biostudies-literatureEhrlich AAbbottSam and Rina FrankelEuropean Research CouncilNikoh FoundationNIA NIH HHSNHLBI NIH HHSe79946https://www.ebi.ac.uk/biostudies/studies/S-EPMC9937660biostudies-literatureUnknown12<h4>Background</h4>Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention.<h4>Methods</h4>We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran's Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given eLifeEfficacy and safety of metabolic interventions for the treatment of severe COVID-19: in vitro, observational, and non-randomized open-label interventional study.PMC9937660R01 HL157108681870R01 AG074989FENOC0003Ioannidis KAtari NDaskal YKliker LEhrlich ACohen MMaayan SLPavanello CGottlieb AHofree MShafran Tikva SCohen JBShibolet OMandelboim MNasar MRainy NAbu Alkian INahmias YDeutsch LCicero ASirtori CRChirinos JABar-Chaim AHouri IfalseEfficacy and safety of metabolic interventions for the treatment of severe COVID-19: in vitro, observational, and non-randomized open-label interventional study.<h4>Background</h4>Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention.<h4>Methods</h4>We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran's Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given 2023-01-01T00:00:00Z2023 Jan2026-05-28T18:34:35.575Z2024-10-18T18:20:40.899ZS-EPMC99376603670556610.7554/eLife.79946