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

Association between the levels of muscle-specific creatinine kinase (CK-MM) and the incidence of persistent myalgia in COVID-19 survivors

  • Aria Adhiatma ,
  • Christrijogo Sumartono Waloejo ,
  • Bambang Pujo Semedi ,
  • Hamzah ,
  • Prihatma Kriswidyatomo ,
  • Pudji Lestari ,

Abstract

Introduction: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, may result in musculoskeletal tissue injury and is assumingly regulated through central and peripheral pathways. Muscle-specific creatinine kinase (CK-MM) is a specific biomarker used to indicate the presence of musculoskeletal tissue damage. This study aimed to investigate the correlation between the levels of CK-MM and the incidence of persistent myalgia in patients with post-COVID-19 syndromes.

Methods: A cross-sectional study was conducted among COVID-19 survivors at the Faculty of Medicine and Clinical Pathology Laboratory, Universitas Airlangga, Surabaya from June - August 2022. The degree of pain of the myalgia was assessed using a visual analog scale (VAS), while CK-MM level was measured using a sandwich enzyme-linked immunosorbent assay (ELISA). Pearson correlation test at α=0.05 was used to identify the correlation between the levels of CK-MM and the incidence of persistent myalgia in patients with post-COVID-19 syndromes.

Results: A total of 84 participants were enrolled in the study and half (50%) of them reported persistent myalgia post-COVID-19 recovery. Fatigue was the patients' most common persistent symptom (63%). Of the total 42 patients with persistent myalgia, more than half (56%) had mild pain intensity (VAS score: 1–3), and almost all of them (41 patients) experienced myalgia during the COVID-19 diagnosis. All the patients with post-COVID-19 myalgia had normal levels of CK-MM (mean: 32.7 ng/mL; range: 12–93 ng/mL), suggesting no musculoskeletal tissue damage. Anova test suggested no significant different of CK-MM levels between those with and without myalgia in patients with post-COVID-19 syndromes p=0.054).

Conclusion: There was no significant association between CK-MM levels and the incidence of persistent myalgia in patients with post-COVID-19 syndromes.

References

  1. Madurani KA, Suprapto S, Syahputra MY, Puspita I, Masudi A, Rizqi HD, et al. Review—Recent Development of Detection Methods for Controlling COVID-19 Outbreak. J Electrochem Soc [Internet]. 2021;168(3):37511. Available from: http://dx.doi.org/10.1149/1945-7111/abe9cc
  2. Megasari NLA, Utsumi T, Yamani LN, Juniastuti, Gunawan E, Furukawa K, et al. Seroepidemiological study of SARS-CoV-2 infection in East Java, Indonesia. PLoS One [Internet]. 2021 May 6;16(5):e0251234–e0251234. Available from: https://pubmed.ncbi.nlm.nih.gov/33956869
  3. Andriani I, Utariani A, Hamzah H. Correlation of IL-1β Level and Body Temperature to the Severity of Acute Respiratory Distress Syndrome (ARDS) and Mortality in COVID-19 Patients. Indones J Anesthesiol Reanim [Internet]. 2022;4(1):22. Available from: http://dx.doi.org/10.20473/ijar.v4i12022.22-36
  4. Veterini AS, Semedi BP, Prakoeswa CRS, Tinduh D. The Role of “Robotic Assisted Intensivist” As Solution Of Resources Management In Covid-19 Pandemic Era. Indones J Anesthesiol Reanim [Internet]. 2021;3(1):34. Available from: http://dx.doi.org/10.20473/ijar.v3i12021.34-38
  5. Carfì A, Bernabei R, Landi F, Group GAC 19 PACS. Persistent Symptoms in Patients After Acute COVID-19. JAMA [Internet]. 2020 Aug 11;324(6):603–5. Available from: https://pubmed.ncbi.nlm.nih.gov/32644129
  6. Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re’em Y, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine [Internet]. 2021/07/15. 2021 Aug;38:101019. Available from: https://pubmed.ncbi.nlm.nih.gov/34308300
  7. Maltezou HC, Pavli A, Tsakris A. Post-COVID Syndrome: An Insight on Its Pathogenesis. Vaccines [Internet]. 2021 May 12;9(5):497. Available from: https://pubmed.ncbi.nlm.nih.gov/34066007
  8. Widyadharma IPE, Dewi PR, Wijayanti IAS, Utami DKI. Pain related viral infections: a literature review. Egypt J Neurol psychiatry Neurosurg [Internet]. 2020/11/04. 2020;56(1):105. Available from: https://pubmed.ncbi.nlm.nih.gov/33169060
  9. Dydyk AM, Givler A. Central Pain Syndrome [Internet]. Encyclopedia of Pain. Springer Berlin Heidelberg; p. 336. Available from: http://dx.doi.org/10.1007/978-3-540-29805-2_625
  10. Davido B, Seang S, Tubiana R, de Truchis P. Post-COVID-19 chronic symptoms: a postinfectious entity? Clin Microbiol Infect [Internet]. 2020/07/23. 2020 Nov;26(11):1448–9. Available from: https://pubmed.ncbi.nlm.nih.gov/32712242
  11. Galal I, Hussein AARM, Amin MT, Saad MM, Zayan HEE, Abdelsayed MZ, et al. Determinants of persistent post-COVID-19 symptoms: value of a novel COVID-19 symptom score. Egypt J Bronchol [Internet]. 2021;15(1). Available from: http://dx.doi.org/10.1186/s43168-020-00049-4
  12. Fahriani M, Ilmawan M, Fajar JK, Maliga HA, Frediansyah A, Masyeni S, et al. Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis - A systematic review and meta-analysis. Narra J [Internet]. 2021;1(2). Available from: http://dx.doi.org/10.52225/narraj.v1i2.36
  13. Fajar JK, Ilmawan M, Mamada S, Mutiawati E, Husnah M, Yusuf H, et al. Global prevalence of persistent neuromuscular symptoms and the possible pathomechanisms in COVID-19 recovered individuals: A systematic review and meta-analysis. Narra J [Internet]. 2021;1(3). Available from: http://dx.doi.org/10.52225/narra.v1i3.48
  14. Fernández-de-las-Peñas C, Rodríguez-Jiménez J, Fuensalida-Novo S, Palacios-Ceña M, Gómez-Mayordomo V, Florencio LL, et al. Myalgia as a symptom at hospital admission by severe acute respiratory syndrome coronavirus 2 infection is associated with persistent musculoskeletal pain as long-term post-COVID sequelae: a case-control study. Pain [Internet]. 2021;162(12):2832–40. Available from: http://dx.doi.org/10.1097/j.pain.0000000000002306
  15. Jacobs LG, Gourna Paleoudis E, Lesky-Di Bari D, Nyirenda T, Friedman T, Gupta A, et al. Persistence of symptoms and quality of life at 35 days after hospitalization for COVID-19 infection. PLoS One [Internet]. 2020 Dec 11;15(12):e0243882–e0243882. Available from: https://pubmed.ncbi.nlm.nih.gov/33306721
  16. Tabacof L, Tosto-Mancuso J, Wood J, Cortes M, Kontorovich A, McCarthy D, et al. Post-acute COVID-19 Syndrome Negatively Impacts Physical Function, Cognitive Function, Health-Related Quality of Life, and Participation. Am J Phys Med Rehabil [Internet]. 2022 Jan 1;101(1):48–52. Available from: https://pubmed.ncbi.nlm.nih.gov/34686631
  17. Mutiawati E, Syahrul S, Fahriani M, Fajar JK, Mamada SS, Maliga HA, et al. Global prevalence and pathogenesis of headache in COVID-19: A systematic review and meta-analysis. F1000Research [Internet]. 2020 Nov 12;9:1316. Available from: https://pubmed.ncbi.nlm.nih.gov/33953911
  18. Boissoneault J, Sevel L, Letzen J, Robinson M, Staud R. Biomarkers for Musculoskeletal Pain Conditions: Use of Brain Imaging and Machine Learning. Curr Rheumatol Rep [Internet]. 2017 Jan;19(1):5. Available from: https://pubmed.ncbi.nlm.nih.gov/28144827
  19. Barbe MF, Gallagher S, Popoff SN. Serum Biomarkers as Predictors of Stage of Work-related Musculoskeletal Disorders. J Am Acad Orthop Surg [Internet]. 2013;21(10):644–6. Available from: http://dx.doi.org/10.5435/jaaos-21-10-644
  20. Gold JE, Hallman DM, Hellström F, Björklund M, Crenshaw AG, Djupsjobacka M, et al. Systematic review of biochemical biomarkers for neck and upper-extremity musculoskeletal disorders. Scand J Work Environ & Heal [Internet]. 2015;42(2):103–24. Available from: http://dx.doi.org/10.5271/sjweh.3533
  21. Carp SJ, Barbe MF, Winter KA, Amin M, Barr AE. Inflammatory biomarkers increase with severity of upper-extremity overuse disorders. Clin Sci [Internet]. 2007;112(5):305–14. Available from: http://dx.doi.org/10.1042/cs20060050
  22. Calvo-Lobo C, Becerro-de-Bengoa-Vallejo R, Losa-Iglesias ME, Rodríguez-Sanz D, López-López D, San-Antolín M. Biomarkers and Nutrients in Musculoskeletal Disorders. Nutrients [Internet]. 2021 Jan 20;13(2):283. Available from: https://pubmed.ncbi.nlm.nih.gov/33498342
  23. Ghafouri B, Carlsson A, Holmberg S, Thelin A, Tagesson C. Biomarkers of systemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study. BMC Musculoskelet Disord [Internet]. 2016 May 10;17:206. Available from: https://pubmed.ncbi.nlm.nih.gov/27160764
  24. Baird MF, Graham SM, Baker JS, Bickerstaff GF. Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery. J Nutr Metab [Internet]. 2012/01/11. 2012;2012:960363. Available from: https://pubmed.ncbi.nlm.nih.gov/22288008
  25. Bindoff LA. Muscle disease [Internet]. Clinical Biochemistry: Metabolic and Clinical Aspects. Elsevier; 2014. p. 646–59. Available from: http://dx.doi.org/10.1016/b978-0-7020-5140-1.00033-x
  26. Nagaraju K, Gladue HS, Lundberg IE. Inflammatory Diseases of Muscle and Other Myopathies [Internet]. Kelley and Firestein’s Textbook of Rheumatology. Elsevier; 2017. p. 1461-1488.e5. Available from: http://dx.doi.org/10.1016/b978-0-323-31696-5.00085-1
  27. Huerta-Alardín AL, Varon J, Marik PE. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Crit Care [Internet]. 2004/10/20. 2005 Apr;9(2):158–69. Available from: https://pubmed.ncbi.nlm.nih.gov/15774072
  28. Will Y, McDuffie JE, Olaharski AJ, Jeffy BD. Drug Discovery Toxicology [Internet]. John Wiley & Sons, Inc; 2016. Available from: http://dx.doi.org/10.1002/9781119053248
  29. Samprathi M, Jayashree M. Biomarkers in COVID-19: An Up-To-Date Review. Front Pediatr [Internet]. 2021 Mar 30;8:607647. Available from: https://pubmed.ncbi.nlm.nih.gov/33859967
  30. Shehata RSA, Radwan NA, Bakry HM, Seif Eldin A. Assessment of serum CK-MM level as a bioindicator for work-related musculoskeletal injuries among Emergency hospital workers. Toxicol Ind Health [Internet]. 2022;38(1):11–8. Available from: http://dx.doi.org/10.1177/07482337211042727
  31. Huskisson EC. MEASUREMENT OF PAIN. Lancet [Internet]. 1974;304(7889):1127–31. Available from: http://dx.doi.org/10.1016/s0140-6736(74)90884-8
  32. Downie WW, Leatham PA, Rhind VM, Wright V, Branco JA, Anderson JA. Studies with pain rating scales. Ann Rheum Dis [Internet]. 1978 Aug;37(4):378–81. Available from: https://pubmed.ncbi.nlm.nih.gov/686873
  33. Lo KR, Hurst SM, Atkinson KR, Vandenbogaerde T, Beaven CM, Ingram JR. Development and validation of a sensitive immunoassay for the skeletal muscle isoform of creatine kinase. J Sci Med Sport [Internet]. 2010;13(1):117–9. Available from: http://dx.doi.org/10.1016/j.jsams.2008.08.004
  34. McFarland AJ, Yousuf MS, Shiers S, Price TJ. Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain. Pain reports [Internet]. 2021 Jan 7;6(1):e885–e885. Available from: https://pubmed.ncbi.nlm.nih.gov/33458558
  35. Tosato M, Carfì A, Martis I, Pais C, Ciciarello F, Rota E, et al. Prevalence and Predictors of Persistence of COVID-19 Symptoms in Older Adults: A Single-Center Study. J Am Med Dir Assoc [Internet]. 2021/07/19. 2021 Sep;22(9):1840–4. Available from: https://pubmed.ncbi.nlm.nih.gov/34352201
  36. Pescaru CC, Marițescu A, Costin EO, Trăilă D, Marc MS, Trușculescu AA, et al. The Effects of COVID-19 on Skeletal Muscles, Muscle Fatigue and Rehabilitation Programs Outcomes. Medicina (Kaunas) [Internet]. 2022 Sep 1;58(9):1199. Available from: https://pubmed.ncbi.nlm.nih.gov/36143878
  37. Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (London, England) [Internet]. 2021/05/22. 2021 Oct;53(10):737–54. Available from: https://pubmed.ncbi.nlm.nih.gov/34024217
  38. Kunal S, Madan M, Tarke C, Gautam DK, Kinkar JS, Gupta K, et al. Emerging spectrum of post-COVID-19 syndrome. Postgrad Med J [Internet]. 2021;98(1162):633–43. Available from: http://dx.doi.org/10.1136/postgradmedj-2020-139585
  39. Kato K, Shimizu A. Highly sensitive enzyme immunoassay for human creatine kinase MM and MB isozymes. Clin Chim Acta [Internet]. 1986;158(1):99–108. Available from: http://dx.doi.org/10.1016/0009-8981(86)90120-8
  40. Cohen SP, Wang EJ, Doshi TL, Vase L, Cawcutt KA, Tontisirin N. Chronic pain and infection: mechanisms, causes, conditions, treatments, and controversies. BMJ Med [Internet]. 2022;1(1):e000108. Available from: http://dx.doi.org/10.1136/bmjmed-2021-000108
  41. Kosek E, Clauw D, Nijs J, Baron R, Gilron I, Harris RE, et al. Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system. Pain [Internet]. 2021;162(11):2629–34. Available from: http://dx.doi.org/10.1097/j.pain.0000000000002324

How to Cite

Adhiatma, A., Waloejo, C. S. ., Semedi, B. P. ., Hamzah, Kriswidyatomo, P. ., & Lestari, P. . (2022). Association between the levels of muscle-specific creatinine kinase (CK-MM) and the incidence of persistent myalgia in COVID-19 survivors. Bali Medical Journal, 11(3), 1527–1532. https://doi.org/10.15562/bmj.v11i3.3827

HTML
1

Total
0

Share

Search Panel

Aria Adhiatma
Google Scholar
Pubmed
BMJ Journal


Christrijogo Sumartono Waloejo
Google Scholar
Pubmed
BMJ Journal


Bambang Pujo Semedi
Google Scholar
Pubmed
BMJ Journal


Hamzah
Google Scholar
Pubmed
BMJ Journal


Prihatma Kriswidyatomo
Google Scholar
Pubmed
BMJ Journal


Pudji Lestari
Google Scholar
Pubmed
BMJ Journal