The prognostic value of elevated creatine kinase to predict poor outcome in patients with COVID-19 - A systematic review and meta-analysis

Abstract

Background and aims Creatine kinase (CK), a marker of muscle damage, is potentially associated with a more severe COVID-19. In this systematic review and meta-analysis, we aim to evaluate the association between the elevated CK and severity and mortality in COVID-19. Methods We performed a systematic literature search on PubMed, Scopus, and Embase up until January 26, 2020. The main outcome was poor outcome, a composite of mortality and severe COVID-19. Results There are 2471 patients from 14 studies included in this systematic review and meta-analysis. The incidence of elevated CK in this pooled analysis was 17% (11%, 22%) and the incidence of poor outcome in this pooled analysis was 27% (19%, 34%). Elevated CK was associated with poor outcome in patients with COVID-19 (OR 3.01 [2.21, 4.10], p < 0.001; I 2 : 10.2%). The effect estimate did not vary with age (p = 0.610), male (p = 0.449), hypertension (p = 0.490), and diabetes (p = 0.457). Elevated CK has a sensitivity of 0.24 (0.17, 0.32), specificity of 0.91 (0.86, 0.94), PLR of 2.6 (1.9, 3.7), NLR of 0.84 (0.78, 0.90), DOR of 3 (2, 5), and AUC of 0.62 (0.57, 0.66) for predicting poor outcome in patients with COVID-19. In this pooled analysis, elevated CK confers to a 49% probability for poor outcome and a non-elevated CK confers to a 24% probability. Subgroup analysis and univariate meta-regression indicates that the sensitivity and specificity does not vary with age, male, hypertension, and diabetes. Conclusion Elevated CK was associated with increased mortality and severity in patients with COVID-19. PROSPERO CRD42021233435.

Endotheliopathy marked by high von Willebrand factor (vWF) antigen in COVID-19 is associated with poor outcome: a systematic review and meta-analysis

“…Due to hyperinflammatory reaction in the COVID-19-induced cytokine storm, various inflammatory biomarkers, including interleukin (IL), creatine kinase (CK), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, and procalcitonin are frequently found to be elevated. ( Akbar et al, 2021 ; Huang et al, 2020 ; Yonas et al, 2020 ) Interestingly, meta-regression analysis showed that obesity, hypertension, diabetes, and malignancy did not affect the difference in terms of vWF antigen between the two groups. These factors are usually associated with endotheliopathy, nevertheless, the medications used in the patients in the included studies are obscure.…”

Active prescription of low-dose aspirin during or prior to hospitalization and mortality in COVID-19: A systematic review and meta-analysis of adjusted effect estimates

“…(Bianconi et al, 2020;Pavoni et al, 2020) Elevation of inflammatory and coagulation parameters and derangement of various laboratory values are noted in patients with more severe SARS-COV-2 infection, indicating poor prognosis. (Akbar et al, 2021;Huang et al, 2020b) These alteration may lead to cardiac injuries that were strongly associated with mortality. (Martha et al, 2021;Pranata et al, 2020b;Wibowo et al, 2021aWibowo et al, , 2021b As cytokine storm is the underlying mechanism behind multisystem inflammatory process in severe COVID-19, the use of aspirin could theoretically a promising option in improving patients' outcomes and hindering the development of fatal complications, including ARDS, coagulopathy, sepsis, multi-organ dysfunction, and death.…”

CIGB-300 synthetic peptide, an antagonist of CK2 kinase activity, as a treatment for Covid-19. A computational biology approach

“…The phenotypes in the first subnetwork are all associated to HNRNPA1, MATR3 and SQSTM1 genes, and have been also reported as Covid-19 symptoms [62–66]. For example, elevated creatine kinase levels is associated to a poor outcome prediction [62] and persistent fatigue is a common symptom in Covid-19 patients [65].…”

“…The phenotypes in the first subnetwork are all associated to HNRNPA1, MATR3 and SQSTM1 genes, and have been also reported as Covid-19 symptoms [62–66]. For example, elevated creatine kinase levels is associated to a poor outcome prediction [62] and persistent fatigue is a common symptom in Covid-19 patients [65]. As we mentioned MATR3 and SQSTM1 possess phosphosites that were activated in all four phosphoproteomic studies we analyzed, and HNRNPA1 was the node with the highest degree in the PPI network built.…”

“…The second subnetwork groups phenotypes related to respiratory(Exertional dyspnea, difuse alveolar hemorraghe), bleeding (Metrorrhagia, oral cavity bleeding) and coagulation disorders(Disseminated intravascular coagulation). The phenotypes in the first subnetwork are all associated to HNRNPA1, MATR3 and SQSTM1 genes, and have been also reported as Covid-19 symptoms [62][63][64][65][66]. For example, elevated creatine kinase levels is associated to a poor outcome prediction [62] and persistent fatigue is a common symptom in Covid-19 patients [65].…”