{"doi":"10.1038/s42003-023-04730-4","title":"Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection","abstract":"Abstract Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards anaerobic, glucose-dependent metabolism in CD8 + Tc, NKT, and epithelial cells. Consequently, we found that a strong dysregulation in immunometabolism was tied to increased cellular exhaustion, attenuated effector function, and impaired memory differentiation. Pharmacological inhibition of mitophagy with mdivi-1 reduced excess glucose metabolism, resulting in enhanced generation of SARS-CoV-2- specific CD8 + Tc, increased cytokine secretion, and augmented memory cell proliferation. Taken together, our study provides critical insight regarding the cellular mechanisms underlying the effect of SARS-CoV-2 infection on host immune cell metabolism, and highlights immunometabolism as a promising therapeutic target for COVID-19 treatment.","journal":"Communications Biology","year":2023,"id":336122,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1066526,"name":"Anamaria Morales Alvarez","orcid":"0000-0002-9906-7058","position":1,"is_corresponding":false},{"id":1066527,"name":"Kevin Ezhakunnel","orcid":"0000-0002-6171-474X","position":2,"is_corresponding":false},{"id":1066528,"name":"Andrew Manalo","orcid":"0000-0003-4749-5947","position":3,"is_corresponding":false},{"id":1066529,"name":"Thien-Huong Huynh","orcid":"0000-0003-1335-6762","position":4,"is_corresponding":false},{"id":449040,"name":"Jun‐ichi Abe","orcid":"0000-0001-7439-7774","position":5,"is_corresponding":false},{"id":664675,"name":"Nhat-Tu Le","orcid":"0000-0002-7664-2160","position":6,"is_corresponding":false},{"id":103766,"name":"Daniela Weiskopf","orcid":"0000-0003-2968-7371","position":7,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":8,"is_corresponding":false},{"id":598817,"name":"Daniel S. Lupu","orcid":"0000-0001-8174-5482","position":9,"is_corresponding":false},{"id":711423,"name":"Stephen J. Gardell","orcid":"0000-0002-3798-8230","position":10,"is_corresponding":false},{"id":443736,"name":"Hung Nguyen","orcid":"0000-0001-9416-5137","position":11,"is_corresponding":false},{"id":1066525,"name":"Sanjeev Gurshaney","orcid":"0000-0003-4782-2338","position":0,"is_corresponding":true}],"reference_count":115,"raw_metadata":null,"created_at":"2026-07-19T01:10:17.243221Z","pmid":"37029220","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}