19 Gender-sensitive? In Journal of Neuroimmune Pharmacology (Vol. 16, Issue 1, pp. 38–47). Springer. https://doi.org/10.1007/s11481-020-09974-z

Nasif, W. A., El-Moursy Ali, A. S., Hasan Mukhtar, M., Alhuzali, A. M. H., Yahya Alnashri, Y. A., Ahmed Gadah, Z. I., Edrees, E. A. A., Albarakati, H. A. M., & Muhji Aloufi, H. S. (2022). Elucidating the Correlation of D-dimer Levels with COVID-19 Severity: A Scoping Review. In Anemia (Vol. 2022). Hindawi Limited. https://doi.org/10.1155/2022/9104209

Neethu R.S.., Reddy, M. V. N. J., Batra, S., Srivastava, S. K., & Syal, K. (2022). Vitamin C and its therapeutic potential in the management of COVID19. In Clinical Nutrition ESPEN (Vol. 50, pp. 8–14). Elsevier Ltd. https://doi.org/10.1016/j.clnesp.2022.05.026

Niculae, C. M., Hristea, A., & Moroti, R. (2023). Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review. In Biomedicines (Vol. 11, Issue 3). MDPI. https://doi.org/10.3390/biomedicines11030929

Ozen, M., Yilmaz, A., Cakmak, V., Beyoglu, R., Oskay, A., Seyit, M., & Senol, H. (2021). D-dimer as a potential biomarker for disease severity in COVID-19. American Journal of Emergency Medicine, 40, 55–59. https://doi.org/10.1016/j.ajem.2020.12.023

Reda, S., Thiele Serra, E., Müller, J., Hamedani, N. S., Oldenburg, J., Pötzsch, B., & Rühl, H. (2022). Increased Prevalence of Elevated D-dimer Levels in Patients on Direct Oral Anticoagulants: Results of a Large Retrospective Study. Frontiers in Cardiovascular Medicine, 9. https://doi.org/10.3389/fcvm.2022.830010

Surendra, H., Praptiningsih, C. Y., Ersanti, A. M., Rahmat, M., Noviyanti, W., Harman, A. D., Mansu, A. N., Suleman, Y. Y., Sudrani, S., Rosalina, R., Mukhtar, I., Rosadi, D., Fauzi, L., Elyaza, R. F., Hawley, W. A., & Wibisono, H. (2023). Clinical characteristics and factors associated with COVID-19-related mortality and hospital admission during the first two epidemic waves in 5 rural provinces in Indonesia: A retrospective cohort study. PLoS ONE, 18(3 March). https://doi.org/10.1371/journal.pone.0283805

Tjahjadi, M., Caropeboka, S., Permana, C., Susanto, K., & Susanto, E. (2022). Long-Delayed Manifestation of COVID-19 Coagulopathy Presenting with Severe Cerebral Venous Thrombosis Causes Massive Brain Hemorrhage. Asian Journal of Neurosurgery, 17(02), 342–346. https://doi.org/10.1055/s-0042-1750388

Trimaille, A., Thachil, J., Marchandot, B., Curtiaud, A., Leonard-Lorant, I., Carmona, A., Matsushita, K., Sato, C., Sattler, L., Grunebaum, L., Hansmann, Y., Fafi-Kremer, S., Jesel, L., Ohana, M., & Morel, O. (2021). D-dimers level as a possible marker of extravascular fibrinolysis in covid-19 patients. Journal of Clinical Medicine, 10(1), 1–13. https://doi.org/10.3390/jcm10010039

Uddin, M. S., Millat, M. S., Baral, P. K., Ferdous, M., Uddin, M. G., Sarwar, M. S., & Islam, M. S. (2021). The protective role of vitamin C in the management of COVID-19: A Review. In Journal of the Egyptian Public Health Association (Vol. 96, Issue 1). Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1186/s42506-021-00095-w

Valdivia-Mazeyra, M. F., Salas, C., Nieves-Alonso, J. M., Martín-Fragueiro, L., Bárcena, C., Muñoz-Hernández, P., Villar-Zarra, K., Martín-López, J., Ramasco-Rueda, F., Fraga, J., & Jiménez-Heffernan, J. A. (2021). Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature. Virchows Archiv, 478(3), 487–496. https://doi.org/10.1007/s00428-020-02926-1

Vázquez, Y., González, L., Noguera, L., González, P. A., Riedel, C. A., Bertrand, P., & Bueno, S. M. (2019). Cytokines in the respiratory airway as biomarkers of severity and prognosis for respiratory syncytial virus infection: An update. In Frontiers in Immunology (Vol. 10, Issue JUN). Frontiers Media S.A. https://doi.org/10.3389/fimmu.2019.01154

Zaher, K., Basingab, F., Alrahimi, J., Basahel, K., & Aldahlawi, A. (2023). Gender Differences in Response to COVID-19 Infection and Vaccination. In Biomedicines (Vol. 11, Issue 6). MDPI. https://doi.org/10.3390/biomedicines11061677

Zhan, H., Chen, H., Liu, C., Cheng, L., Yan, S., Li, H., & Li, Y. (2021). Diagnostic Value of D-dimer in COVID-19: A Meta-Analysis and Meta-Regression. Clinical and Applied Thrombosis/Hemostasis, 27. https://doi.org/10.1177/10760296211010976

Zhang, G., Iwase, H., Li, Q., Yamamoto, T., Jagdale, A., Ezzelarab, M. B., Ayares, D., Cooper, D. K. C., Hara, H., & Wang, G. (2021). The Role of Interleukin-6 (IL-6) in the Systemic Inflammatory Response in Xenograft Recipients and in Pig Kidney Xenograft Failure. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.788949

Zhang, H., Penninger, J. M., Li, Y., Zhong, N., & Slutsky, A. S. (2020). Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Medicine, 46(4), 586–590. https://doi.org/10.1007/s00134-020-05985-9

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Published

2024-12-25

How to Cite

Digambiro, R. A., Setyaningrum, D. A. W., Ilona, F., Chendrasari, J., Lestari, I. W., & Muhammad, N. N. (2024). Ascorbic Acid Supplementation on D-dimer Levels in COVID-19 Patients. Jurnal Kedokteran: Media Informasi Ilmu Kedokteran Dan Kesehatan, 10(1), 37–46. https://doi.org/10.36679/kedokteran.v10i1.103