Creatine Kinase Levels Not Considered Risk Factor for COVID-19 Post-Acute Sequelae

Nizar Souyah, MD, FAAN

Data from a retrospective chart review analysis of hospitalized encephalopathic patients who developed COVID-19 infection showed that elevated creatine kinase (CK) levels was not a prognostic factor in the development of post-acute sequelae (PASC).¹

Senior author Nizar Souyah, MD, FAAN, an associate professor of pharmacology, physiology, and neuroscience at the Neurological Institute at the Rutgers New Jersey Medical School, and colleagues assessed 43 encephalopathic COVID-19 infected patients, 25 of which had elevated CK levels (E-CK) and 18 considered non-elevated (N-CK). The average serum CK level of each group was 1485 u/L and 87.11 u/L, respectively, with elevated levels defined as anything above 200 u/L.

Presented at the 2023 American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) annual meeting, held November 1-4, in Phoenix, Arizona 14 patients (56%) in the E-CK group and 13 patients (72.22%) in the N-CK group had follow-up at least 4 weeks after admission. Between the 2 groups, there was a similar average total follow-up time (E-CK: 477.37 days; N-CK: 466.7857 days; P >.05). In the follow-up E-CK group, 6 patients (42.85%) reported any 1 of the PASC symptoms whereas in the follow-up N-CK group, 9 patients (69.23%) reported any 1 of the PASC symptoms (rate ratio, 0.73; 95% CI, 0.32-1.69; P = .47).

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Elevated CK level in patents with COVID-19 infection have been shown to correlate with higher mortality. In a 2021 study published in the European Respiratory Journal, results indicated a clear association between CK level and mortality in men and patients with diabetes myelitis (DM). The trial featured 229 patients with COVID-19 without signs of myocardial damage or rhabdomyolysis who were divided based on gender and presence of type 2 DM (89 with DM; 140 without).

Among patients with DM, CK was significantly higher in the deceased group (309 vs 198 u/L; P <.01) and mortality was higher in patients with CK level above the upper limit of normal (UPN; OR, 8.53; CI, 2.45-29.66; P <.01). In men with DM, CK was significantly higher in the deceased group (396 vs 126.5 u/L; P <.01), with mortality higher among those with CK level above the UPN (OR, 7.8; CI, 1.75-34.83; P <.01). In women and normoglycemic patients there was no significant difference in CK level between survived and deceased groups.

Across various research settings, increased CK has been reported among patients with COVID-19. Skeletal muscle injury and myopathies in the setting of COVID-19 have been seen in association with increased neutrophils, lymphopenia, increased C-reactive protein, increased D-dimer levels, length of intensive care unit stay, and more severe disease; however, other studies have linked patient-reported myalgia with more mild disease and reported them as an independent risk factor for improvement.

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REFERENCES
1. Faiz I, Jaffry N, Mandava S, et al. Does elevated creatine kinase increase the risk of developing post-acute sequelae of COVID-19 in encephalopathic COVID-19 patients? Presented at: AANEM 2023; November 1-4; Phoenix, AZ. POSTER 254
2. Kitbalian A, Brovko M, Akulkina L, et al. Association between creatine kinase level and mortality in high-risk patients with COVID-19. European Respiratory Journal. 2021;58:PA650. doi:10.1183/13993003.congress-2021.
3. Friedman SA, Chamchi Z, Silver M, Jacoby N, Perk J, Anziska Y. Skeletal muscle manifestations and creatine kinase in COVID-19. Neurohospitalist. 2022;12(4):597-606. doi:10.1177/19418744221105961