Identification of Biomarkers and Novel Pathways of Alcoholic Liver Disease by Leveraging Metabolomics, Tissue Imaging Mass Spectrometry, and Integrative Machine Learning

Abstract: Theinducesflu-liketreatmenthealth,1,919,430societalpeopleCOVID-19.diseasemeansinfectedextremelyventilators,SARS-CoV-2 . We propose to identify alterations inthe plasma metabolome of patients experiencing different levels of severity of COVID-19. Such changesshould be pivotal in allowing the prediction of the severity of the patient COVID-19 symptoms and also providemechanistic information about the disease and its progression. In addition to our expertise in metabolomics, weare able to carry out this project because we have access to samples from the Yale New Haven HospitalSystem via the IMPACT Biorepository. This repository stores human specimens related to emergingrespiratory viral infections (with a particular focus on COVID-19) in order to support research on factors relatedto viral expression, transmission, disease severity, progression, and susceptibility. The directors of thebiorepository are co-investigators in this supplement. As such, we are in unique position to perform this novelresearch because we have: (a) the infrastructure to conduct the metabolomic analyses and we have alreadydeveloped the methodologies, (b) access to COVID-19 patient plasma samples stored at the IMPACT(Implementing medical and public health actions against coronavirus in Connecticut) Biorepository (andassociated patient records), (c) assembled an extraordinary team that includes expertise in metabolomics,virology, pulmonary and infectious disease, and immunology.of this supplementcurrent pandemic caused by SARS-CoV-2 is of major concern because (i) it is highly contagious, (ii) ita spectrum of adverse health consequences (collectively known as COVID-19) that range from mildsymptoms (fever, chills, cough) to life-endangering pneumonia and SARS, and (iii) there is no effectiveor vaccine to prevent it. To date, the SARS-CoV-2 pandemic has had devastating effects on publicwith an international mortality rate of 5.8% in infected individuals. As of June 6, 2020, the U.S. hascases and a mortality rate of 5.7%. Measures taken to stem the pandemic have paralyzed normal activities and crippled national and international economies. I n the early stages of the pandemic, olderand individuals with specific underlying medical conditions were shown to be more vulnerable toMore recently, it has become apparent that younger, ostensibly healthy individuals likely carry the and may succumb/progress to the more serious manifestations of COVID-19. Currently, there is noto reliably predict the severity of COVID-19 symptoms (or the course of COVID-19) in individualsby SARS-CoV-2 . This represents a significant knowledge deficit. Having such information would behelpful in triaging patients and allowing more efficient utilization of limited health resources, e.g.,ICU beds, and medical personnel. Nor that are associated with the various stages of COVID-19o studies have investigated metabolic alterations caused by