**5. Creatinine kinase**

Creatine Kinase (CK) is an intracellular enzyme present primarily in skeletal muscle, myocardium, and brain. Disruption of cell membranes due to hypoxia or other injury releases CK from cytosol to systemic circulation. CK is a dimeric molecule composed of 2 subunits, namely M and B. Combinations of these subunits form the isoenzymes CK-MM, CK-MB, and CK-BB. A significant concentration of CK-MB isoenzyme is found almost exclusively in the myocardium, and therefore elevations in CK-MB levels in serum is highly specific and sensitive for myocardial injury. Normal reference values for CK-MB range from 3 to 5% of total CK, or 5 to 25 IU/L. Creatine Kinase as a marker of myocardial injury has been largely replaced by troponin in clinical practice. As with troponins, several mechanisms explain the elevated cardiac markers in severe COVID-19: viral myocarditis, cytokinedriven myocardial damage, microangiopathy, and unmasked CAD. Myocardial ACE2 receptors are targets for SARS-CoV-2. A hypothesis is that SARS-CoV-2 induces indirect cardiovascular injury through activation of the immune system. The virus attaches to the pattern recognition receptors (PRRs), that initiate hostimmune defense. This host-immune defense system, in turn, induces inflammatory reactance that culminates in a cytokine storm. The cytokine storm is caused by the release of reactive oxygen species (ROS), endogenous nitric oxide (NO), and damage-associated molecular proteins (DAMPs) by the injured myocardium that ultimately leads to myocardial injury. Cytokines and host-immune dysregulation cause direct and indirect cardiac injury, leading to an increase in troponin and CK-MB. A meta-analysis showed that when compared with mortality, COVID-19 patients who died had significantly higher biomarkers, including CK-MB. Another meta-analysis showed that there was a significantly higher CK level in patients who died compared to patients who survived, whereas the patients who were critically ill did not have significantly higher CK levels compared to the patients who were not critically ill.
