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Notably, co-infection with other pathogens may worsen the severity of COVID-19 symptoms and increase fatality. Here, we show that co-infection with influenza A virus (IAV) causes more severe body weight loss and more severe and prolonged pneumonia in SARS-CoV-2-infected hamsters. Each virus can efficiently spread in the lungs without interference by the other. However, in immunohistochemical analyses, SARS-CoV-2 and IAV were not detected at the same sites in the respiratory organs of co-infected hamsters, suggesting that either the two viruses may have different cell tropisms in vivo or each virus may inhibit the infection and\/or growth of the other within a cell or adjacent areas in the organs. Furthermore, a significant increase in IL-6 was detected in the sera of hamsters co-infected with SARS-CoV-2 and IAV at 7 and 10\u00a0days post-infection, suggesting that IL-6 may be involved in the increased severity of pneumonia. Our results strongly suggest that IAV co-infection with SARS-CoV-2 can have serious health risks and increased caution should be applied in such cases.<\/jats:p>","DOI":"10.1038\/s41598-021-00809-2","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T10:02:44Z","timestamp":1635415364000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Co-infection of SARS-CoV-2 and influenza virus causes more severe and prolonged pneumonia in hamsters"],"prefix":"10.1038","volume":"11","author":[{"given":"Takaaki","family":"Kinoshita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuteru","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodai","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rokusuke","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"809_CR1","unstructured":"https:\/\/covid19.who.int\/."},{"key":"809_CR2","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1055\/a-1163-7385","volume":"232","author":"G Wehl","year":"2020","unstructured":"Wehl, G., Laible, M. & Rauchenzauner, M. Co-infection of SARS CoV-2 and influenza A in a pediatric patient in Germany. Klin. Padiatr. 232, 217\u2013218 (2020).","journal-title":"Klin. Padiatr."},{"key":"809_CR3","doi-asserted-by":"publisher","first-page":"e128","DOI":"10.1016\/j.jinf.2020.05.041","volume":"81","author":"X Zheng","year":"2020","unstructured":"Zheng, X. et al. Co-infection of SARS-CoV-2 and influenza virus in early stage of the COVID-19 epidemic in, China. J. Infect. 81, e128\u2013e129 (2020).","journal-title":"J. Infect."},{"key":"809_CR4","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.3201\/eid2606.200299","volume":"26","author":"X Wu","year":"2020","unstructured":"Wu, X. et al. Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China. Emerg. Infect. Dis. 26, 1324\u20131326 (2020).","journal-title":"Emerg. Infect. 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