The Role of Ischemia Modified Albumin in Patients With COVID-19

Endothelial activation and dysfunction are associated with COVID-19 severity. Epidemiological studies suggest that severe cases or deaths due to COVID-19 frequently present with underlying comorbidities, such as advanced age, hypertension, diabetes, and cardiovascular diseases. Endothelial dysfunction, with the subsequent use of the complement, the hypercoagulable state and production of thrombin appears to be the common denominator of varieties of clinical signs and symptoms of COVID-19, which are directly associated with thromboembolic events. Necropsy findings in patients with COVID-19 have shown catastrophic microvascular injury, with pulmonary endotheliitis, thrombosis and angiogenesis being distinct pathophysiological features of the lungs in patients with COVID-19 compared with H1N1 patients and uninfected controls.

Venous thromboembolic disease, which can manifest as Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE), often occurs in patients with severe COVID-19, despite prophylactic anticoagulation. PE has been found in almost 20% of patients, despite having received anticoagulant treatment. In another study, necropsy was performed in 12 patients with COVID-19, of whom were receiving anticoagulants. DVT was detected in 7 (58%) patients, although none of them had a clinical suspicion. PE was the leading cause of death in 4 patients. Venous thrombosis occurs in particularly high rates (14-81%) in critically ill COVID-19 patients admitted to Intensive Care Units (ICU). In fact, PE has been recorded as the most common thrombotic complication in these patients with a frequency of up to 81%. In hospitalized patients with COVID-19, venous thrombosis occurs less frequently (3-21%), while for outpatients there are insufficient data. In addition to DVT, cases of acute ischemia of the upper or lower extremity with a potential need for surgery have also been reported as a less common arterial thrombotic complication in COVID-19.

In addition, acute myocardial ischemia is the most commonly reported cardiovascular complication of COVID-19. The prevalence of myocardial ischemia varies from 7% to 28%. Studies have correlated the increase in troponin in hospitalized patients with a more severe clinical course and worse prognosis.

Ischemic stroke is another common extrapulmonary thromboembolic complication of COVID-19. There are reports of ischemic stroke as the first symptom of infection (appearing especially as a middle cerebral artery thrombosis, even in young patients) and as a complication during hospitalization. In retrospective observational studies, the prevalence of ischemic stroke in this population ranges from 1.3% to 46%. The most likely mechanism of strokes during COVID-19 is considered to be subsequent hypercoagulability and vascular endothelial dysfunction through activation of inflammatory cytokines.

Human serum albumin is a peptide, which consists of 585 amino acids bonded in a specific sequence in humans. The ischemia modified albumin (IMA) molecule was identified in early 2000s, when it was observed that hypoxic-induced ischemia resulted in a modification in the circulating albumin molecule. Under ischemic conditions, the N-terminus of albumin is differentiated, possibly as a result of hypoxia, oxidation, free radicals and energy-dependent changes in membranes. This modification at the N-terminus of albumin can be indirectly evaluated. When cobalt (in vitro) is added to an ischemic sample, normal albumin molecules will bind to it, leaving a small percentage free, while IMA cannot bind to the added cobalt due to its modification at its binding site. Elevated IMA percentages result in more unbound cobalt, which can be detected by the addition of a chromatographic agent, such as dithiothreitol, and evaluated photospectrometrically. The increase of IMA is inversely related to the amount of cobalt, which causes an increase in the colour product. This is the basis of the Albumin Cobalt - Binding test, ACB test.