PLASMA LIPIDS AND AMINO ACIDS LINKED TO LOW SARS-CoV-2 SUSCEPTIBILITY

Background: The mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why a subset of unvaccinated individuals remain uninfected despite high-risk exposures. Method(s): We studied an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 ('nonsusceptible') from April to June 2020, who were compared against 'susceptible' individuals to SARS-CoV-2, including uninfected subjects who became infected during the follow-up, and hospitalized patients with different disease severity providing samples at early disease stages. We analyzed plasma samples using different mass spectrometry technique and obtained metabolites and lipids profiles. Result(s): We found that the metabolite profiles were predictive of the selected study groups and identified lipids profiles and metabolites linked to SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, we showed that non-susceptible individuals exhibited unique metabolomics and lipidomic patterns characterized by upregulation of most lipids -especially ceramides and sphingomyelin-and amino acids related to tricarboxylic acid cycle and mitochondrial metabolism, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. Lipids and metabolites pathways analysis revealed that metabolites related to energy production, mitochondrial and tissue dysfunction, and lipids involved in membrane structure and virus infectivity were key markers of SARS-CoV-2 susceptibility. Conclusion(s): Lipid and metabolic profiles differ in 'nonsusceptible' compared to individuals susceptible to SARS-CoV-2. Our study suggests that lipid profiles are relevant actors during SARS-CoV-2 pathogenesis and highlight certain lipids relevant to understand SARS-CoV-2 pathogenesis. (Figure Presented).

THE BEAST IN THE BEAUTY BOX

SESSION TITLE: Critical Care in Chest Infections Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Enterobacter species are notorious for causing nosocomial infection. They were found to be the third most common pathogen in the respiratory tract amongst isolates in the ICU. What makes the situation grim is the growing antibiotic resistance with regards to treating these infections. Such is the extent of this problem that in certain parts of the world the antibiotic sensitivity of Pluralibacter gergoviae is used as an indicator for the spreading antibiotic resistance in the environment. CASE PRESENTATION: A 73 year old female with past medical history significant for hypertension, atrial fibrillation, and Coronary artery disease s/p stent placement in 2019 presented to our facility with a 4 day history of fever, cough and chest discomfort. She had tested positive for COVID-19 two days prior to presentation and was initiated on remdesivir, tocilizumab, and dexamethasone. She was initially managed on the floors but in view of her increasing oxygen requirement she was transferred to the critical care where she was intubated due to respiratory failure. She continued to spike fevers and was persistently hypoxic. Initially this was attributed to COVID pneumonia and a trial of convalescent plasma was also given. After 3 weeks, she tested negative for COVID-19 while still intubated and precautions were taken off. However, she continued to spike fevers. Repeat chest X-ray was done and it showed multifocal airspace disease with increasing opacification in the left upper lobe. Her endotracheal aspirate grew carbapenemase producing Pluralibacter gergoviae sensitive for ciprofloxacin. Subsequently, she was started on IV levofloxacin and received it for a total of 21 days. Her treatment course was complicated by prolonged intubation requiring tracheostomy and development of Pneumatocele. After stopping the antibiotics, she did not have fever and her white blood cell count was within normal limits. DISCUSSION: P. gergoviae is a known contaminant in intravenous fluids, invasive medical devices, eye cream, children's shampoo, skin cream, hand cleaning paste, and cleansing wipes. Over the decades due to selective pressure especially in the cosmetic industry from preservatives it has gained antibiotic resistance via overexpression of detoxifying enzymes, flagellin, modification of membrane structure/function. Improving patient's oral hygiene, implementing infection control protocols strictly in the ICU, minimizing invasive medical devices/catheters and educating the stakeholders shall help in curbing these incidents. Once identified, early Infectious disease specialist involvement can help choose an apt antibiotic regimen on the basis of existing antibiograms. CONCLUSIONS: This case highlighted the importance of close microbiological surveillance, minimizing occurrence of nosocomial infection and treating atypical organisms. Reference #1: Enterobacter gergoviae adaptation to preservatives commonly used in cosmetic industry M. Périamé,J.-M. Pagès,A. Davin-Regli 14 May 2014 DISCLOSURES: No relevant relationships by Abinesh Sekar

A biological rationale for the disparate effects of omega-3 fatty acids on cardiovascular disease outcomes.

The omega-3 fatty acids (n3-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rapidly incorporate into cell membranes where they modulate signal transduction pathways, lipid raft formation, and cholesterol distribution. Membrane n3-FAs also form specialized pro-resolving mediators and other intracellular oxylipins that modulate inflammatory pathways, including T-cell differentiation and gene expression. Cardiovascular (CV) trials have shown that EPA, administered as icosapent ethyl (IPE), reduces composite CV events, along with plaque volume, in statin-treated, high-risk patients. Mixed EPA/DHA regimens have not shown these benefits, perhaps as the result of differences in formulation, dosage, or potential counter-regulatory actions of DHA. Indeed, EPA and DHA have distinct, tissue-specific effects on membrane structural organization and cell function. This review summarizes: (1) results of clinical outcome and imaging trials using n3-FA formulations; (2) membrane interactions of n3-FAs; (3) effects of n3-FAs on membrane oxidative stress and cholesterol crystalline domain formation during hyperglycemia; (4) n3-FA effects on endothelial function; (5) role of n3-FA-generated metabolites in inflammation; and (6) ongoing and future clinical investigations exploring treatment targets for n3-FAs, including COVID-19.

Identification of Potential Inhibitors Against SARS-CoV-2 Using Computational Drug Repurposing Study

Background: SARS-Cov-2 is a newly emerged coronavirus and causes a severe type of pneumonia in the host organism. So, it is an urgent need to find some inhibitors against SARS-Cov-2. Therefore, drug repurposing study is an effective strategy for treating pneumonia to find the inhibitors of SARS-Cov-2 proteins. Methods: For this purpose, a library of 2500 verified drug chemical compounds was generated and the compounds were docked against Nucleocapsid, Membrane and Envelope protein structures of SARS-Cov-2 to determine the binding affinity of the chemical compounds against targeting binding pockets. Moreover, cheminformatics properties and ADMET of these compounds were assessed to find the druglikeness behavior of compounds. The chemical compounds with the lowest S-score were identified as potential inhibitors. Results: Our findings showed that the compound ids 1212, 1019 and 1992 could interact inside the active sites of membrane protein, nucleocapsid protein and envelope protein. Conclusion: This in silico knowledge will be helpful for the design of novel, safe and less expensive drugs against the SARS-Cov-2.

Binding of the small-molecule kinase inhibitor ruxolitinib to membranes does not disturb membrane integrity.

Ruxolitinib is a small-molecule protein kinase inhibitor, which is used as a therapeutic agent against several diseases. Due to its anti-inflammatory impact, ruxolitinib has also been considered recently for usage in the treatment of Covid-19. While the specific effects of ruxolitinib on Janus kinases (JAK) is comparatively well investigated, its (unspecific) impact on membranes has not been studied in detail so far. Therefore, we characterized the interaction of this drug with lipid membranes employing different biophysical approaches. Ruxolitinib incorporates into the glycerol region of lipid membranes causing an increase in disorder of the lipid chains. This binding, however, has only marginal influence on the structure and integrity of membranes as found by leakage and permeation assays.