CIRCULATING DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPS) AS PROGNOSTIC MARKERS OF DISEASE SEVERITY IN PATIENTS WITH COVID-19 ARDS IN THE ICU

ABSTRACT

SESSION TITLE Biological Markers in Patients with COVID-19 Posters SESSION TYPE Original Investigation Posters PRESENTED ON 10/18/2022 0130 pm - 0230 pm PURPOSE: Pandemic SARS-CoV-2 infection (COVID-19), like other respiratory viruses, caused a massive incidence of acute respiratory distress syndrome (ARDS). Prior literature showed that influenza infection results in a significant increase in the level of circulating High Mobility Group Box 1 (HMGB1) in infected mice, cotton rats, and in humans;and a small molecule inhibitor of HMGB1 blocked lung pathology and lethality in influenza-infected mice and cotton rats. Moreover, HMGB1 has also been shown to be elevated in the serum of patients with ARDS and is an indicator of increased mortality. Gastrin Releasing Peptide (GRP) has been implicated in bronchopulmonary dysplasia, chronic obstructive pulmonary disease, chronic bronchitis, emphysema, and fibrosis. In addition to HMGB1, GRP represents a novel DAMP that, when targeted therapeutically in influenza-infected mice, is highly protective. The interaction between GRP and HMGB1 is currently under study. We examined if these DAMPS are associated with poor clinical outcomes in patients with COVID-19 ARDS. METHODS: Deidentified patient plasma and serum samples were obtained from discarded, clinical blood samples from 100 patients with COVID-19 admitted to UMMC's intensive care unit (ICU). Demographic and clinical data were collected from the patient’s electronic medical record. HMGB1 and GRP ELISA kits were used to analyze their concentrations in patients’ sera at Day 1 of admission to ICU. Cox proportional hazards models were used to examine the relationship between risk factors and severity of hypoxemia (P/F ratio), need for mechanical ventilation, and need for mechanical circulatory support (VV-ECMO). RESULTS: The average age of study participants was 59.1 years of which 59.2% were men and 57.1% were African American. The mean BMI was 34.3 kg/m2. The prevalence of hypertension, hyperlipidemia, diabetes, pulmonary and cardiovascular disease was 57.1%, 26.5%, 42.9%, 32.7%, and 42.9%, respectively. We found that GRP concentration was associated with worsening hypoxemia (mild 31.9, mod. 42.7, severe 79.0 ng/ml;p=0.014), requirement for mechanical ventilation (No 40.1, Yes 61.5 ng/ml;p=0.063), and need for VV-ECMO (No 48.6, Yes 93.1 ng/ml;p=0.026). HMGB1 concentration was associated with worsening hypoxemia (mild 24.4, mod. 55.1, severe 40.9 ng/ml;p=0.021) but did not correlate with other outcomes. CONCLUSIONS: GRP and HMGB1 have been previously implicated in the pathogenesis of viral infections, such as influenza, and ARDS in animal models and human. Our results suggest that these DAMPs maybe associated with severity of disease in critically ill patients with COVID-19 infection. CLINICAL IMPLICATIONS Future studies should elucidate the specific cellular and biochemical pathways implicated in pathogenesis of ARDS, identify whether HMGB1 and GRP could be potential biomarkers for severe illness outcomes, and test novel anti-HMGB1 and GRP therapeutics in ARDS. DISCLOSURES No relevant relationships by Fahid Alghanim no disclosure on file for Jeffrey Hasday;Consultant relationship with Guidepoint Please note $1-$1000 by Carl Shanholtz, value=Consulting fee stock holder relationship with Teva Pharmaceuticals Please note $1001 - $5000 by Carl Shanholtz, value=stock iinvestor relationship with illumina Please note $1001 - $5000 by Carl Shanholtz, value=options No relevant relationships by Kari Ann Shirey No relevant relationships by Mohan Tulapurkar No relevant relationships by Stefanie Vogel