Semin Respir Crit Care Med 2021; 42(06): 771-787
DOI: 10.1055/s-0041-1735491
Review Article

Management of Severe Influenza

Liam S. O'Driscoll
1   Department of Intensive Care Medicine, St. James's University Hospital, Multidisciplinary Intensive Care Research Organization (MICRO), Trinity Centre for Health Sciences, Dublin, Ireland
,
Ignacio Martin-Loeches
1   Department of Intensive Care Medicine, St. James's University Hospital, Multidisciplinary Intensive Care Research Organization (MICRO), Trinity Centre for Health Sciences, Dublin, Ireland
2   Respiratory Medicine, Hospital Clinic, IDIBAPS, Universidad de Barcelona, CIBERes, Barcelona, Spain
› Institutsangaben

Abstract

Influenza infection causes severe illness in 3 to 5 million people annually, with up to an estimated 650,000 deaths per annum. As such, it represents an ongoing burden to health care systems and human health. Severe acute respiratory infection can occur, resulting in respiratory failure requiring intensive care support. Herein we discuss diagnostic approaches, including development of CLIA-waived point of care tests that allow rapid diagnosis and treatment of influenza. Bacterial and fungal coinfections in severe influenza pneumonia are associated with worse outcomes, and we summarize the approach and treatment options for diagnosis and treatment of bacterial and Aspergillus coinfection. We discuss the available drug options for the treatment of severe influenza, and treatments which are no longer supported by the evidence base. Finally, we describe the supportive management and ventilatory approach to patients with respiratory failure as a result of severe influenza in the intensive care unit.



Publikationsverlauf

Artikel online veröffentlicht:
16. Dezember 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Iuliano AD, Roguski KM, Chang HH. et al; Global Seasonal Influenza-associated Mortality Collaborator Network. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 2018; 391 (10127): 1285-1300
  • 2 Kalil AC, Thomas PG. Influenza virus-related critical illness: pathophysiology and epidemiology. Crit Care 2019; 23 (01) 258
  • 3 Martin-Loeches I, Soares M, Torres A. Neces-SARI-ly?. Intensive Care Med 2016; 42 (05) 928-930
  • 4 Sanders CJ, Vogel P, McClaren JL, Bajracharya R, Doherty PC, Thomas PG. Compromised respiratory function in lethal influenza infection is characterized by the depletion of type I alveolar epithelial cells beyond threshold levels. Am J Physiol Lung Cell Mol Physiol 2013; 304 (07) L481-L488
  • 5 Teijaro JR, Walsh KB, Cahalan S. et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011; 146 (06) 980-991
  • 6 Li H, Weng H, Lan C. et al. Comparison of patients with avian influenza A (H7N9) and influenza A (H1N1) complicated by acute respiratory distress syndrome. Medicine (Baltimore) 2018; 97 (12) e0194
  • 7 Mertz D, Lo CK, Lytvyn L, Ortiz JR, Loeb M. FLURISK-INVESTIGATORS. Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis. BMC Infect Dis 2019; 19 (01) 683
  • 8 Fezeu L, Julia C, Henegar A. et al. Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: a systematic review and meta-analysis. Obes Rev 2011; 12 (08) 653-659
  • 9 Martin-Loeches I, Lemiale V, Geoghegan P. et al; Efraim investigators and the Nine-I study group. Influenza and associated co-infections in critically ill immunosuppressed patients. Crit Care 2019; 23 (01) 152
  • 10 Cantan B, Luyt CE, Martin-Loeches I. Influenza infections and emergent viral infections in intensive care unit. Semin Respir Crit Care Med 2019; 40 (04) 488-497
  • 11 Maraví-Poma E, Martin-Loeches I, Regidor E. et al; Grupo Español de Trabajo de Gripe Grave A (SEMICYUC). Severe 2009 A/H1N1v influenza in pregnant women in Spain. Crit Care Med 2011; 39 (05) 945-951
  • 12 Mertz D, Kim TH, Johnstone J. et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ 2013; 347: f5061
  • 13 Mertz D, Geraci J, Winkup J, Gessner BD, Ortiz JR, Loeb M. Pregnancy as a risk factor for severe outcomes from influenza virus infection: a systematic review and meta-analysis of observational studies. Vaccine 2017; 35 (04) 521-528
  • 14 Coleman BL, Fadel SA, Fitzpatrick T, Thomas SM. Risk factors for serious outcomes associated with influenza illness in high- versus low- and middle-income countries: systematic literature review and meta-analysis. Influenza Other Respir Viruses 2018; 12 (01) 22-29
  • 15 Martin-Loeches I, J Schultz M. Vincent JL. et al. Increased incidence of co-infection in critically ill patients with influenza. Intensive Care Med 2017; 43 (01) 48-58
  • 16 Martínez A, Soldevila N, Romero-Tamarit A. et al; Surveillance of Hospitalized Cases of Severe Influenza in Catalonia Working Group. Risk factors associated with severe outcomes in adult hospitalized patients according to influenza type and subtype. PLoS One 2019; 14 (01) e0210353
  • 17 Borgatta B, Pérez M, Rello J. et al; pH1N1 GTEI/SEMICYUC. Elevation of creatine kinase is associated with worse outcomes in 2009 pH1N1 influenza A infection. Intensive Care Med 2012; 38 (07) 1152-1161
  • 18 Public Health England. “PHE guidance on use of antiviral agents for the treatment and prophylaxis of seasonal influenza”. Version 10.0, September 2019. Accessed June 20, 2021 at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/833572/PHE_guidance_antivirals_influenza_201920.pdf
  • 19 European Centre for Disease Prevention and Control. “Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza—review of recent systematic reviews and meta-analyses”. August 2017. Accessed June 20, 2021 at: https://www.ecdc.europa.eu/sites/default/files/documents/Scientific-advice-neuraminidase-inhibitors-2017.pdf
  • 20 Uyeki TM, Bernstein HH, Bradley JS. et al. 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 2019; 68 (06) 895-902
  • 21 Lee N, Leo YS, Cao B. et al. Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients. Eur Respir J 2015; 45 (06) 1642-1652
  • 22 US Centers for Disease Control and Prevention. Influenza antiviral medications: summary for clinicians. 2020 . Accessed June 20, 2021 at: www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
  • 23 Álvarez-Lerma F, Marín-Corral J, Vila C. et al; H1N1 GETGAG/SEMICYUC Study Group. Delay in diagnosis of influenza A (H1N1)pdm09 virus infection in critically ill patients and impact on clinical outcome. Crit Care 2016; 20 (01) 337
  • 24 Gordon A, Videa E, Saborío S. et al. Diagnostic accuracy of a rapid influenza test for pandemic influenza A H1N1. PLoS One 2010; 5 (04) e10364
  • 25 Yang JR, Lo J, Ho YL, Wu HS, Liu MT. Pandemic H1N1 and seasonal H3N2 influenza infection in the human population show different distributions of viral loads, which substantially affect the performance of rapid influenza tests. Virus Res 2011; 155 (01) 163-167
  • 26 Torres A, Loeches IM, Sligl W, Lee N. Severe flu management: a point of view. Intensive Care Med 2020; 46 (02) 153-162
  • 27 López Roa P, Rodríguez-Sánchez B, Catalán P. et al. Diagnosis of influenza in intensive care units: lower respiratory tract samples are better than nose-throat swabs. Am J Respir Crit Care Med 2012; 186 (09) 929-930
  • 28 Food and Drug Administration, HHS. Microbiology devices; Reclassification of influenza virus antigen detection test systems intended for use directly with clinical specimens. Final order. Fed Regist 2017; 82 (08) 3609-3619
  • 29 Azar MM, Landry ML. 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 2018; 56 (07) e00367-e18
  • 30 Gibson J, Schechter-Perkins EM, Mitchell P. et al. Multi-center evaluation of the cobas® Liat® Influenza A/B & RSV assay for rapid point of care diagnosis. J Clin Virol 2017; 95: 5-9
  • 31 Brendish NJ, Malachira AK, Armstrong L. et al. 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 2017; 5 (05) 401-411
  • 32 Berry L, Lansbury L, Gale L, Carroll AM, Lim WS. Point of care testing of Influenza A/B and RSV in an adult respiratory assessment unit is associated with improvement in isolation practices and reduction in hospital length of stay. J Med Microbiol 2020; 69 (05) 697-704
  • 33 Lee JJ, Verbakel JY, Goyder CR. et al. The clinical utility of point-of-care tests for influenza in ambulatory care: a systematic review and meta-analysis. Clin Infect Dis 2019; 69 (01) 24-33
  • 34 Ko F, Drews SJ. The impact of commercial rapid respiratory virus diagnostic tests on patient outcomes and health system utilization. Expert Rev Mol Diagn 2017; 17 (10) 917-931
  • 35 Rappo U, Schuetz AN, Jenkins SG. et al. Impact of early detection of respiratory viruses by multiplex PCR assay on clinical outcomes in adult patients. J Clin Microbiol 2016; 54 (08) 2096-2103
  • 36 Beckmann C, Hirsch HH. Diagnostic performance of near-patient testing for influenza. J Clin Virol 2015; 67: 43-46
  • 37 Busson L, Mahadeb B, De Foor M, Vandenberg O, Hallin M. Contribution of a rapid influenza diagnostic test to manage hospitalized patients with suspected influenza. Diagn Microbiol Infect Dis 2017; 87 (03) 238-242
  • 38 Merckx J, Wali R, Schiller I. et al. 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 2017; 167 (06) 394-409
  • 39 Carbonell R, Moreno G, Martín-Loeches I. et al. Prognostic value of procalcitonin and C-reactive protein in 1608 critically ill patients with severe influenza pneumonia. Antibiotics (Basel) 2021; 10 (04) 350
  • 40 Haran JP, Beaudoin FL, Suner S, Lu S. C-reactive protein as predictor of bacterial infection among patients with an influenza-like illness. Am J Emerg Med 2013; 31 (01) 137-144
  • 41 Gautam S, Cohen AJ, Stahl Y. et al. Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia. Thorax 2020; 75 (11) 974-981
  • 42 Napolitano LM, Angus DC, Uyeki TM. Critically ill patients with influenza A(H1N1)pdm09 virus infection in 2014. JAMA 2014; 311 (13) 1289-1290
  • 43 Simonsen L. The global impact of influenza on morbidity and mortality. Vaccine 1999; 17 (Suppl. 01) S3-S10
  • 44 Bhat N, Wright JG, Broder KR. et al; Influenza Special Investigations Team. Influenza-associated deaths among children in the United States, 2003-2004. N Engl J Med 2005; 353 (24) 2559-2567
  • 45 Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008; 198 (07) 962-970
  • 46 Martín-Loeches I, Sanchez-Corral A, Diaz E. et al; H1N1 SEMICYUC Working Group. Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus. Chest 2011; 139 (03) 555-562
  • 47 Rice TW, Rubinson L, Uyeki TM. et al; NHLBI ARDS Network. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med 2012; 40 (05) 1487-1498
  • 48 Klein EY, Monteforte B, Gupta A. et al. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses 2016; 10 (05) 394-403
  • 49 Sender V, Hentrich K, Henriques-Normark B. Virus-induced changes of the respiratory tract environment promote secondary infections with Streptococcus pneumoniae . Front Cell Infect Microbiol 2021; 11: 643326
  • 50 Martin-Loeches I, van Someren Gréve F, Schultz MJ. Bacterial pneumonia as an influenza complication. Curr Opin Infect Dis 2017; 30 (02) 201-207
  • 51 Pittet LA, Hall-Stoodley L, Rutkowski MR, Harmsen AG. Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae . Am J Respir Cell Mol Biol 2010; 42 (04) 450-460
  • 52 Karwelat D, Schmeck B, Ringel M. et al. Influenza virus-mediated suppression of bronchial Chitinase-3-like 1 secretion promotes secondary pneumococcal infection. FASEB J 2020; 34 (12) 16432-16448
  • 53 Gonzalez-Juarbe N, Riegler AN, Jureka AS. et al. Influenza-induced oxidative stress sensitizes lung cells to bacterial-toxin-mediated necroptosis. Cell Rep 2020; 32 (08) 108062
  • 54 Vasileva D, Badawi A. C-reactive protein as a biomarker of severe H1N1 influenza. Inflamm Res 2019; 68 (01) 39-46
  • 55 Self WH, Grijalva CG, Williams DJ. et al. Procalcitonin as an early marker of the need for invasive respiratory or vasopressor support in adults with community-acquired pneumonia. Chest 2016; 150 (04) 819-828
  • 56 Pfister R, Kochanek M, Leygeber T. et al. Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1 influenza pandemic: a prospective cohort study, systematic review and individual patient data meta-analysis. Crit Care 2014; 18 (02) R44
  • 57 Self WH, Balk RA, Grijalva CG. et al. Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia. Clin Infect Dis 2017; 65 (02) 183-190
  • 58 Cuquemelle E, Soulis F, Villers D. et al; A/H1N1 REVA-SRLF Study Group. Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Med 2011; 37 (05) 796-800
  • 59 de Jong E, van Oers JA, Beishuizen A. et al. 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 2016; 16 (07) 819-827
  • 60 Waterer GW, Wunderink RG. The influence of the severity of community-acquired pneumonia on the usefulness of blood cultures. Respir Med 2001; 95 (01) 78-82
  • 61 van der Eerden MM, Vlaspolder F, de Graaff CS, Groot T, Jansen HM, Boersma WG. Value of intensive diagnostic microbiological investigation in low- and high-risk patients with community-acquired pneumonia. Eur J Clin Microbiol Infect Dis 2005; 24 (04) 241-249
  • 62 Strålin K, Törnqvist E, Kaltoft MS, Olcén P, Holmberg H. Etiologic diagnosis of adult bacterial pneumonia by culture and PCR applied to respiratory tract samples. J Clin Microbiol 2006; 44 (02) 643-645
  • 63 Rello J, Lisboa T, Lujan M. et al; DNA-Neumococo Study Group. Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest 2009; 136 (03) 832-840
  • 64 Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev 2011; 20 (121) 156-174
  • 65 Schauwvlieghe AFAD, Rijnders BJA, Philips N. et al; Dutch-Belgian Mycosis study group. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med 2018; 6 (10) 782-792
  • 66 Blot SI, Taccone FS, Van den Abeele AM. et al; AspICU Study Investigators. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med 2012; 186 (01) 56-64
  • 67 Coste A, Frérou A, Raute A. et al. The extent of aspergillosis in critically ill patients with severe influenza pneumonia: a multicenter cohort study. Crit Care Med 2021; 49 (06) 934-942
  • 68 Donnelly JP, Chen SC, Kauffman CA. et al; Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 2020; 71 (06) 1367-1376
  • 69 Hamam J, Navellou JC, Bellanger AP. et al; Collaborative RESSIF group. New clinical algorithm including fungal biomarkers to better diagnose probable invasive pulmonary aspergillosis in ICU. Ann Intensive Care 2021; 11 (01) 41
  • 70 Verweij PE, Rijnders BJA, Brüggemann RJM. et al. Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion. Intensive Care Med 2020; 46 (08) 1524-1535
  • 71 Ullmann AJ, Aguado JM, Arikan-Akdagli S. et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect 2018; 24 (Suppl. 01) e1-e38
  • 72 Vanderbeke L, Janssen NAF, Bergmans DCJJ. et al; Dutch-Belgian Mycosis Study Group. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial. Intensive Care Med 2021; 47 (06) 674-686
  • 73 Patterson TF, Thompson III GR, Denning DW. et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63 (04) e1-e60
  • 74 O'Sullivan S, Torres A, Rodriguez A, Martin-Loeches I. Influenza management with new therapies. Curr Opin Pulm Med 2020; 26 (03) 215-221
  • 75 Behzadi MA, Leyva-Grado VH. Overview of current therapeutics and novel candidates against influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus infections. Front Microbiol 2019; 10: 1327
  • 76 Yamashita M. Laninamivir and its prodrug, CS-8958: long-acting neuraminidase inhibitors for the treatment of influenza. Antivir Chem Chemother 2010; 21 (02) 71-84
  • 77 Aoki FY, Macleod MD, Paggiaro P. et al; IMPACT Study Group. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003; 51 (01) 123-129
  • 78 Louie JK, Yang S, Acosta M. et al. Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. Clin Infect Dis 2012; 55 (09) 1198-1204
  • 79 Shim SJ, Chan M, Owens L, Jaffe A, Prentice B, Homaira N. Rate of use and effectiveness of oseltamivir in the treatment of influenza illness in high-risk populations: a systematic review and meta-analysis. Health Sci Rep 2021; 4 (01) e241
  • 80 Muthuri SG, Venkatesan S, Myles PR. et al; PRIDE Consortium Investigators. 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 2014; 2 (05) 395-404
  • 81 Resche-Rigon M, Azoulay E, Chevret S. Evaluating mortality in intensive care units: contribution of competing risks analyses. Crit Care 2006; 10 (01) R5
  • 82 Wolkewitz M, Schumacher M. Survival biases lead to flawed conclusions in observational treatment studies of influenza patients. J Clin Epidemiol 2017; 84: 121-129
  • 83 Moreno G, Rodríguez A, Sole-Violán J. et al. Early oseltamivir treatment improves survival in critically ill patients with influenza pneumonia. ERJ Open Res 2021; 7 (01) 00888
  • 84 Marty FM, Vidal-Puigserver J, Clark C. et al. Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial. Lancet Respir Med 2017; 5 (02) 135-146
  • 85 Arabi YM, Fowler R, Hayden FG. Critical care management of adults with community-acquired severe respiratory viral infection. Intensive Care Med 2020; 46 (02) 315-328
  • 86 Shie JJ, Fang JM. Development of effective anti-influenza drugs: congeners and conjugates—a review. J Biomed Sci 2019; 26 (01) 84
  • 87 Higashiguchi M, Matsumoto T, Fujii T. A meta-analysis of laninamivir octanoate for treatment and prophylaxis of influenza. Antivir Ther 2018; 23 (02) 157-165
  • 88 Lytras T, Mouratidou E, Andreopoulou A, Bonovas S, Tsiodras S. Effect of early oseltamivir treatment on mortality in critically ill patients with different types of influenza: a multiseason cohort study. Clin Infect Dis 2019; 69 (11) 1896-1902
  • 89 Behillil S, May F, Fourati S. et al. Oseltamivir resistance in severe influenza A(H1N1)pdm09 pneumonia and acute respiratory distress syndrome: a French Multicenter Observational Cohort Study. Clin Infect Dis 2020; 71 (04) 1089-1091
  • 90 Centers for Disease Control and Prevention (CDC). CDC Recommends against the Use of Amantadine and Rimantadine for the Treatment or Prophylaxis of Influenza in the United States during the 2005–06 Influenza Season. CDC health alert. Jan 14, 2006. Accessed June 20, 2021 at: https://web.archive.org/web/20080503092840/http://www.cdc.gov/flu/han011406.htm
  • 91 Meijer A, Lackenby A, Hungnes O. et al; European Influenza Surveillance Scheme. Oseltamivir-resistant influenza virus A (H1N1), Europe, 2007-08 season. Emerg Infect Dis 2009; 15 (04) 552-560
  • 92 Stevaert A, Naesens L. The influenza virus polymerase complex: an update on its structure, functions, and significance for antiviral drug design. Med Res Rev 2016; 36 (06) 1127-1173
  • 93 Shirley M. Baloxavir Marboxil: a review in acute uncomplicated influenza. Drugs 2020; 80 (11) 1109-1118
  • 94 Hayden FG, Sugaya N, Hirotsu N. et al; Baloxavir Marboxil Investigators Group. Baloxavir Marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med 2018; 379 (10) 913-923
  • 95 Ison MG, Portsmouth S, Yoshida Y. et al. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis 2020; 20 (10) 1204-1214
  • 96 Tejada S, Tejo AM, Peña-López Y, Forero CG, Corbella X, Rello J. Neuraminidase inhibitors and single dose baloxavir are effective and safe in uncomplicated influenza: a meta-analysis of randomized controlled trials. Expert Rev Clin Pharmacol 2021; 26: 1-18
  • 97 Taieb V, Ikeoka H, Wojciechowski P. et al. Efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors in the treatment of influenza virus infection in high-risk and uncomplicated patients—a Bayesian network meta-analysis. Curr Med Res Opin 2021; 37 (02) 225-244
  • 98 Kuo YC, Lai CC, Wang YH, Chen CH, Wang CY. Clinical efficacy and safety of baloxavir marboxil in the treatment of influenza: A systematic review and meta-analysis of randomized controlled trials. J Microbiol Immunol Infect 2021; DOI: 10.1016/j.jmii.2021.04.002.
  • 99 Young B, Tan TT, Leo YS. The place for remdesivir in COVID-19 treatment. Lancet Infect Dis 2021; 21 (01) 20-21
  • 100 Baker J, Block SL, Matharu B. et al. Baloxavir Marboxil single-dose treatment in influenza-infected children: a randomized, double-blind, active controlled phase 3 safety and efficacy trial (miniSTONE-2). Pediatr Infect Dis J 2020; 39 (08) 700-705
  • 101 US Food and Drug Administration (FDA). FDA Expands Approval of Influenza Treatment to Post-Exposure Prevention. FDA News Release of November 23, 2020. Accessed June 20, 2021 at: https://www.fda.gov/news-events/press-announcements/fda-expands-approval-influenza-treatment-post-exposure-prevention
  • 102 Ikematsu H, Hayden FG, Kawaguchi K. et al. Baloxavir Marboxil for prophylaxis against influenza in household contacts. N Engl J Med 2020; 383 (04) 309-320
  • 103 Omoto S, Speranzini V, Hashimoto T. et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci Rep 2018; 8 (01) 9633
  • 104 Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad, Ser B, Phys Biol Sci 2017; 93 (07) 449-463
  • 105 Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res 2013; 100 (02) 446-454
  • 106 Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther 2020; 209: 107512
  • 107 Kiso M, Takahashi K, Sakai-Tagawa Y. et al. T-705 (favipiravir) activity against lethal H5N1 influenza A viruses. Proc Natl Acad Sci U S A 2010; 107 (02) 882-887
  • 108 Sangawa H, Komeno T, Nishikawa H. et al. Mechanism of action of T-705 ribosyl triphosphate against influenza virus RNA polymerase. Antimicrob Agents Chemother 2013; 57 (11) 5202-5208
  • 109 Wang Y, Fan G, Salam A. et al. Comparative effectiveness of combined favipiravir and oseltamivir therapy versus oseltamivir monotherapy in critically ill patients with influenza virus infection. J Infect Dis 2020; 221 (10) 1688-1698
  • 110 Ormond L, Liu P, Matuszewski S. et al. The combined effect of oseltamivir and favipiravir on influenza A virus evolution. Genome Biol Evol 2017; 9 (07) 1913-1924
  • 111 Hayden FG, Shindo N. Influenza virus polymerase inhibitors in clinical development. Curr Opin Infect Dis 2019; 32 (02) 176-186
  • 112 Clark MP, Ledeboer MW, Davies I. et al. Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J Med Chem 2014; 57 (15) 6668-6678
  • 113 Byrn RA, Jones SM, Bennett HB. et al. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit. Antimicrob Agents Chemother 2015; 59 (03) 1569-1582
  • 114 Patel MC, Chesnokov A, Jones J. et al. Susceptibility of widely diverse influenza a viruses to PB2 polymerase inhibitor pimodivir. Antiviral Res 2021; 188: 105035
  • 115 Trevejo JM, Asmal M, Vingerhoets J. et al. Pimodivir treatment in adult volunteers experimentally inoculated with live influenza virus: a Phase IIa, randomized, double-blind, placebo-controlled study. Antivir Ther 2018; 23 (04) 335-344
  • 116 Finberg RW, Lanno R, Anderson D. et al. 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 2019; 219 (07) 1026-1034
  • 117 Gregor J, Radilová K, Brynda J, Fanfrlík J, Konvalinka J, Kožíšek M. Structural and thermodynamic analysis of the resistance development to pimodivir (VX-787), the clinical inhibitor of cap binding to PB2 subunit of influenza A polymerase. Molecules 2021; 26 (04) 1007
  • 118 Fechter P, Mingay L, Sharps J, Chambers A, Fodor E, Brownlee GG. Two aromatic residues in the PB2 subunit of influenza A RNA polymerase are crucial for cap binding. J Biol Chem 2003; 278 (22) 20381-20388
  • 119 Tang BM, Craig JC, Eslick GD, Seppelt I, McLean AS. Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med 2009; 37 (05) 1594-1603
  • 120 Webb SA, Pettilä V, Seppelt I. et al; ANZIC Influenza Investigators. Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 2009; 361 (20) 1925-1934
  • 121 Kumar A, Zarychanski R, Pinto R. et al; Canadian Critical Care Trials Group H1N1 Collaborative. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 2009; 302 (17) 1872-1879
  • 122 Diaz E, Martin-Loeches I, Canadell L. et al; H1N1 SEMICYUC-CIBERES-REIPI Working Group (GETGAG). Corticosteroid therapy in patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza. J Infect 2012; 64 (03) 311-318
  • 123 Brun-Buisson C, Richard JC, Mercat A, Thiébaut AC, Brochard L. REVA-SRLF A/H1N1v 2009 Registry Group. Early corticosteroids in severe influenza A/H1N1 pneumonia and acute respiratory distress syndrome. Am J Respir Crit Care Med 2011; 183 (09) 1200-1206
  • 124 Linko R, Pettilä V, Ruokonen E. et al; FINNH1N1-STUDY GROUP. Corticosteroid therapy in intensive care unit patients with PCR-confirmed influenza A(H1N1) infection in Finland. Acta Anaesthesiol Scand 2011; 55 (08) 971-979
  • 125 World Health Organisation. WHO Guidelines for Pharmacological Management of Pandemic Influenza A(H1N1) 2009 and Other Influenza Viruses. 2010 Feb. Accessed June 20, 2021 at: https://www.ncbi.nlm.nih.gov/books/NBK138515/
  • 126 Moreno G, Rodríguez A, Reyes LF. et al; GETGAG Study Group. Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study. Intensive Care Med 2018; 44 (09) 1470-1482
  • 127 Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam JS, Lim WS. Effect of corticosteroid therapy on influenza-related mortality: a systematic review and meta-analysis. J Infect Dis 2015; 212 (02) 183-194
  • 128 Yang JW, Fan LC, Miao XY. et al. Corticosteroids for the treatment of human infection with influenza virus: a systematic review and meta-analysis. Clin Microbiol Infect 2015; 21 (10) 956-963
  • 129 Zhou Y, Fu X, Liu X. et al. Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis. Sci Rep 2020; 10 (01) 3044
  • 130 Lansbury LE, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Shen Lim W. Corticosteroids as adjunctive therapy in the treatment of influenza: an updated cochrane systematic review and meta-analysis. Crit Care Med 2020; 48 (02) e98-e106
  • 131 Okuno D, Kido T, Muramatsu K. et al. Impact of corticosteroid administration within 7 days of the hospitalization for influenza pneumonia with respiratory failure: a propensity score analysis using a nationwide administrative database. J Clin Med 2021; 10 (03) 494
  • 132 Hung IF, To KK, Lee CK. et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis 2011; 52 (04) 447-456
  • 133 Xu Z, Zhou J, Huang Y. et al. Efficacy of convalescent plasma for the treatment of severe influenza. Crit Care 2020; 24 (01) 469
  • 134 Belongia EA, Irving SA, Waring SC. et al. Clinical characteristics and 30-day outcomes for influenza A 2009 (H1N1), 2008-2009 (H1N1), and 2007-2008 (H3N2) infections. JAMA 2010; 304 (10) 1091-1098
  • 135 Lee N, Chan PK, Lui GC. et al. Complications and outcomes of pandemic 2009 Influenza A (H1N1) virus infection in hospitalized adults: how do they differ from those in seasonal influenza?. J Infect Dis 2011; 203 (12) 1739-1747
  • 136 Rochwerg B, Brochard L, Elliott MW. et al. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J 2017; 50 (02) 1602426
  • 137 Esquinas AM, Egbert Pravinkumar S, Scala R. et al; International NIV Network. Noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review. Eur Respir Rev 2014; 23 (134) 427-438
  • 138 Cournoyer A, Grand'Maison S, Lonergan AM. et al. Oxygen therapy and risk of infection for health care workers caring for patients with viral severe acute respiratory infection: a systematic review and meta-analysis. Ann Emerg Med 2021; 77 (01) 19-31
  • 139 Rodríguez A, Ferri C, Martin-Loeches I. et al; 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. Risk factors for noninvasive ventilation failure in critically ill subjects with confirmed influenza infection. Respir Care 2017; 62 (10) 1307-1315
  • 140 Rello J, Pérez M, Roca O. et al; CRIPS investigators. High-flow nasal therapy in adults with severe acute respiratory infection: a cohort study in patients with 2009 influenza A/H1N1v. J Crit Care 2012; 27 (05) 434-439
  • 141 Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342 (18) 1301-1308
  • 142 Simonis FD, Binnekade JM, Braber A. et al. PReVENT—protective ventilation in patients without ARDS at start of ventilation: study protocol for a randomized controlled trial. Trials 2015; 16: 226
  • 143 Martin-Loeches I, Bos LD, Goligher EC. Will all ARDS patients be receiving mechanical ventilation in 2035? Yes. Intensive Care Med 2017; 43 (04) 568-569
  • 144 Briel M, Meade M, Mercat A. et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 2010; 303 (09) 865-873
  • 145 Cavalcanti AB, Suzumura ÉA, Laranjeira LN. et al; Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA 2017; 318 (14) 1335-1345
  • 146 Murias G, Lucangelo U, Blanch L. Patient-ventilator asynchrony. Curr Opin Crit Care 2016; 22 (01) 53-59
  • 147 Blanch L, Villagra A, Sales B. et al. Asynchronies during mechanical ventilation are associated with mortality. Intensive Care Med 2015; 41 (04) 633-641
  • 148 Papazian L, Forel JM, Gacouin A. et al; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010; 363 (12) 1107-1116
  • 149 Moss M, Huang DT. National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. et al. Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med 2019; 380 (21) 1997-2008
  • 150 Guérin C, Beuret P, Constantin JM. et al; 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. A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study. Intensive Care Med 2018; 44 (01) 22-37
  • 151 Guérin C, Reignier J, Richard JC. et al; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368 (23) 2159-2168
  • 152 Xu Y, Deng X, Han Y. et al. A multicenter retrospective review of prone position ventilation (PPV) in treatment of severe Human H7N9 Avian Flu. PLoS One 2015; 10 (08) e0136520
  • 153 Patel BV, Haar S, Handslip R. et al; United Kingdom COVID-ICU National Service Evaluation. Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom. Intensive Care Med 2021; 47 (05) 549-565
  • 154 Boots RJ, Lipman J, Lassig-Smith M. et al. Experience with high frequency oscillation ventilation during the 2009 H1N1 influenza pandemic in Australia and New Zealand. Anaesth Intensive Care 2011; 39 (05) 837-846
  • 155 Ferguson ND, Cook DJ, Guyatt GH. et al; OSCILLATE Trial Investigators, Canadian Critical Care Trials Group. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med 2013; 368 (09) 795-805
  • 156 Young D, Lamb SE, Shah S. et al; OSCAR Study Group. High-frequency oscillation for acute respiratory distress syndrome. N Engl J Med 2013; 368 (09) 806-813
  • 157 Meade MO, Young D, Hanna S. et al. Severity of hypoxemia and effect of high-frequency oscillatory ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 2017; 196 (06) 727-733
  • 158 Abrams D, Combes A, Brodie D. Extracorporeal membrane oxygenation in cardiopulmonary disease in adults. J Am Coll Cardiol 2014; 63 (25 Pt A): 2769-2778
  • 159 Zangrillo A, Biondi-Zoccai G, Landoni G. et al. 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 2013; 17 (01) R30
  • 160 Sukhal S, Sethi J, Ganesh M, Villablanca PA, Malhotra AK, Ramakrishna H. Extracorporeal membrane oxygenation in severe influenza infection with respiratory failure: a systematic review and meta-analysis. Ann Card Anaesth 2017; 20 (01) 14-21