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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.

Keywords: CK-MM myalgia persistent myalgia post-COVID-19 syndrome

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
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Aria Adhiatma
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Christrijogo Sumartono Waloejo
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Bambang Pujo Semedi
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Hamzah
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Prihatma Kriswidyatomo
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