Faculty Bibliography

RATIONALE Coronavirus Disease-2019(COVID-19), caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2), causes multi-organ failure and death. Metabolic syndrome(MetSyn) characteristics are also risks for COVID-19. The Receptor for Advanced Glycation End-Products(RAGE) is a MetSyn mediator. SARS-CoV via its Spike protein binds ACE2 as its 1o-receptor, and may activate TLR2. Particulate matter(PM) similarly activates an innate immune response, partially via the RAGE receptor, and increases ACE2 expression. Excessive hyaluronan(HA) levels are found in lungs of COVID-19 patients. Reducing HA synthesis and stabilizing the HA shield surrounding cells may be therapeutic. A HA-binding peptide, P15-1, is anti-inflammatory and reduces HA. HA and its binding proteins may provide a link explaining synergistic ACE2 and RAGE signaling, reducing interaction of receptors with their ligands and ultimately inflammation-related changes in peripheral blood mononuclear cells(PBMCs), the severity of which correlate with patient outcome after SARS-CoV-2 exposure. Our focus is to develop novel therapeutic strategies for SARS-CoV-2 inflammation. To begin to explore our HYPOTHESIS that COVID-19 Spike protein and PM co-exposure synergistically induces an inflammatory phenotype and that phenotype can be mitigated by stabilizing the pericellular HA matrix and by inhibiting RAGE. METHODS. We performed in vitro exposure of PBMCs isolated from 9/11 World Trade Center(WTC) 1st- Responders to i. Media alone(MA); ii. WTC PM; iii. SARS-CoV-2 Spike RBD(C19); iv. C19 and PM; v. C19 and P15-1; vi. C19, PM and P15-1 vii. C19, PM and RAGE inhibitor(RAGEInh) FPS-ZM1; viii. LPS(positive control). Total mRNA levels for Cox-2, IL-1beta, IL-6 and MMP-13 24 hours after exposure were analyzed by real time PCR. Comparisons by Student's t- and Mann-Whitney U-tests. Correlations by Spearman's. Significance p<0.05. RESULTS COX-2, IL-1beta, IL-6 and MMP-13 mRNA levels were significantly increased 24-hrs after the administration of PM and C19. Co-exposure to PM and C19 yielded a synergistic increase in the mRNA of IL-beta, Figure 1B. P15-1 and RAGE inhibition significantly reduced mRNA levels of inflammatory markers in primary PBMCs exposed to C19, WTC PM, or a combination of the two, Figure 1. CONCLUSIONS Our work focuses on mitigating the COVID-19 inflammatory phenotype by stabilizing the pericellular HA matrix and by inhibiting RAGE. Preliminary data presented in this abstract will be further explored using PBMCs and cell lines in a multidisciplinary approach

Objective/UNASSIGNED:To determine if oxygen saturation (out-of-hospital SpO2), measured by New York City (NYC) 9-1-1 Emergency Medical Services (EMS), was an independent predictor of coronavirus disease 2019 (COVID-19) in-hospital mortality and length of stay, after controlling for the competing risk of death. If so, out-of-hospital SpO2 could be useful for initial triage. Methods/UNASSIGNED:A population-based longitudinal study of adult patients transported by EMS to emergency departments (ED) between March 5 and April 30, 2020 (the NYC COVID-19 peak period). Inclusion required EMS prehospital SpO2 measurement while breathing room air, transport to emergency department, and a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction test. Multivariable logistic regression modeled mortality as a function of prehospital SpO2, controlling for covariates (age, sex, race/ethnicity, and comorbidities). A competing risk model also was performed to estimate the absolute risks of out-of-hospital SpO2 on the cumulative incidence of being discharged from the hospital alive. Results/UNASSIGNED:In 1673 patients, out-of-hospital SpO2 and age were independent predictors of in-hospital mortality and length of stay, after controlling for the competing risk of death. Among patients ≥66 years old, the probability of death was 26% with an out-of-hospital SpO2 >90% versus 54% with an out-of-hospital SpO2 ≤90%. Among patients <66 years old, the probability of death was 11.5% with an out-of-hospital SpO2 >90% versus 31% with an out-of-hospital SpO2 ≤ 90%. An out-of-hospital SpO2 level ≤90% was associated with over 50% decreased likelihood of being discharged alive, regardless of age. Conclusions/UNASSIGNED:Out-of-hospital SpO2 and age predicted in-hospital mortality and length of stay: An out-of-hospital SpO2 ≤90% strongly supports a triage decision for immediate hospital admission. For out-of-hospital SpO2 >90%, the decision to admit depends on multiple factors, including age, resource availability (outpatient vs inpatient), and the potential impact of new treatments.

BACKGROUND:Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center obstructive airways disease (WTC-OAD). We have designed this study to (1) assess the dietary phenotype (food types, physical activity, and dietary habits) of the Fire Department of New York (FDNY) WTC-Health Program (WTC-HP) cohort and (2) quantify the association of dietary quality and its advanced glycation end product (AGE) content with the development of WTC-OAD. METHODS: < LLN) and/or airway hyperreactivity (AHR; positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version (REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted (7/17/2019). Diet quality [low-(15-19), moderate-(20-29), and high-(30-39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking, hyperglycemia, hypertension, age on 9/11, WTC-exposure, BMI, and job description. RESULTS:N = 9508 completed the annual questionnaire, while N = 4015 completed REAP-S and had spirometry. WTC-OAD developed in N = 921, while N = 3094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats, fried foods, sugary drinks), fewer (vegetables, whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD. CONCLUSIONS:REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.

Risk factors for #COVID19 infection and severe disease (hospitalisation or death) in NYC first responders: greater pre-pandemic rate of FEV₁ decline is associated with severe COVID-19, as is emergency medical service work versus firefighting https://bit.ly/3nZPuZY.