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

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.

Do COVID-19 patients who receive high-flow nasal cannula have more comorbidities and worse outcomes?

INTRODUCTION: High-flow nasal cannula oxygen therapy (HFNC) has gained attention as an alternative respiratory support for critically ill COVID-19 patients, however, the evidence behind HFNC has been unbalanced as it covers various comorbidities in hypoxic and hypercapnic respiratory failure. We sought to identify what group of patients needed HFNC and to assess whether its use impacted length of stay and survival. METHODS: A retrospective cohort study was performed at a single center urban academic center. Data collected included age, gender, BMI, medical comorbidities, length of hospital stay and mortality for all patients hospitalized with COVID-19. We compared the characteristics of the patients who received HFNC at any point during their hospitalization to all patients hospitalized with COVID-19. RESULTS: The total number of COVID-19 patients was 363. HFNC was used in 115 admitted patients, of which, 74 were in the ICU with a mean length of stay of 7 days. Overall this group had an average hospital length of stay of 15 days in total as opposed to 10.2 days in non-HFNC utilizers. The most common comorbidities seen in the cohort were hypertension (76.4%), diabetes mellitus (37.4%), asthma (14.6%), COPD (11.24%), and obstructive sleep apnea (4.5%). In patients who received HFNC, 41.2% survived compared to 71.8% of all COVID-19 patients. CONCLUSIONS: Factors determining the outcome of patients using HFNC are not well understood. Our patients who received HFNC were more likely to have underlying cardiopulmonary disease than non-HFNC utilizers. Furthermore, they had a longer length of stay and a higher mortality rate in comparison to all COVID-19 patients. While we specifically identified patients who received HFNC, some of these patients received other forms of supplemental oxygen therapy during their hospital stay which may confound the characteristics of this group. It is also possible that patients receiving HFNC were sicker in general, which may explain their disparity in mortality and hospital stay duration. Further research needs to be done in order to clarify if HFNC in COVID-19 patients, particularly those with cardiopulmonary comorbidities, is beneficial in delaying escalation of oxygen therapy and potentially prolonging survival.

Potential biomarkers for severe ards in the setting of SARS-CoV-2 ICU admission

INTRODUCTION: Acute respiratory disease syndrome (ARDS) is due to compromised lung oxygen exchange in the setting of severe alveolar inflammation. This can be assessed and diagnosed using the ratio of alveolar oxygen saturation (PaO2) to the fraction of inspired oxygen (FiO2), P-F ratio. In hospitalized COVID-19 patients, the role of trending inflammatory markers to categorize levels of ARDS severity in the clinical setting has yet to be established. In this study, we describe the correlational relationship of five biomarkers to the PaO2/FiO2 ratio (P-F ratio), a key diagnostic criterion, and a measure of severity in ARDS. METHODS: This is a prospective cohort analysis of SARs-CoV-2 patients admitted to the ICU at a single urban academic center from March to June 2020. Levels of Endotoxin activity assay (EAA), CRP, ferritin, LDH, and d-dimer were obtained from intubated patients throughout their ICU stay. PaO2 and FiO2 values matching the same days as the biomarkers and demographic information were abstracted from the medical record. The inflammatory markers were matched to the P-F ratios of the same day, and Spearman Correlation Coefficients were performed to detect the relationship between them. RESULTS: A total of 45 intubated COVID patients were included, with baseline characteristics of: median age 55 years and 33% female, 62% Black, 27% Hispanic, 9% Asian, and 2% White. Spearman Correlation Coefficient (ρ) showed statistically significant relationships between P/F ratios and EAA, IL-6, CRP, and ESR, with respective values of: ρ (89)=-0.2366, p=0.02;ρ (13)=-0.7143, p=0.006;ρ (77)=-0.3670, p=0.001;ρ (17)=-0.5569, p=0.02. ρ was also calculated between P/F ratios and Ferritin, D-dimer, WBC, and LDH with respective values of: ρ (77)=0.0819, p=0.47;ρ (78)=-0.2105, p=0.06;ρ (88)=-0.1046, p=0.33;ρ (73)=0.0420, p=0.72, showing no statistically significant relationship between these variables. CONCLUSIONS: EAA, IL-6, CRP, and ESR levels had a statistically significant negative correlation with the P-F ratio. Elevations in these biomarkers correlated with worsening P-F ratios, suggesting that they could serve as useful biomarkers to predict ARDS severity. Additional studies are needed to further understand the trend of these biomarkers and validate their clinical use in prognostication in ARDS.