Endotoxemia in Critically Ill Patients with COVID-19

Abstract

<b><i>Introduction:</i></b> Mechanism(s) mediating critical illness in coronavirus disease 2019 (COVID-19) remain unclear. Previous reports demonstrate the existence of endotoxemia in viral infections without superimposed gram-negative bacteremia, but the rate and severity of endotoxemia in critically ill patients with COVID-19 requires further exploration. <b><i>Materials and Methods:</i></b> This is a single-center cross-sectional study of 92 intensive care unit patients diagnosed with COVID-19 pneumonia. Endotoxin activity (EA) was measured in patients that met the following criteria: (1) age ≥18 years and (2) multi-organ dysfunction score &#x3e;9 from March 24, 2020, to June 20, 2020. <b><i>Results:</i></b> A total of 32 patients met the inclusion/exclusion criteria for measurement of EA. The median age of the study cohort was 60 years with a majority male (21/32, 65%) with hypertension (50%). A significant proportion of the patients exhibited either elevated EA in the intermediate range (0.40–0.59 EA units) (10/32, 31%) or high range (≥0.60 EA units) (14/32, 44%) or were nonresponders (NRs, low neutrophil response) to EA (6/32, 19%), with the presence of gram-negative bacteremia only in 2/32 (6%) patients. Low EA was reported in 2/32 patients. NRs (5/6, 83%) and patients with high EA (7/14, 50%) exhibited higher acute kidney injury (AKI) as compared to patients with low/intermediate EA level (1/12, 8.3%). <b><i>Discussion/Conclusion:</i></b> Elevated EA was observed in a large majority of critically ill patients with COVID-19 and multi-organ dysfunction despite a low incidence of concurrent gram-negative bacteremia. While we observed that elevated EA and nonresponsiveness to EA were associated with AKI in critically ill patients with COVID-19, these findings require further validation in larger longitudinal cohorts.