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Severe flu management: a point of view

Abstract

Annual flu seasons are typically characterized by changes in types and subtypes of influenza, with variations in terms of severity. Despite remarkable improvements in the prevention and management of patients with suspected or laboratory-confirmed diagnosis of influenza, annual seasonal influenza continues to be associated with a high morbidity and mortality. Admission to the intensive care unit is required for patients with severe forms of seasonal influenza infection, with primary pneumonia being present in most of the cases. This review summarizes the most recent knowledge on the diagnosis and treatment strategies in critically ill patients with influenza, focused on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, and supportive measures. The review focuses on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, supportive measures and relevant existing evidence, in order to provide the non-expert clinician a useful overview. An enhanced understanding of current diagnostic and treatment aspects of influenza infection can contribute to improve outcomes and reduce mortality among ICU patients with influenza.

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References

  1. 1.

    Chow EJ, Doyle JD, Uyeki TM (2019) Influenza virus-related critical illness: prevention, diagnosis, treatment. Crit Care 23:214. https://doi.org/10.1186/s13054-019-2491-9

  2. 2.

    Public Health England (2019) PHE guidance on use of antiviral agents for the treatment and prophylaxis of seasonal influenza. Version 10.0. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/833572/PHE_guidance_antivirals_influenza_201920.pdf. Accessed 27 Oct 2019

  3. 3.

    Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, Griffin MR, Metersky ML, Musher DM, Restrepo MI, Whitney CG (2019) Diagnosis and treatment of adults with community-acquired pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 200:e45–e67. https://doi.org/10.1164/rccm.201908-1581ST

  4. 4.

    Uyeki TM, Bernstein HH, Bradley JS, Englund JA, File TM, Fry AM, Gravenstein S, Hayden FG, Harper SA, Hirshon JM, Ison MG, Johnston BL, Knight SL, McGeer A, Riley LE, Wolfe CR, Alexander PE, Pavia AT (2019) Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenzaa. Clin Infect Dis 68:895–902

  5. 5.

    European Centre for Disease Prevention and Control (2019) An agency of the European Union (2019) Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza—review of recent systematic reviews and meta-analyses. https://www.ecdc.europa.eu/en/seasonal-influenza/prevention-and-control/antivirals/neuraminidase-inhibitors. Accessed 27 Oct 2019

  6. 6.

    Uyeki TM, Bernstein HH, Bradley JS, Uyeki TM, Bernstein HH, Bradley JS, Englund JA, File TM, Fry AM, Gravenstein S, Hayden FG, Harper SA, Hirshon JM, Ison MG, Johnston BL, Knight SL, McGeer A, Riley LE, Wolfe CR, Alexander PE, Pavia AT (2019) Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis 68:e1–e47

  7. 7.

    Lee N, Leo YS, Cao B, Chan PK, Kyaw WM, Uyeki TM, Tam WW, Cheung CS, Yung IM, Li H, Gu L, Liu Y, Liu Z, Qu J, Hui DS (2015) Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients. Eur Respir J 45:1642–1652

  8. 8.

    Nichols MK, Andrew MK, Hatchette TF, Ambrose A, Boivin G, Bowie W, Chit A, Dos Santos G, ElSherif M, Green K, Haguinet F, Halperin SA, Ibarguchi B, Johnstone J, Katz K, Lagacé-Wiens P, Langley JM, LeBlanc J, Loeb M, MacKinnon-Cameron D, McCarthy A, McElhaney JE, McGeer A, Poirier A, Powis J, Richardson D, Schuind A, Semret M, Shinde V, Smith S, Smyth D, Stiver G, Taylor G, Trottier S, Valiquette L, Webster D, Ye L, McNeil SA, Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN), the Toronto Invasive Bacterial Diseases Network (TIBDN) (2018) Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: a pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance(SOS Network). Vaccine 36:2166–2175

  9. 9.

    Torres A, Lee N, Cilloniz C, Vila J, Van der Eerden M (2016) Laboratory diagnosis of pneumonia in the molecular age. Eur Respir J 48:1764–1778

  10. 10.

    Chan MC, Lee N, Ngai KL, Leung TF, Chan PK (2014) Clinical and virologic factors associated with reduced sensitivity of rapid influenza diagnostic tests in hospitalized elderly patients and young children. J Clin Microbiol 52:497–501

  11. 11.

    Álvarez-Lerma F, Marín-Corral J, Vila C, Masclans JR, González de Molina FJ, Martín Loeches I, Barbadillo S, Rodríguez A, H1N1 GETGAG/SEMICYUC Study Group (2016) Delay in diagnosis of influenza A (H1N1)pdm09 virus infection in critically ill patients and impact on clinical outcome. Crit Care 20:3337. https://doi.org/10.1186/s13054-016-1512-1

  12. 12.

    Merckx J, Wali R, Schiller I, Caya C, Gore GC, Chartrand C, Dendukuri N, Papenburg J (2017) Diagnostic accuracy of novel and traditional rapid tests for influenza infection compared with reverse transcriptase polymerase chain reaction: a systematic review and meta-analysis. Ann Intern Med 167:394–409

  13. 13.

    Food and Drug Administration (FDA) (2017) Microbiology devices: reclassification of influenza virus antigen detection test systems intended for use directly with clinical specimens. Fed Regist 82:3609–3619

  14. 14.

    Centers for Disease Control (CDC). Rapid influenza diagnostic tests. https://www.cdc.gov/flu/professionals/diagnosis/table-ridt.html. Nucleic acid detection based tests. https://www.cdc.gov/flu/professionals/diagnosis/table-nucleic-acid-detection.html

  15. 15.

    Lee N, Walsh EE, Sander I, Stolper R, Zakar J, Wyffels V, Myers D, Fleischhackl R (2019) Delayed diagnosis of respiratory syncytial virus infections in hospitalized adults: individual patient data, record review analysis and physician survey in the United States. J Infect Dis 220:969–979

  16. 16.

    Azar MM, Landry ML (2018) Detection of influenza A and B viruses and respiratory syncytial virus by use of Clinical Laboratory Improvement Amendments of 1988 (CLIA)-waived point-of-care assays: a paradigm shift to molecular tests. J Clin Microbiol 56:e00367-18. https://doi.org/10.1128/JCM.00367-18

  17. 17.

    Lee JJ, Verbakel JY, Goyder CR, Ananthakumar T, Tan PS, Turner PJ, Hayward G, Van den Bruel A (2019) The clinical utility of point-of-care tests for influenza in ambulatory care: a systematic review and meta-analysis. Clin Infect Dis 69:24–33

  18. 18.

    Ko F, Drews SJ (2017) The impact of commercial rapid respiratory virus diagnostic tests on patient outcomes and health system utilization. Expert Rev Mol Diagn 17:917–931

  19. 19.

    Rappo U, Schuetz AN, Jenkins SG, Calfee DP, Walsh TJ, Wells MT, Hollenberg JP, Glesby MJ (2016) Impact of early detection of respiratory viruses by multiplex PCR assay on clinical outcomes in adult patients. J Clin Microbiol 54:2096–3010

  20. 20.

    Brendish NJ, Malachira AK, Armstrong L, Houghton R, Aitken S, Nyimbili E, Ewings S, Lillie PJ, Clark TW (2017) Routine molecular point-of-care testing for respiratory viruses in adults presenting to hospital with acute respiratory illness (ResPOC): a pragmatic, open-label, randomised controlled trial. Lancet Respir Med 5:401–411

  21. 21.

    Soto M, Sampietro-Colom L, Vilella A, Pantoja E, Asenjo M, Arjona R, Hurtado JC, Trilla A, Alvarez-Martínez MJ, Mira A, Vila J, Marcos MA (2016) Economic impact of a new rapid PCR assay for detecting influenza virus in an emergency department and hospitalized patients. PLoS One 11:e0146620. https://doi.org/10.1371/journal.pone.0146620

  22. 22.

    Lee N, Chan PK, Tam WW, Chan MC, Lui GC, Kwok AK, Ko FW, Ng SS, Yung IM, Wong RY, Hui DS (2016) Virological response to peramivir treatment in adults hospitalised for influenza-associated lower respiratory tract infections. Int J Antimicrob Agents 48:215–219

  23. 23.

    López Roa P, Rodríguez-Sánchez B, Catalán P, Giannella M, Alcalá L, Padilla B, García de Viedma D, Muñoz P, Bouza E (2012) Diagnosis of influenza in intensive care units: lower respiratory tract samples are better than nose-throat swabs. Am J Respir Crit Care Med 186:929–930

  24. 24.

    Lee N, Hurt AC (2018) Neuraminidase inhibitor resistance in influenza: a clinical perspective. Curr Opin Infect Dis 31:520–526

  25. 25.

    Chan PK, Lee N, Joynt GM, Choi KW, Cheung JL, Yeung AC, Lam P, Wong R, Leung BW, So HY, Lam WY, Hui DC (2011) Clinical and virological course of infection with haemagglutinin D222G mutant strain of 2009 pandemic influenza A (H1N1) virus. J Clin Virol 50:320–324

  26. 26.

    Piralla A, Rovida F, Girello A, Premoli M, Mojoli F, Belliato M, Braschi A, Iotti G, Pariani E, Bubba L, Zanetti AR, Baldanti F (2017) Frequency of respiratory virus infections and next-generation analysis of influenza A/H1N1pdm09 dynamics in the lower respiratory tract of patients admitted to the ICU. PLoS One 12:e0178926. https://doi.org/10.1371/journal.pone.0178926

  27. 27.

    Simon B, Pichon M, Valette M, Burfin G, Richard M, Lina B, Josset L (2019) Whole genome sequencing of A(H3N2) influenza viruses reveals variants associated with severity during the 2016-2017 season. Viruses 11:108. https://doi.org/10.3390/v11020108

  28. 28.

    Vasileva D, Badawi A (2019) C-reactive protein as a biomarker of severe H1N1 influenza. Inflam Res 68:39–46

  29. 29.

    Haran JP, Beaudoin FL, Suner S, Lu S (2013) C-reactive protein as a predictor or bacterial infection among patients with an influenza-like illness. Am J Emerg Med 31:137–144

  30. 30.

    Self WH, Grijalva CG, Williams DJ, Woodworth A, Balk RA, Fakhran S, Zhu Y, Courtney DM, Chappell J, Anderson EJ, Qi C, Waterer GW, Trabue C, Bramley AM, Jain S, Edwards KM, Wunderink RG (2016) Procalcitonin as an early marker of the need for invasive respiratory or vasopressor support in adults with community-acquired pneumonia. Chest 150:819–828

  31. 31.

    Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bucher HC, Annane D, Reinhart K, Falsey AR, Branche A, Damas P, Nijsten M, de Lange DW, Deliberato RO, Oliveira CF, Maravić-Stojković V, Verduri A, Beghé B, Cao B, Shehabi Y, Jensen JS, Corti C, van Oers JAH, Beishuizen A, Girbes ARJ, de Jong E, Briel M, Mueller B (2018) Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis 18:95–107

  32. 32.

    Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bucher HC, Bhatnagar N, Annane D, Reinhart K, Branche A, Damas P, Nijsten M, de Lange DW, Deliberato RO, Lima SS, Maravić-Stojković V, Verduri A, Cao B, Shehabi Y, Beishuizen A, Jensen JS, Corti C, Van Oers JA, Falsey AR, de Jong E, Oliveira CF, Beghe B, Briel M, Mueller B (2017) Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 10:CD007498. https://doi.org/10.1002/14651858.cd007498.pub3

  33. 33.

    Branche AR, Walsh EE, Vargas R, Hulbert B, Formica MA, Baran A, Peterson DR, Falsey AR (2015) Serum procalcitonin measurement and viral testing to guide antibiotic use for respiratory infections in hospitalized adults: a randomized controlled trial. J Infect Dis 212:1692–1700

  34. 34.

    Cuquemelle E, Soulis F, Villers D et al (2011) Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Med 37:796–800

  35. 35.

    de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE, Loef BG, Dormans T, van Melsen GC, Kluiters YC, Kemperman H, van den Elsen MJ, Schouten JA, Streefkerk JO, Krabbe HG, Kieft H, Kluge GH, van Dam VC, van Pelt J, Bormans L, Otten MB, Reidinga AC, Endeman H, Twisk JW, van de Garde EMW, de Smet AMGA, Kesecioglu J, Girbes AR, Nijsten MW, de Lange DW (2016) Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 16:819–827

  36. 36.

    Davey RT Jr, Lynfield R, Dwyer DE, Losso MH, Cozzi-Lepri A, Wentworth D, Lane HC, Dewar R, Rupert A, Metcalf JA, Pett SL, Uyeki TM, Bruguera JM, Angus B, Cummins N, Lundgren J, Neaton JD, INSIGHT FLU 002 & 003 Study Groups (2013) The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies. PLoS One 8:e57121. https://doi.org/10.1371/journal.pone.0057121

  37. 37.

    Tang BM, Shojaei M, Teoh S, Meyers A, Ho J, Ball TB, Keynan Y, Pisipati A, Kumar A, Eisen DP, Lai K, Gillett M, Santram R, Geffers R, Schreiber J, Mozhui K, Huang S, Parnell GP, Nalos M, Holubova M, Chew T, Booth D, Kumar A, McLean A, Schughart K (2019) Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection. Nat Commun 10:3422. https://doi.org/10.1038/s41467-019-11249-y

  38. 38.

    Suarez NM, Bunsow E, Falsey AR, Walsh EE, Mejias A, Ramilo O (2015) Superiority of transcriptional profiling over procalcitonin for distinguishing bacterial from viral lower respiratory tract infections in hospitalized adults. J Infect Dis 212:213–222

  39. 39.

    Bhattacharya S, Rosenberg AF, Peterson DR, Grzesik K, Baran AM, Ashton JM, Gill SR, Corbett AM, Holden-Wiltse J, Topham DJ, Walsh EE, Mariani TJ, Falsey AR (2017) Transcriptomic biomarkers to discriminate bacterial from nonbacterial infection in adults hospitalized with respiratory illness. Sci Rep 7:6548. https://doi.org/10.1038/s41598-017-06738-3

  40. 40.

    Yu J, Peterson DR, Baran AM, Bhattacharya S, Wylie TN, Falsey AR, Mariani TJ, Storch GA (2018) Host gene expression in nose and blood for the diagnosis of viral respiratory infection. J Infect Dis 219:1151–1161

  41. 41.

    Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, O’Garra A, Openshaw PJM, MOSAIC Investigators (2018) Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza. Nat Immunol 19:625–635

  42. 42.

    Hui DS, Lee N, Chan PK, Beigel JH (2018) The role of adjuvant immunomodulatory agents for treatment of severe influenza. Antivir Res 150:202–216

  43. 43.

    Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TS, Al Mamun A, Anovadiya AP, Azziz-Baumgartner E, Báez C, Bassetti M, Beovic B, Bertisch B, Bonmarin I, Booy R, Borja-Aburto VH, Burgmann H, Cao B, Carratala J, Denholm JT, Dominguez SR, Duarte PA, Dubnov-Raz G, Echavarria M, Fanella S, Gao Z, Gérardin P, Giannella M, Gubbels S, Herberg J, Iglesias AL, Hoger PH, Hu X, Islam QT, Jiménez MF, Kandeel A, Keijzers G, Khalili H, Knight M, Kudo K, Kusznierz G, Kuzman I, Kwan AM, Amine IL, Langenegger E, Lankarani KB, Leo YS, Linko R, Liu P, Madanat F, Mayo-Montero E, McGeer A, Memish Z, Metan G, Mickiene A, Mikić D, Mohn KG, Moradi A, Nymadawa P, Oliva ME, Ozkan M, Parekh D, Paul M, Polack FP, Rath BA, Rodríguez AH, Sarrouf EB, Seale AC, Sertogullarindan B, Siqueira MM, Skręt-Magierło J, Stephan F, Talarek E, Tang JW, To KK, Torres A, Törün SH, Tran D, Uyeki TM, Van Zwol A, Vaudry W, Vidmar T, Yokota RT, Zarogoulidis P, PRIDE Consortium Investigators, Nguyen-Van-Tam JS (2014) Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med 2:395–404

  44. 44.

    Beigel JH, Bao Y, Beeler J, Manosuthi W, Slandzicki A, Dar SM, Panuto J, Beasley RL, Perez-Patrigeon S, Suwanpimolkul G, Losso MH, McClure N, Bozzolo DR, Myers C, Holley HP Jr, Hoopes J, Lane HC, Hughes MD, Davey RT, IRC003 Study Team (2017) Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial. Lancet Infect Dis 17:1255–1265

  45. 45.

    Nakamura S, Miyazaki T, Izumikawa K, Kakeya H, Saisho Y, Yanagihara K, Miyazaki Y, Mukae H, Kohno S (2017) Efficacy and safety of intravenous peramivir compared with oseltamivir in high-risk patients infected with influenza B and B viruses: a multicenter randomized controlled study. Open Forum Infect Dis 4:ofx129. https://doi.org/10.1093/ofid/ofx129

  46. 46.

    Ariano RE, Sitar DS, Zelenitsky SA, Zarychanski R, Pisipati A, Ahern S, Kanji S, Rello J, Kumar A (2010) Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza. CMAJ 182:357–363

  47. 47.

    Lemaitre F, Luyt CE, Roullet-Renoleau F, Nieszkowska A, Zahr N, Corvol E, Fernandez C, Antignac M, Farinotti R, Combes A (2012) impact of extracorporeal membrane oxygenation and continuous venovenous hemodiafiltration on the pharmacokinetics of oseltamivir carboxylate in critically ill patients with pandemic (H1N1) influenza. Ther Drug Monit 34:171–175

  48. 48.

    To KK, Hung IF, Li IW, Lee KL, Koo CK, Yan WW, Liu R, Ho KY, Chu KH, Watt CL, Luk WK, Lai KY, Chow FL, Mok T, Buckley T, Chan JF, Wong SS, Zheng B, Chen H, Lau CC, Tse H, Cheng VC, Chan KH, Yuen KY (2010) Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis 50:850–859

  49. 49.

    Lee N, Chan PK, Wong CK, Wong KT, Choi KW, Joynt GM, Lam P, Chan MC, Wong BC, Lui GC, Sin WW, Wong RY, Lam WY, Yeung AC, Leung TF, So HY, Yu AW, Sung JJ, Hui DS (2011) Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia. Antivir Ther 16:237–247

  50. 50.

    Lee J, Park JH, Jwa H, Kim YH (2017) Comparison of efficacy of intravenous peramivir and oral oseltamivir for the treatment of influenza: systematic review and meta-analysis. Yonsei Med J 58:778–785

  51. 51.

    Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, Ishida T, Sekino H, Yamada K, Portsmouth S, Kawaguchi K, Shishido T, Arai M, Tsuchiya K, Uehara T, Watanabe A, Baloxavir Marboxil Investigators Group (2018) Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med 379:913–923

  52. 52.

    Uehara T, Hayden FG, Kawaguchi K, Omoto S, Hurt AC, De Jong MD, Hirotsu N, Sugaya N, Lee N, Baba K, Shishido T, Tsuchiya K, Portsmouth S, Kida H (2019) Treatment-emergent influenza variant viruses with reduced baloxavir susceptibility: impact on clinical and virologic outcomes in uncomplicated influenza. J Infect Dis. https://doi.org/10.1093/infdis/jiz244

  53. 53.

    Finberg RW, Lanno R, Anderson D, Fleischhackl R, van Duijnhoven W, Kauffman RS, Kosoglou T, Vingerhoets J, Leopold L (2019) Phase 2b study of pimodivir (JNJ-63623872) as monotherapy or in combination with oseltamivir for treatment of acute uncomplicated seasonal influenza A: TOPAZ trial. J Infect Dis 219:1026–1034

  54. 54.

    Moreno G, Rodríguez A, Reyes LF, Gomez J, Sole-Violan J, Díaz E, Bodí M, Trefler S, Guardiola J, Yébenes JC, Soriano A, Garnacho-Montero J, Socias L, Del Valle Ortíz M, Correig E, Marín-Corral J, Vallverdú-Vidal M, Restrepo MI, Torres A, Martín-Loeches I, GETGAG Study Group (2018) Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study. Intensive Care Med 44:1470–1482

  55. 55.

    Ni YN, Chen G, Sun J, Liang BM, Liang ZA (2019) The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care 23:99. https://doi.org/10.1186/s13054-019-2395-8

  56. 56.

    Martin-Loeches I, Schultz MJ, Vincent JL, Alvarez-Lerma F, Bos LD, Solé-Violán J, Torres A, Rodriguez A (2017) Increased incidence of co-infection in critically ill patients with influenza. Intensive Care Med 43:48–58

  57. 57.

    Martin-Loeches I, Lemiale V, Geoghegan P, McMahon MA, Pickkers P, Soares M, Perner A, Meyhoff TS, Bukan RB, Rello J, Bauer PR, van de Louw A, Taccone FS, Salluh J, Hemelaar P, Schellongowski P, Rusinova K, Terzi N, Mehta S, Antonelli M, Kouatchet A, Klepstad P, Valkonen M, Landburg PP, Barratt-Due A, Bruneel F, Pène F, Metaxa V, Moreau AS, Souppart V, Burghi G, Girault C, Silva UVA, Montini L, Barbier F, Nielsen LB, Gaborit B, Mokart D, Chevret S, Azoulay E, Efraim investigators and the Nine-I study group (2019) Influenza and associated co-infections in critically ill immunosuppressed patients. Crit Care 23:152. https://doi.org/10.1186/s13054-019-2425-6

  58. 58.

    Schauwvlieghe AFAD, Rijnders BJA, Philips N, Verwijs R, Vanderbeke L, Van Tienen C, Lagrou K, Verweij PE, Van de Veerdonk FL, Gommers D, Spronk P, Bergmans DCJJ, Hoedemaekers A, Andrinopoulou ER, van den Berg CHSB, Juffermans NP, Hodiamont CJ, Vonk AG, Depuydt P, Boelens J, Wauters J, Dutch-Belgian Mycosis study group (2018) Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med 6:782–792

  59. 59.

    Torres A, Chalmers JD, Dela Cruz CS, Dominedò C, Kollef M, Martin-Loeches I, Niederman M, Wunderink RG (2019) Challenges in severe community-acquired pneumonia: a point-of-view review. Intensive Care Med 45:159–171

  60. 60.

    Mc Mahon A, Martin-Loeches I (2017) The pharmacological management of severe influenza infection—’existing and emerging therapies’. Expert Rev Clin Pharmacol 10:81–95

  61. 61.

    Torres A, Martín-Loeches I, Menéndez R (2017) Research in community-acquired pneumonia: the next steps. Intensive Care Med 43:1395–1397

  62. 62.

    Martin-Loeches I, Nseir S, Valles J, Artigas A (2013) From ventilator-associated tracheobronchitis to ventilator-associated pneumonia. Réanimation 22:231–237

  63. 63.

    Esquinas AM, Egbert Pravinkumar S, Scala R, Gay P, Soroksky A, Girault C, Han F, Hui DS, Papadakos PJ, Ambrosino N, International NIV Network (2014) Noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review. Eur Respir Rev 23:427–438

  64. 64.

    Rodríguez A, Ferri C, Martin-Loeches I, Díaz E, Masclans JR, Gordo F, Sole-Violán J, Bodí M, Avilés-Jurado FX, Trefler S, Magret M, Moreno G, Reyes LF, Marin-Corral J, Yebenes JC, Esteban A, Anzueto A, Aliberti S, Restrepo MI, Grupo Español de Trabajo Gripe A Grave (GETGAG)/Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) Working Group; 2009–2015 H1N1 SEMICYUC Working Group investigators (2017) Risk factors for noninvasive ventilation failure in critically ill subjects with confirmed influenza infection. Respir Care 62:1307–1315

  65. 65.

    Perner A, Gordon AC, De Backer D, Dimopoulos G, Russell JA, Lipman J, Jensen JU, Myburgh J, Singer M, Bellomo R, Walsh T (2016) Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med 42:1958–1969

  66. 66.

    Simonis FD, Binnekade JM, Braber A, Gelissen HP, Heidt J, Horn J, Innemee G, de Jonge E, Juffermans NP, Spronk PE, Steuten LM, Tuinman PR, Vriends M, de Vreede G, de Wilde RB, Serpa Neto A, Gama de Abreu M, Pelosi P, Schultz MJ (2015) PReVENT–protective ventilation in patients without ARDS at start of ventilation: study protocol for a randomized controlled trial. Trials 16:226. https://doi.org/10.1186/s13063-015-0759-1

  67. 67.

    Esan A, Hess DR, Raoof S, George L, Sessler CN (2010) Severe hypoxemic respiratory failure: part 1—ventilatory strategies. Chest 137:1203–1216

  68. 68.

    Martin-Loeches I, Bos LD, Goligher EC (2017) Will all ARDS patients be receiving mechanical ventilation in 2035? Yes. Intensive Care Med 43:568–569

  69. 69.

    Murias G, Lucangelo U, Blanch L (2016) Patient-ventilator asynchrony. Curr Opin Crit Care 22:53–59

  70. 70.

    Blanch L, Villagra A, Sales B, Montanya J, Lucangelo U, Luján M, García-Esquirol O, Chacón E, Estruga A, Oliva JC, Hernández-Abadia A, Albaiceta GM, Fernández-Mondejar E, Fernández R, Lopez-Aguilar J, Villar J, Murias G, Kacmarek RM (2015) Asynchronies during mechanical ventilation are associated with mortality. Intensive Care Med 41:633–641

  71. 71.

    National Heart, Lung and Blood Institute PETAL Clinical Trials Network, Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC (2019) Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med 380:1997–2008

  72. 72.

    Guérin C, Beuret P, Constantin JM, Bellani G, Garcia-Olivares P, Roca O, Meertens JH, Maia PA, Becher T, Peterson J, Larsson A, Gurjar M, Hajjej Z, Kovari F, Assiri AH, Mainas E, Hasan MS, Morocho-Tutillo DR, Baboi L, Chrétien JM, François G, Ayzac L, Chen L, Brochard L, Mercat A, Investigators of the APRONET Study Group, the REVA Network, the Réseau recherche de la Société Française d’Anesthésie-Réanimation (SFAR-recherche) and the ESICM Trials Group (2018) A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study. Intensive Care Med 44:22–37

  73. 73.

    Zangrillo A, Biondi-Zoccai G, Landoni G, Frati G, Patroniti N, Pesenti A, Pappalardo F (2013) Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO. Crit Care 17:R30. https://doi.org/10.1186/cc12512

  74. 74.

    Sukhal S, Sethi J, Ganesh M, Villablanca PA, Malhotra AK, Ramakrishna H (2017) Extracorporeal membrane oxygenation in severe influenza infection with respiratory failure: a systematic review and meta-analysis. Ann Card Anaesth 20:14–21

  75. 75.

    Centers for Disease Control and Prevention. Prevention strategies for seasonal influenza in healthcare settings. http://www.cdc.gov/flu/professionals/infectioncontrol/healthcaresettings.htm. Accessed 27 Oct 2019

  76. 76.

    World Health Organization (WHO). Infection prevention and control during health care for confirmed, probable, or suspected cases of pandemic (H1N1) 2009 virus infection and influenza‐like illnesses. https://www.who.int/csr/resources/publications/cp150_2009_1612_ipc_interim_guidance_h1n1.pdf?ua=1. Accessed 27 Oct 2019

  77. 77.

    Public Health Agency of Canada. Guidance: infection prevention and control measures for healthcare workers in acute care and long-term care settings. http://www.phac-aspc.gc.ca/nois-sinp/guide/pdf/ac-sa-eng.pdf. Accessed 27 Oct 2019

  78. 78.

    Public Health England (PHE). Seasonal influenza: guidance for adult critical care units. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/635596/adult__seasonal_influenza_critical_care_guidance.pdf. Accessed 27 Oct 2019

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Correspondence to Antoni Torres.

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Conflict of interest

AT is member of the advisory Board of Jansen for pimovidir. NL has previously received honoraria for consultancy work, speaking in educational programs, and/or travel support from: Shionogi Inc., Janssen Inc., Sanofi Pasteur Ltd., F. Hoffmann-La Roche Ltd., Genentech Inc., CIDARA Therapeutics Inc., all outside the submitted work. IL has no conflict of interest to declare. WS has no conflict of interest to declare.

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Torres, A., Loeches, I., Sligl, W. et al. Severe flu management: a point of view. Intensive Care Med (2020). https://doi.org/10.1007/s00134-019-05868-8

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Keywords

  • Influenza
  • ICU
  • Antivirals
  • Corticosteroids
  • Mortality
  • Pneumonia