{"doi":"10.2337/db20-1260","title":"LTB4-Driven Inflammation and Increased Expression of <i>ALOX5</i>/<i>ACE2</i> During Severe COVID-19 in Individuals With Diabetes","abstract":"Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B4 (LTB4) pathway (ALOX5). We found that diabetes activates the LTB4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19–related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO2) and arterial partial pressure of oxygen/FiO2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB4 is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB4 and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.","journal":"Diabetes","year":2021,"id":166279,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9636,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":691142,"name":"Antônio Fernando Araújo Machado","orcid":"0000-0003-4070-3758","position":1,"is_corresponding":false},{"id":691143,"name":"Thiago Cerqueira‐Silva","orcid":"0000-0003-4534-2509","position":2,"is_corresponding":false},{"id":691144,"name":"Sara Nunes","orcid":"0000-0001-8546-7598","position":3,"is_corresponding":false},{"id":691823,"name":"Márcio Rivison Silva Cruz","orcid":null,"position":4,"is_corresponding":false},{"id":691145,"name":"Jéssica Silva","orcid":"0000-0001-7698-1595","position":5,"is_corresponding":false},{"id":691824,"name":"Reinan Lima Santos","orcid":null,"position":6,"is_corresponding":false},{"id":691146,"name":"Aldina Barral","orcid":"0000-0002-7177-464X","position":7,"is_corresponding":false},{"id":691147,"name":"Pablo Rafael Silveira Oliveira","orcid":"0000-0001-9541-3737","position":8,"is_corresponding":false},{"id":478517,"name":"Ricardo Khouri","orcid":"0000-0001-5664-4436","position":9,"is_corresponding":false},{"id":489990,"name":"C. Henrique Serezani","orcid":"0000-0002-5363-415X","position":10,"is_corresponding":false},{"id":489986,"name":"Cláudia Brodskyn","orcid":"0000-0003-3367-5365","position":11,"is_corresponding":false},{"id":691148,"name":"Juliana Caldas","orcid":"0000-0001-5793-980X","position":12,"is_corresponding":false},{"id":552138,"name":"Manoel Barral‐Netto","orcid":"0000-0002-5823-7903","position":13,"is_corresponding":false},{"id":691149,"name":"Viviane Boaventura","orcid":"0000-0002-7241-6844","position":14,"is_corresponding":false},{"id":489987,"name":"Natália Machado Tavares","orcid":"0000-0002-4026-679X","position":15,"is_corresponding":false},{"id":489988,"name":"Ícaro Bonyek-Silva","orcid":"0000-0002-0346-9360","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:45:45.220559Z","pmid":"34417262","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":[]}