Association of endotoxemia with AKI in critically ill patients with SARS-CoV-2 infection

Background: AKI is frequently complicated by sepsis. Endotoxin (lipopolysaccharide), a component of the outer wall of gram-negative bacteria, has been investigated and acknowledged as one of the triggers of lethal shock during sepsis and drivers of cytokine storm. In studies, septic shock was present in 6.4% patients with severe COVID-19, but blood cultures and respiratory cultures were negative in 76%. Initial cohort study of COVID-19 patients from China showed 4.5% developed AKI, subsequent reports showed higher prevalence. While these data suggest that patients with COVID-19 are at risk for septic shock and AKI, mechanisms mediating these processes in the setting of severe coronavirus 2 (SARS-CoV-2) infection remain unclear. Methods: We conducted a single-center, cross-sectional study in critically ill patients with COVID-19 to test the prevalence of endotoxemia and whether endotoxemia is associated with the development of AKI. Patients were recruited using criteria: Age ≥ 18yr, MODS ≥ 9, sepsis and intensive care unit admission, excluded if pregnant, requiring chronic dialysis or chronic immunosuppressive medications. Blood endotoxin activity (EA) measured in patients who met the criteria using the FDA-approved Endotoxin Activity Assay (EAA). EAA is a chemiluminescent bio-assay based on the oxidative burst reaction of activated neutrophils to complement coated LPS-IgM immune complexes. Patients divided into low (0.0 -0.39 EA units), intermediate (0.40 -0.59 EA units), high (≥ 0.60 EA units), and non-responder (NR) (patients whose neutrophils do not have the ability to respond to preformed immune complexes in the EAA) group based on measurements from the EAA. Results: In this study, endotoxemia observed in 24/32 (75%) of our critically ill patients with COVID-19, despite only 2 patients having positive blood cultures for gramnegative organisms. The incidence of AKI was higher in the high EA group (7/14, 50%) as compared to intermediate EA group (1/10, 10%), p=0.01. The need for renal replacement therapy (RRT) was higher in the elevated EA group (4/14, 29%), with none of the patients in the intermediate group requiring RRT, p=0.008. Conclusions: This study demonstrates the high prevalence of endotoxemia in critically ill patients with COVID-19, regardless of presence of bacteremia. We also observed that high EA was associated with AKI and the need for RRT.