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The responsible mechanisms are commonly virus-specific and often include either over-activated or delayed local interferon responses, which facilitate efficient viral replication in the primary target organ, systemic viral spread, and rapid onset of organ-specific and harmful inflammatory responses. Despite the distinct replication strategies, human infections with SARS-CoV-2 and highly pathogenic avian influenza viruses demonstrate remarkable similarities and differences regarding the mechanisms of immune induction, disease dynamics, as well as the long-term sequelae, which will be discussed in this review. In addition, we will highlight some important lessons about the effectiveness of antiviral and immunomodulatory therapeutic strategies that this pandemic has taught us.<\/jats:p>","DOI":"10.3390\/cells11142198","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:17:10Z","timestamp":1657844230000},"page":"2198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Virus Infection and Systemic Inflammation: Lessons Learnt from COVID-19 and Beyond"],"prefix":"10.3390","volume":"11","author":[{"given":"Aileen","family":"Faist","sequence":"first","affiliation":[{"name":"Institute of Virology, University of Muenster, 48149 Muenster, Germany"},{"name":"CiM-IMPRS, International Max Planck Research School\u2014Molecular Biomedicine, Westfaelische Wilhelms-University Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josua","family":"Janowski","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Muenster, 48149 Muenster, Germany"},{"name":"SP BioSciences Graduate Program, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-1219","authenticated-orcid":false,"given":"Sriram","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Muenster, 48149 Muenster, Germany"},{"name":"EvoPAD Research Training Group 2220, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Hinse","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8064-9146","authenticated-orcid":false,"given":"Duygu Merve","family":"\u00c7al\u0131\u015fkan","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Muenster, 48149 Muenster, Germany"},{"name":"EvoPAD Research Training Group 2220, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Lange","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4490-3052","authenticated-orcid":false,"given":"Stephan","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Muenster, 48149 Muenster, Germany"},{"name":"CiM-IMPRS, International Max Planck Research School\u2014Molecular Biomedicine, Westfaelische Wilhelms-University Muenster, 48149 Muenster, Germany"},{"name":"EvoPAD Research Training Group 2220, University of Muenster, 48149 Muenster, Germany"},{"name":"Interdisciplinary Center for Clinical Research, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8074-7400","authenticated-orcid":false,"given":"Linda","family":"Brunotte","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Muenster, 48149 Muenster, Germany"},{"name":"Interdisciplinary Center for Clinical Research, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2115354119","DOI":"10.1073\/pnas.2115354119","article-title":"Maladaptation after a virus host switch leads to increased activation of the pro-inflammatory NF-\u03baB pathway","volume":"119","author":"Yu","year":"2022","journal-title":"Proc. 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