Surveillance Open Access
Like 0



Timely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.


We assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.


Case-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.


Of 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60–79 years aOR 3.0, 95% CI: 2.4–3.8; 80 years 8.3 (6.6–10.5)) and intensive care unit admission (3.8, 95% CI: 3.4–4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90–0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0–48 hours aOR 0.51, 95% CI: 0.45–0.59; 3–4 days 0.59 (0.51–0.67); 5–7 days 0.64 (0.56–0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40–59 years aOR 0.43, 95% CI: 0.28–0.66; 60–79 years 0.50 (0.39–0.63); ≥80 years 0.51 (0.42–0.63)).


NAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.


Article metrics loading...

Loading full text...

Full text loading...



  1. Nair H, Brooks WA, Katz M, Roca A, Berkley JA, Madhi SA, et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet. 2011;378(9807):1917-30. . Available from: http://www.ncbi.nlm.nih.gov/pubmed/22078723 https://doi.org/10.1016/S0140-6736(11)61051-9  PMID: 22078723 
  2. Hayward AC, Fragaszy EB, Bermingham A, Wang L, Copas A, Edmunds WJ, et al. Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study. Lancet Respir Med. 2014;2(6):445-54.  https://doi.org/10.1016/S2213-2600(14)70034-7  PMID: 24717637 
  3. World Health Organization (WHO). Global epidemiological surveillance standards for influenza. Geneva: WHO; 2013. [Accessed: 3 Jan 2023]. Available from: https://apps.who.int/iris/handle/10665/311261
  4. Abraham GM, Morton JB, Saravolatz LD. Baloxavir: A Novel Antiviral Agent in the Treatment of Influenza. Clin Infect Dis. 2020;71(7):1790-4.  https://doi.org/10.1093/cid/ciaa107  PMID: 32020174 
  5. European Medicines Agency (EMA). Xofluza. Amsterdam: EMA. [Accessed: 3 Jan 2023]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/xofluza
  6. European Medicines Agency (EMA). Relenza. Amsterdam: EMA. [Accessed: 3 Jan 2023]. Available from: https://www.ema.europa.eu/en/relenza
  7. European Medicines Agency (EMA). Tamiflu. Amsterdam: EMA. [Accessed: 3 Jan 2023]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/tamiflu
  8. European Medicines Agency (EMA). Influenza vaccines – quality module. Amsterdam: EMA. [Accessed: 3 Jan 2023]. Available from: https://www.ema.europa.eu/en/influenza-vaccines-quality-module
  9. European medicines Agency (EMA). Update of EU recommendations for 2021-2022 seasonal flu vaccine composition. 2021. Amsterdam: EMA. [Accessed: 3 Jan 2023]. Available from: https://www.ema.europa.eu/en/news/update-eu-recommendations-2021-2022-seasonal-flu-vaccine-composition
  10. Hayden FG, Asher J, Cowling BJ, Hurt AC, Ikematsu H, Kuhlbusch K, et al. Reducing influenza virus transmission: the value of antiviral treatment. Clin Infect Dis. 2022;74(3):532-40.  https://doi.org/10.1093/cid/ciab625  PMID: 34245250 
  11. Domínguez A, Romero-Tamarit A, Soldevila N, Godoy P, Jané M, Martínez A, et al. Effectiveness of antiviral treatment in preventing death in severe hospitalised influenza cases over six seasons. Epidemiol Infect. 2018;146(7):799-808.  https://doi.org/10.1017/S0950268818000663  PMID: 29606178 
  12. Duwe SC, Schmidt B, Gärtner BC, Timm J, Adams O, Fickenscher H, et al. Prophylaxis and treatment of influenza: options, antiviral susceptibility, and existing recommendations. GMS Infect Dis. 2021;9:Doc02. PMID: 34113534 
  13. Muthuri SG, Myles PR, Venkatesan S, Leonardi-Bee J, Nguyen-Van-Tam JS. Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009-2010 influenza A(H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients. J Infect Dis. 2013;207(4):553-63.  https://doi.org/10.1093/infdis/jis726  PMID: 23204175 
  14. Liu JW, Lin SH, Wang LC, Chiu HY, Lee JA. Comparison of antiviral agents for seasonal influenza outcomes in healthy adults and children: a systematic review and network meta-analysis. JAMA Netw Open. 2021;4(8):e2119151.  https://doi.org/10.1001/jamanetworkopen.2021.19151  PMID: 34387680 
  15. Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP, et al. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med. 2012;156(7):512-24.  https://doi.org/10.7326/0003-4819-156-7-201204030-00411  PMID: 22371849 
  16. Appiah GD, Chaves SS, Kirley PD, Miller L, Meek J, Anderson E, et al. Increased antiviral treatment among hospitalized children and adults with laboratory-confirmed influenza, 2010-2015. Clin Infect Dis. 2017;64(3):364-7.  https://doi.org/10.1093/cid/ciw745  PMID: 28013261 
  17. Hooiveld M, van de Groep T, Verheij TJ, van der Sande MA, Verheij RA, Tacken MA, et al. Prescription of antiviral drugs during the 2009 influenza pandemic: an observational study using electronic medical files of general practitioners in the Netherlands. BMC Pharmacol Toxicol. 2013;14(1):55.  https://doi.org/10.1186/2050-6511-14-55  PMID: 24143932 
  18. Doshi S, Kamimoto L, Finelli L, Perez A, Reingold A, Gershman K, et al. Description of antiviral treatment among adults hospitalized with influenza before and during the 2009 pandemic: United States, 2005-2009. J Infect Dis. 2011;204(12):1848-56.  https://doi.org/10.1093/infdis/jir648  PMID: 22013219 
  19. Snacken R, Brown C. New developments of influenza surveillance in Europe. Euro Surveill. 2015;20(4):21020.  https://doi.org/10.2807/ese.20.04.21020-en  PMID: 25655056 
  20. Adlhoch C, Gomes Dias J, Bonmarin I, Hubert B, Larrauri A, Oliva Domínguez JA, et al. Determinants of fatal outcome in patients admitted to intensive care units with influenza, European Union 2009-2017. Open Forum Infect Dis. 2019;6(11):ofz462. . Available from: https://www.ncbi.nlm.nih.gov/pubmed/32258201 https://doi.org/10.1093/ofid/ofz462  PMID: 32258201 
  21. European Centre for Disease Prevention and Control (ECDC). Seasonal influenza vaccination and antiviral use in EU/EEA Member States. Stockholm: ECDC, 2018. Available from: https://www.ecdc.europa.eu/en/publications-data/seasonal-influenza-vaccination-antiviral-use-eu-eea-member-states
  22. Katzen J, Kohn R, Houk JL, Ison MG. Early oseltamivir after hospital admission is associated with shortened hospitalization: a 5-year analysis of oseltamivir timing and clinical outcomes. Clin Infect Dis. 2019;69(1):52-8.  https://doi.org/10.1093/cid/ciy860  PMID: 30304487 
  23. Campbell AP, Tokars JI, Reynolds S, Garg S, Kirley PD, Miller L, et al. Influenza antiviral treatment and length of stay. Pediatrics. 2021;148(4):e2021050417.  https://doi.org/http://dx.doi.org/10.1542/peds.2021-050417  https://doi.org/10.1542/peds.2021-050417 
  24. Louie JK, Yang S, Acosta M, Yen C, Samuel MC, Schechter R, et al. Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. Clin Infect Dis. 2012;55(9):1198-204.  https://doi.org/10.1093/cid/cis636  PMID: 22843781 
  25. Groeneveld GH, Marbus SD, Ismail N, de Vries JJC, Schneeberger P, Oosterheert JJ, et al. Effectiveness of oseltamivir in reduction of complications and 30-day mortality in severe seasonal influenza infection. Int J Antimicrob Agents. 2020;56(5):106155.  https://doi.org/10.1016/j.ijantimicag.2020.106155  PMID: 32898685 
  26. Myles P, Nguyen-Van-Tam JS, Semple MG, Brett SJ, Bannister B, Read RC, et al. Differences between asthmatics and nonasthmatics hospitalised with influenza A infection. Eur Respir J. 2013;41(4):824-31.  https://doi.org/10.1183/09031936.00015512  PMID: 22903963 
  27. Olsen SJ, Winn AK, Budd AP, Prill MM, Steel J, Midgley CM, et al. Changes in influenza and other respiratory virus activity during the COVID-19 pandemic - United States, 2020-2021. MMWR Morb Mortal Wkly Rep. 2021;70(29):1013-9.  https://doi.org/10.15585/mmwr.mm7029a1  PMID: 34292924 
  28. Adlhoch C, Mook P, Lamb F, Ferland L, Melidou A, Amato-Gauci AJ, et al. Very little influenza in the WHO European Region during the 2020/21 season, weeks 40 2020 to 8 2021. Euro Surveill. 2021;26(11):2100221.  https://doi.org/10.2807/1560-7917.ES.2021.26.11.2100221  PMID: 33739256 
  29. Clark TW, Beard KR, Brendish NJ, Malachira AK, Mills S, Chan C, et al. Clinical impact of a routine, molecular, point-of-care, test-and-treat strategy for influenza in adults admitted to hospital (FluPOC): a multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2021;9(4):419-29.  https://doi.org/10.1016/S2213-2600(20)30469-0  PMID: 33285143 
  30. Brendish NJ, Malachira AK, Lillie PJ, Clark TW. Neuraminidase inhibitor use in adults presenting to hospital with suspected influenza: A questionnaire-based survey of practice among hospital physicians. Clin Infect Pract. 2021;11:100075.  https://doi.org/10.1016/j.clinpr.2021.100075 
  31. Delgado-Sanz C, Mazagatos-Ateca C, Oliva J, Gherasim A, Larrauri A. Illness severity in hospitalized influenza patients by virus type and subtype, Spain, 2010-2017. Emerg Infect Dis. 2020;26(2):220-8.  https://doi.org/10.3201/eid2602.181732  PMID: 31961295 

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error