Endotoxin activity as a marker for disease severity in SARS-CoV-2 patients in the ICU

ABSTRACT

INTRODUCTION: Endotoxin Activity Assay (EAA), which measures the chemiluminescent response of the neutrophils to endotoxin using an anti-endotoxin antibody, has been used to predict mortality in patients with gram-negative sepsis. Recent evidence has shown that this indirect method of endotoxin measurement does not account for other causes that may excite or depress neutrophil activity. We sought to evaluate the levels of EAA in patients with severe COVID-19 infections without bacteremia but rather a systemic inflammatory state and acute respiratory distress syndrome. METHODS: This is a single-center, prospective cohort analysis of SARS-CoV-2-positive patients admitted to the ICU at a single academic hospital, from March to June 2020. EAA levels were obtained from each COVID-positive patient at ICU admission. Demographics, as well as the development of bacteremia on blood culture, were abstracted from medical records. Initial EAA values were categorized into low EAA (<0.4), intermediate EAA (0.41-0.60), high EAA (0.61-0.80), and severely high EAA (>0.80). RESULTS: A total of 78 patients were included in the study, with baseline characteristics as follows mean age 62.9 years, 46% female, with a racial distribution of 72% Black, 15% White, and 4% Asian. Of the 78 COVID-positive patients, only eight were confirmed positive for bacteremia, while the remaining patients had two negative blood cultures. Of the eight bacteremic patients, the EAA level was low in zero patients, intermediate in three, high in four, and severely high in one patient, resulting in 100% of patients with intermediate or higher EAA level. Of the 70 patients without bacteremia, the EAA level was low in 13, intermediate in 10, high in 34, and severely high in 13, resulting in 81.4% of patients with an intermediate or higher EAA level. CONCLUSIONS: Elevated levels of EAA representing significant endotoxemia are frequently observed in nonbacteremic patients with severe SARS-CoV-2 viral infection. The source of the endotoxemia is unidentified. Possible explanations include gut bacterial translocation from the endothelial cell dysfunction that is known to occur with COVID 19 infection, or that EAA is an indicator of a primed neutrophil state. Further investigation of the elevated EAA levels seen in COVID -19 infections is warranted.