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Patients recovering from influenza pneumonia may experience physical discomfort akin to post-acute sequelae of COVID-19 (PASC). Despite extensive clinical research on viral pneumonia during convalescence, animal model studies are scarce, highlighting the need for a reliable model for pharmaceutical research. In this study, BALB\/c mice were divided into three groups: NC (control), MC (infected with IAV), and Model (treated with oseltamivir post-infection for five days). A fatigue model was then induced in the Model group through diet restriction and weight-bearing swimming. The results showed the MC group had a 75% survival rate, while the NC and Model groups had 100%. Both the MC and Model groups experienced rapid weight loss followed by gradual recovery, differing significantly from the NC group. From dpi (days post-inoculation) 6 to dpi9, the MC group lost more weight than the NC group. The MC group had the highest pulmonary index, but there was no significant difference in IAV Nucleoprotein (NP) expression across groups. The Model group had higher IL-10 levels than the NC and MC groups, while the MC group had the highest TNF-\u03b1 expression. Hematoxylin and eosin (H&amp;E) staining revealed pathological changes in the MC and Model groups, with severe damage and pulmonary fibrosis in the MC group. Oxidative stress markers showed the MC group had the highest lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and lowest superoxide dismutase (SOD) activity. Electron microscopy indicated mitochondrial damage in both the MC and Model groups. The Model group had the lowest splenic and thymic indices, with histological findings showing larger splenic nodules in the MC group and poor thymocyte density and atrophy in the Model group. The successful creation of this mouse model of influenza pneumonia convalescence phase fatigue, exhibiting fatigue syndrome with various symptoms, holds significance for PASC and other viral pneumonia convalescence phase animal model research.<\/jats:p>","DOI":"10.3390\/v17050593","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:24:52Z","timestamp":1745353492000},"page":"593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Establishment and Evaluation of Fatigue Mice Model in the Convalescence Phase of Influenza A"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0307-487X","authenticated-orcid":false,"given":"Xiaoke","family":"Zeng","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road Campus, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road Campus, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road Campus, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Ji","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road Campus, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keying","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road Campus, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9900-3695","authenticated-orcid":false,"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road Campus, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghu","family":"He","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road Campus, Changsha 410208, China"},{"name":"School of Rehabilitation Medicine and Health Care, Hunan University of Medicine, Jinxi Road Campus, Huaihua 418000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S0140-6736(24)01307-2","article-title":"Antivirals for treatment of severe influenza: A systematic review and network meta-analysis of randomised controlled trials","volume":"404","author":"Gao","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.2353\/ajpath.2010.090949","article-title":"Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses","volume":"176","author":"Leijten","year":"2010","journal-title":"Am. 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