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Thus, our goal was to analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-\u03b2), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury. Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-\u03b2, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC). Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages were observed in the COVID-19 group compared to both the H1N1 and the CONTROL groups. A different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-CoV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1\/Th17 response and the higher participation of the Th2. Understanding and managing the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.<\/jats:p>","DOI":"10.1038\/s41598-020-75659-5","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T07:02:57Z","timestamp":1603954977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["IL-4\/IL-13 remodeling pathway of COVID-19 lung injury"],"prefix":"10.1038","volume":"10","author":[{"given":"Caroline Busatta","family":"Vaz de Paula","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Luise Viola","family":"de Azevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula Camargo","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineia Alessandra Scaranello","family":"Malaquias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Flavia Ribeiro dos Santos","family":"Miggiolaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarbas","family":"da Silva Motta J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gibran","family":"Avelino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Arianne Panini","family":"do Carmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Baena","family":"Carstens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0310-7164","authenticated-orcid":false,"given":"Lucia","family":"de Noronha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"75659_CR1","unstructured":"CDC Novel H1N1 Flu | CDC Estimates of 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, April 2009\u2013January 16, 2010. https:\/\/www.cdc.gov\/h1n1flu\/estimates\/April_March_13.htm."},{"key":"75659_CR2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.jare.2020.03.005","volume":"24","author":"MA Shereen","year":"2020","unstructured":"Shereen, M. 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