Skip to main navigation menu Skip to main content Skip to site footer

Clinical Research

Vol 9 No 2 (2024): December

Higher Serum Level of MMP-3 and Homocysteine in Patients Admitted With COVID-19
Tingkat Serum MMP-3 dan Homosistein yang Lebih Tinggi pada Pasien yang Dirawat dengan COVID-19



(*) Corresponding Author
DOI
https://doi.org/10.21070/acopen.9.2024.10301
Published
October 15, 2024

Abstract

Background: SARS-CoV-2 predominantly affects the lungs, leading to severe acute respiratory syndrome (ARDS). The lack of specific biomarkers underscores the urgent need for novel indicators for early diagnosis and severity assessment of COVID-19. Specific Background: Matrix metalloproteinase-3 (MMP-3) is implicated in various inflammatory diseases, particularly viral infections, while homocysteine (Hcy) plays a crucial role in maintaining cell homeostasis and regulating inflammatory responses. Knowledge Gap: Despite their relevance in inflammation, the potential of MMP-3 and Hcy as biomarkers for COVID-19 remains underexplored. Aims: This study aimed to evaluate the serum levels of MMP-3 and Hcy in COVID-19 patients and assess their utility in diagnosis and severity prediction. Results: A study analyzing 90 serum samples from 60 ICU patients and 30 healthy controls found elevated CRP levels, higher Hcy and MMP-3 levels in the moderate group, but lower in the ICU group, with a significant correlation between MMP-3 activity and Hcy levels. Novelty: This research highlights the potential role of MMP-3 and Hcy as valuable biomarkers for COVID-19 diagnosis. Implications: While MMP-3 and homocysteine may aid in the diagnostic process, they could not be reliably used to predict severity outcomes in COVID-19 patients. Further studies are warranted to clarify the clinical implications of these biomarkers in the context of COVID-19.

Highlights:

 

  1. MMP-3 and homocysteine identified as potential COVID-19 biomarkers.
  2. No correlation found between biomarkers and disease severity.
  3. Further research needed for clinical utility assessment.

 

Keywords: COVID-19, MMP-3, homocysteine, biomarkers, diagnosis

References

  1. . S. S. Batah and A. T. Fabro, “Pulmonary Pathology of ARDS in COVID-19: A Pathological Review for Clinicians,” Respiratory Medicine, vol. 176, p. 106239, 2021.
  2. . World Health Organization, “Responding to Community Spread of COVID-19: Interim Guidance, 7 March 2020,” 2020.
  3. . C. Huang et al., “Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China,” The Lancet, vol. 395, no. 10223, pp. 497–506, 2020.
  4. . M. Sharif-zak et al., “CCR2 and DPP9 Expression in the Peripheral Blood of COVID-19 Patients: Influences of the Disease Severity and Gender,” Immunobiology, vol. 227, no. 2, p. 152184, 2022.
  5. . E. A. Wang, J. Zenilman, and L. Brinkley-Rubinstein, “Ethical Considerations for COVID-19 Vaccine Trials in Correctional Facilities,” JAMA, vol. 324, no. 11, pp. 1031–1032, 2020.
  6. . N. Chams et al., “COVID-19: A Multidisciplinary Review,” Frontiers in Public Health, vol. 8, p. 383, 2020.
  7. . F. Khatami et al., “A Meta-Analysis of Accuracy and Sensitivity of Chest CT and RT-PCR in COVID-19 Diagnosis,” Scientific Reports, vol. 10, no. 1, pp. 1–12, 2020.
  8. . Z. L. Zhang, Y. L. Hou, D. T. Li, and F. Z. Li, “Laboratory Findings of COVID-19: A Systematic Review and Meta-Analysis,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 80, no. 6, pp. 441–447, 2020.
  9. . S. Shi et al., “Matrix Metalloproteinase 3 as a Valuable Marker for Patients with COVID-19,” Journal of Medical Virology, vol. 93, no. 1, pp. 528–532, 2021.
  10. . A. Lerner et al., “MMP3 Is a Reliable Marker for Disease Activity, Radiological Monitoring, Disease Outcome Predictability, and Therapeutic Response in Rheumatoid Arthritis,” Best Practice & Research Clinical Rheumatology, vol. 32, no. 4, pp. 550–562, 2018.
  11. . L. Nissinen and V.-M. Kähäri, “Matrix Metalloproteinases in Inflammation,” Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1840, no. 8, pp. 2571–2580, 2014.
  12. . A. Davey, D. McAuley, and C. O'Kane, “Matrix Metalloproteinases in Acute Lung Injury: Mediators of Injury and Drivers of Repair,” European Respiratory Journal, vol. 38, no. 4, pp. 959–970, 2011.
  13. . R. Kadry, A. S. Newsome, and P. R. Somanath, “Pharmacological Inhibition of MMP3 as a Potential Therapeutic Option for COVID-19 Associated Acute Respiratory Distress Syndrome,” Infectious Disorders Drug Targets, vol. 21, no. 6, p. e170721187996, 2021.
  14. . A. Keskin et al., “Homocysteine as a Marker for Predicting Disease Severity in Patients with COVID-19,” Biomarkers in Medicine, vol. 16, no. 7, pp. 559–568, 2022.
  15. . J. D. Finkelstein and J. J. Martin, “Homocysteine,” The International Journal of Biochemistry & Cell Biology, vol. 32, no. 4, pp. 385–389, 2000.
  16. . R. Yoshitomi et al., “Plasma Homocysteine Concentration Is Associated with the Expression Level of Folate Receptor 3,” Scientific Reports, vol. 10, no. 1, pp. 1–8, 2020.
  17. . L. Koklesova et al., “Homocysteine Metabolism as the Target for Predictive Medical Approach, Disease Prevention, Prognosis, and Treatments Tailored to the Person,” EPMA Journal, vol. 12, no. 4, pp. 477–505, 2021.
  18. . F. Abike et al., “Human Papilloma Virus Persistence and Neopterin, Folate and Homocysteine Levels in Cervical Dysplasias,” Archives of Gynecology and Obstetrics, vol. 284, no. 1, pp. 209–214, 2011.
  19. . X. Roblin, J. Pofelski, and J.-P. Zarski, “Steatosis, Chronic Hepatitis Virus C Infection and Homocysteine,” Gastroenterologie Clinique et Biologique, vol. 31, no. 4, pp. 415–420, 2007.
  20. . Z. Yang et al., “Predictors for Imaging Progression on Chest CT from Coronavirus Disease 2019 (COVID-19) Patients,” Aging (Albany NY), vol. 12, no. 7, pp. 6037–6050, 2020.
  21. . A. Keskin, G. U. Ustun, R. Aci, and U. Duran, “Homocysteine as a Marker for Predicting Disease Severity in Patients with COVID-19,” Biomarkers in Medicine, vol. 16, no. 7, pp. 559–568, 2022.
  22. . Z. Fan et al., “Clinical Features of COVID-19-Related Liver Functional Abnormality,” Clinical Gastroenterology and Hepatology, vol. 18, no. 7, pp. 1561–1566, 2020.
  23. . K. C. Nerusu et al., “Matrix Metalloproteinase-3 (Stromelysin-1) in Acute Inflammatory Tissue Injury,” Experimental and Molecular Pathology, vol. 83, no. 2, pp. 169–176, 2007.
  24. . A. G. Vassiliou et al., “Endothelial Damage in Acute Respiratory Distress Syndrome,” International Journal of Molecular Sciences, vol. 21, no. 22, p. 8793, 2020.
  25. . R. L. Warner et al., “Matrix Metalloproteinases in Acute Inflammation: Induction of MMP-3 and MMP-9 in Fibroblasts and Epithelial Cells Following Exposure to Pro-Inflammatory Mediators In Vitro,” Experimental and Molecular Pathology, vol. 76, no. 3, pp. 189–195, 2004.
  26. . B. Hu, S. Huang, and L. Yin, “The Cytokine Storm and COVID-19,” Journal of Medical Virology, vol. 93, no. 1, pp. 250–256, 2021.
  27. . M. Gelzo et al., “Matrix Metalloproteinases (MMP) 3 and 9 as Biomarkers of Severity in COVID-19 Patients,” Scientific Reports, vol. 12, no. 1, p. 1212, 2022.
  28. . G. Ponti, C. Ruini, and A. Tomasi, “Homocysteine as a Potential Predictor of Cardiovascular Risk in Patients with COVID-19,” Medical Hypotheses, vol. 143, p. 109859, 2020.
  29. . I. Cheruiyot et al., “Arterial Thrombosis in Coronavirus Disease 2019 Patients: A Rapid Systematic Review,” Annals of Vascular Surgery, vol. 70, pp. 273–281, 2021.
  30. . J. E. Gomez-Mesa et al., “Thrombosis and Coagulopathy in COVID-19,” Current Problems in Cardiology, vol. 46, no. 3, p. 100742, 2021.
  31. . M. Bansal, “Cardiovascular Disease and COVID-19,” Diabetes & Metabolic Syndrome: Clinical Research & Reviews, vol. 14, no. 3, pp. 247–250, 2020.
  32. . F. Skovby, M. Gaustadnes, and S. H. Mudd, “A Revisit to the Natural History of Homocystinuria Due to Cystathionine β-Synthase Deficiency,” Molecular Genetics and Metabolism, vol. 99, no. 1, pp. 1–3, 2010.
  33. . H. Refsum et al., “The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease,” The Journal of Nutrition, vol. 134, no. 5, pp. 1121S–1128S, 2004.
  34. . F. J. van der Meer, T. Koster, J. Vandenbroucke, E. Briet, and F. R. Rosendaal, “The Leiden Thrombophilia Study (LETS),” Thrombosis and Haemostasis, vol. 78, no. 07, pp. 631–635, 1997.
  35. . G. Ponti, L. Roli, G. Oliva, M. Manfredini, T. Trenti, S. Kaleci, et al., “Homocysteine (Hcy) Assessment to Predict Outcomes of Hospitalized Covid-19 Patients: A Multicenter Study on 313 Covid-19 Patients,” Clinical Chemistry and Laboratory Medicine (CCLM), vol. 59, no. 9, pp. e354–e357, 2021.
  36. . A. Berbert, “Further Comment on Articles Pertaining to ‘Homocysteine as a Potential Predictor of Cardiovascular Risk in Patients with COVID-19’,” Medical Hypotheses, vol. 155, p. 110676, 2021.
  37. . O. Ć. Ibrahimagić, D. Smajlović, Z. Dostović, M. Vidović, E. Tupković, and S. Kunić, “Comment on an Article: ‘Homocysteine as a Potential Predictor of Cardiovascular Risk in Patients with COVID-19’,” Medical Hypotheses, vol. 143, p. 110107, 2020.
  38. . K. Tsarouhas, C. Tsitsimpikou, S. Apostolakis, A. Haliassos, M. Tzardi, M. Panagiotou, et al., “Homocysteine and Metalloprotease-3 and -9 in Patients with Ascending Aorta Aneurysms,” Thrombosis Research, vol. 128, no. 5, pp. e95–e99, 2011.
  39. . Y. Y. Luan, C. H. Yin, and Y. M. Yao, “Update Advances on C-Reactive Protein in COVID-19 and Other Viral Infections,” Frontiers in Immunology, vol. 12, p. 3153, 2021.
  40. . M. Kermali, R. K. Khalsa, K. Pillai, Z. Ismail, and A. Harky, “The Role of Biomarkers in Diagnosis of COVID-19—A Systematic Review,” Life Sciences, vol. 254, p. 117788, 2020.
  41. . W. Chen, K. I. Zheng, S. Liu, Z. Yan, C. Xu, and Z. Qiao, “Plasma CRP Level Is Positively Associated with the Severity of COVID-19,” Annals of Clinical Microbiology and Antimicrobials, vol. 19, no. 1, pp. 1–7, 2020.
  42. . B. R. Sahu, R. K. Kampa, A. Padhi, and A. K. Panda, “C-Reactive Protein: A Promising Biomarker for Poor Prognosis in COVID-19 Infection,” Clinica Chimica Acta, vol. 509, pp. 91–94, 2020.
  43. . Q. Li, X. Ding, G. Xia, H.-G. Chen, F. Chen, Z. Geng, et al., “Eosinopenia and Elevated C-Reactive Protein Facilitate Triage of COVID-19 Patients in Fever Clinic: A Retrospective Case-Control Study,” EClinicalMedicine, vol. 23, p. 100375, 2020.
  44. . M. Gelzo, S. Cacciapuoti, B. Pinchera, A. De Rosa, G. Cernera, F. Scialò, et al., “Matrix Metalloproteinases (MMP) 3 and 9 as Biomarkers of Severity in COVID-19 Patients,” Scientific Reports, vol. 12, no. 1, pp. 1–7, 2022.
  45. . E. Vespa, N. Pugliese, D. Piovani, A. Capogreco, S. Danese, and A. Aghemo, “Liver Tests Abnormalities in COVID-19: Trick or Treat?” Journal of Hepatology, vol. 73, no. 5, pp. 1275–1276, 2020.
  46. . Z. Y. Ding, G. X. Li, L. Chen, C. Shu, J. Song, W. Wang, et al., “Association of Liver Abnormalities with In-Hospital Mortality in Patients with COVID-19,” Journal of Hepatology, vol. 74, no. 6, pp. 1295–1302, 2021.
  47. . N. Ali, “Relationship Between COVID-19 Infection and Liver Injury: A Review of Recent Data,” Frontiers in Medicine, vol. 7, p. 458, 2020.
  48. . X. Y. Zhao, X. X. Xu, H. S. Yin, Q. M. Hu, T. Xiong, Y. Y. Tang, et al., “Clinical Characteristics of Patients with 2019 Coronavirus Disease in a Non-Wuhan Area of Hubei Province, China: A Retrospective Study,” BMC Infectious Diseases, vol. 20, no. 1, pp. 1–8, 2020.
  49. . Q. Cai, D. Huang, P. Ou, H. Yu, Z. Zhu, Z. Xia, et al., “COVID-19 in a Designated Infectious Diseases Hospital Outside Hubei Province, China,” MedRxiv, 2020.
  50. . T. Chen, D. Wu, H. Chen, W. Yan, D. Yang, G. Chen, et al., “Clinical Characteristics of 113 Deceased Patients with Coronavirus Disease 2019: Retrospective Study,” BMJ, vol. 368, 2020.
  51. . I. Garrido, R. Liberal, and G. Macedo, “COVID-19 and Liver Disease—What We Know on 1st May 2020,” Alimentary Pharmacology & Therapeutics, vol. 52, no. 2, pp. 267–275, 2020.
  52. . C. Yeo, S. Kaushal, and D. Yeo, “Enteric Involvement of Coronaviruses: Is Faecal–Oral Transmission of SARS-CoV-2 Possible?” The Lancet Gastroenterology & Hepatology, vol. 5, no. 4, pp. 335–337, 2020.
  53. . C. Zhang, L. Shi, and F.-S. Wang, “Liver Injury in COVID-19: Management and Challenges,” The Lancet Gastroenterology & Hepatology, vol. 5, no. 5, pp. 428–430, 2020.
  54. . U. Boregowda, M. M. Aloysius, A. Perisetti, M. Gajendran, P. Bansal, and H. Goyal, “Serum Activity of Liver Enzymes Is Associated with Higher Mortality in COVID-19: A Systematic Review and Meta-Analysis,” Frontiers in Medicine, vol. 7, p. 431, 2020.
  55. . H. Wu, S. Liu, H. Luo, and M. Chen, “Progress in the Clinical Features and Pathogenesis of Abnormal Liver Enzymes in Coronavirus Disease 2019,” Journal of Clinical and Translational Hepatology, vol. 9, no. 2, pp. 239–245, 2021.
  56. . Q. Cai, D. Huang, H. Yu, Z. Zhu, Z. Xia, Y. Su, et al., “COVID-19: Abnormal Liver Function Tests,” Journal of Hepatology, vol. 73, no. 3, pp. 566–574, 2020.

Downloads

Download data is not yet available.