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This article reviews how, in the last 100 years, the response to influenza pandemics has gradually evolved from fragmented crisis response to vaccines and direct acting antivirals (DAAs).The first pandemic to make use of mass antiviral prophylaxis and treatment was in 2009. Introduction of DAAs for seasonal influenza management in 1999\/2000 provided a foundation for use in the pandemic response. Lessons from the 2009 pandemic helped inform the response to the COVID-19 pandemic in 2020. DAAs, antibody therapies, and immune modulators may all have a role to play in minimizing the severity of disease from a pandemic virus strain. Rapid clinical studies evaluating potential therapeutic options will likely be necessary; an agile research infrastructure is a crucial element of a pandemic response capability. Preplanning different pandemic influenza scenarios and the likely treatment uncertainties will help maintain healthcare system preparedness.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf307","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T02:27:13Z","timestamp":1760668033000},"page":"S177-S190","source":"Crossref","is-referenced-by-count":6,"title":["Use of Influenza Antivirals in Pandemic Response"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8897-7881","authenticated-orcid":false,"given":"Maria","family":"Zambon","sequence":"first","affiliation":[{"name":"Virus Reference Department, UK Health Security Agency (UKHSA) , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-890X","authenticated-orcid":false,"given":"Puja","family":"Myles","sequence":"additional","affiliation":[{"name":"Clinical Practice Research Datalink (CPRD), Medicines and Healthcare Products Regulatory Agency (MHRA) ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-7414","authenticated-orcid":false,"given":"Norio","family":"Sugaya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keiyu Hospital , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"2025101622265972000_jiaf307-B1","volume-title":"The sweating sickness: a boke or counseill against the disease commonly called the sweate or sweatyng sicknesse","author":"Caius","year":"1552"},{"key":"2025101622265972000_jiaf307-B2","volume-title":"Handbook of geographical and historical pathology. 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