{"doi":"10.1093/infdis/jiad536","title":"Severe Acute Respiratory Syndrome Coronavirus 2 Infection Alters Mediators of Lung Tissue Remodeling In Vitro and In Vivo","abstract":"BACKGROUND: Altered mediators of airway tissue remodeling such as matrix metalloproteinases (MMPs) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may contribute to morbidity in coronavirus disease 2019 (COVID-19); however, the differential impact of SARS-CoV-2 variants of concern (VOCs) on MMPs is unknown. METHODS: Using both in vitro human airway cell culture model and in vivo transgenic mouse model of SARS-CoV-2 infection, we studied the differential effect of SARS-CoV-2 VOCs on expression of key MMPs and inflammatory mediators in airway cells and tissues. RESULTS: The most consistent findings with all SARS-CoV-2 variants in infected compared to uninfected human bronchial epithelial cell air-liquid interface cultures were the SARS-CoV-2-induced increases in MMP-12 and tissue inhibitor of MMPs. Infection with both SARS-CoV-2 wild type and SARS-CoV-2 Delta variant over 3 days postinfection (dpi) and with Beta variant over 7 dpi increased lung tissue levels of MMP-9 compared to uninfected mice. Overall, SARS-CoV-2 variants had differential dose-dependent impact on secretion of MMP-1, MMP-2, MMP-9, and MMP-12 that varied at the protein versus the gene level and in the early noninflammatory compared to late inflammatory phase of infection. CONCLUSIONS: We provide novel mechanistic insight that the differential impact of SARS-CoV-2 variants on severity of COVID-19 may partially be attributed to unique changes in MMPs.","journal":"The Journal of Infectious Diseases","year":2023,"id":415099,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.862,"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":1196926,"name":"Chandrima Gain","orcid":"0000-0001-6256-1565","position":1,"is_corresponding":false},{"id":414522,"name":"Madhav Sharma","orcid":"0000-0003-0068-5508","position":2,"is_corresponding":false},{"id":1196927,"name":"Leila Fotooh Abadi","orcid":"0000-0002-6549-4043","position":3,"is_corresponding":false},{"id":750474,"name":"Cristelle Hugo","orcid":null,"position":4,"is_corresponding":false},{"id":1197241,"name":"Hariclea Vassilopoulos","orcid":null,"position":5,"is_corresponding":false},{"id":778131,"name":"Μαρία Δάσκου","orcid":"0000-0002-9431-2528","position":6,"is_corresponding":false},{"id":253658,"name":"Gregory A. Fishbein","orcid":"0000-0002-3632-5654","position":7,"is_corresponding":false},{"id":414531,"name":"Theodoros Kelesidis","orcid":"0000-0002-8463-3811","position":8,"is_corresponding":false},{"id":1171388,"name":"Michael K. Wong","orcid":"0000-0002-4247-738X","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-19T01:22:08.814145Z","pmid":"38109685","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":[]}