{"doi":"10.1101/2020.06.18.20134353","title":"IL-13 is a driver of COVID-19 severity","abstract":"Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here we report that elevated interleukin-13 (IL-13) was associated with the need for mechanical ventilation in two independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab had less severe disease. In SARS-CoV-2 infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti-IL-13 treatment in infected mice, in the lung, hyaluronan synthase 1 ( Has1 ) was the most downregulated gene and hyaluronan accumulation was decreased. Blockade of the hyaluronan receptor, CD44, reduced mortality in infected mice, supporting the importance of hyaluronan as a pathogenic mediator, and indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and hyaluronan has important implications for therapy of COVID-19 and potentially other pulmonary diseases. <h4>Summary</h4> L-13 levels are elevated in patients with severe COVID-19. In a mouse model of disease, IL-13 neutralization results in reduced disease and lung hyaluronan deposition. Similarly, blockade of hyaluronan’s receptor, CD44, reduces disease, highlighting a novel mechanism for IL-13-mediated pathology.","journal":"medRxiv","year":2020,"id":6437,"datarank":2.2725622498900986,"base_score":4.304065093204169,"endowment":4.304065093204169,"self_citation_contribution":0.6456097639806255,"citation_network_contribution":1.6269524859094733,"self_endowment_contribution":0.6456097639806255,"citer_contribution":1.6269524859094733,"corpus_percentile":null,"corpus_rank":null,"citation_count":73,"citer_count":68,"citers_with_citation_signal":58,"citers_with_endowment":58,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0418,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-06-20","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":59336,"name":"Tara E. 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