Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Non-influenza respiratory viruses in adult patients admitted with influenza-like illness: a 3-year prospective multicenter study



To describe the burden, and characteristics, of influenza-like illness (ILI) associated with non-influenza respiratory viruses (NIRV).


We performed a prospective, multicenter, observational study of adults admitted with ILI during three influenza seasons (2012–2015). Patients were screened for picornavirus, respiratory syncytial virus (RSV), coronavirus, human metapneumovirus, adenovirus, bocavirus, parainfluenza virus, and influenza, by PCR on nasopharyngeal samples. We excluded patients coinfected with NIRV and influenza.


Among 1421 patients enrolled, influenza virus was detected in 535 (38%), and NIRV in 215 (15%), mostly picornavirus (n = 61), RSV (n = 53), coronavirus 229E (n = 48), and human metapneumovirus (n = 40). In-hospital mortality was 5% (NIRV), 4% (influenza), and 5% (no respiratory virus). As compared to influenza, NIRV were associated with age (median, 73 years vs. 68, P = 0.026), chronic respiratory diseases (53% vs. 45%, P = 0.034), cancer (14% vs. 9%, P = 0.029), and immunosuppressive drugs (21% vs. 14%, P = 0.028), and inversely associated with diabetes (18% vs. 25%, P = 0.038). On multivariable analysis, only chronic respiratory diseases (OR 1.5 [1.1–2.0], P = 0.008), and diabetes (OR 0.5 [0.4–0.8], P = 0.01) were associated with NIRV detection.


NIRV are common in adults admitted with ILI during influenza seasons. Outcomes are similar in patients with NIRV, influenza, or no respiratory virus.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. 1.

    Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet Lond Engl. 2011;377:1264–75. https://doi.org/10.1016/S0140-6736(10)61459-6.

  2. 2.

    Luchsinger V, Ruiz M, Zunino E, Martínez MA, Machado C, Piedra PA, et al. Community-acquired pneumonia in Chile: the clinical relevance in the detection of viruses and atypical bacteria. Thorax. 2013;68:1000–6. https://doi.org/10.1136/thoraxjnl-2013-203551.

  3. 3.

    van den Hoogen BG, de Jong JC, Groen J, Kuiken T, de Groot R, Fouchier RAM, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. 2001;7:719–24. https://doi.org/10.1038/89098.

  4. 4.

    Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B. Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci USA. 2005;102:12891–6. https://doi.org/10.1073/pnas.0504666102.

  5. 5.

    Pavia AT. What is the role of respiratory viruses in community-acquired pneumonia? What is the best therapy for influenza and other viral causes of community-acquired pneumonia? Infect Dis Clin North Am. 2013;27:157–75. https://doi.org/10.1016/j.idc.2012.11.007.

  6. 6.

    Galván JM, Rajas O, Aspa J. Review of non-bacterial infections in respiratory medicine: viral pneumonia. Arch Bronconeumol Engl Ed. 2015;51:590–7. https://doi.org/10.1016/j.arbr.2015.09.015.

  7. 7.

    European Centre for Disease Prevention and Control. Influenza case definitions. 2019. https://ecdc.europa.eu/en/healthtopics/influenza/surveillance/Pages/influenza_case_definitions.aspx. Accessed 9 Jan 2020.

  8. 8.

    Rondy M, Puig-Barbera J, Launay O, Duval X, Castilla J, Guevara M, et al. 2011–12 seasonal influenza vaccines effectiveness against confirmed A(H3N2) influenza hospitalisation: pooled analysis from a European network of hospitals. A pilot study. PLoS One. 2013;8:e59681. https://doi.org/10.1371/journal.pone.0059681.

  9. 9.

    Loubet P, Samih-Lenzi N, Galtier F, Vanhems P, Loulergue P, Duval X, et al. Factors associated with poor outcomes among adults hospitalized for influenza in France: a three-year prospective multicenter study. J Clin Virol. 2016;79:68–73. https://doi.org/10.1016/j.jcv.2016.04.005.

  10. 10.

    Loubet P, Lenzi N, Valette M, Foulongne V, Krivine A, Houhou N, et al. Clinical characteristics and outcome of respiratory syncytial virus infection among adults hospitalized with influenza-like illness in France. Clin Microbiol Infect. 2017;23:253–9. https://doi.org/10.1016/j.cmi.2016.11.014.

  11. 11.

    Bouscambert Duchamp M, Casalegno JS, Gillet Y, Frobert E, Bernard E, Escuret V, et al. Pandemic A(H1N1)2009 influenza virus detection by real time RT-PCR: is viral quantification useful? Clin Microbiol Infect. 2010;16:317–21. https://doi.org/10.1111/j.1469-0691.2010.03169.x.

  12. 12.

    R: The R Project for Statistical Computing. 2019. https://www.r-project.org/.

  13. 13.

    Tanner H, Boxall E, Osman H. Respiratory viral infections during the 2009–2010 winter season in Central England, UK: incidence and patterns of multiple virus co-infections. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2012;31:3001–6. https://doi.org/10.1007/s10096-012-1653-3.

  14. 14.

    Ambrosioni J, Bridevaux P-O, Wagner G, Mamin A, Kaiser L. Epidemiology of viral respiratory infections in a tertiary care centre in the era of molecular diagnosis, Geneva, Switzerland, 2011–2012. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2014;20:O578–584. https://doi.org/10.1111/1469-0691.12525.

  15. 15.

    Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352:1749–59. https://doi.org/10.1056/NEJMoa043951.

  16. 16.

    Zwaans WAR, Mallia P, van Winden MEC, Rohde GGU. The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease—a systematic review. J Clin Virol Off Publ Pan Am Soc Clin Virol 2014;61:181–8. https://doi.org/10.1016/j.jcv.2014.06.025

  17. 17.

    Gunawardana N, Finney L, Johnston SL, Mallia P. Experimental rhinovirus infection in COPD: implications for antiviral therapies. Antiviral Res. 2014;102:95–105. https://doi.org/10.1016/j.antiviral.2013.12.006.

  18. 18.

    Mallia P, Message SD, Gielen V, Contoli M, Gray K, Kebadze T, et al. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am J Respir Crit Care Med. 2011;183:734–42. https://doi.org/10.1164/rccm.201006-0833OC.

  19. 19.

    Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care. 2003;26:510–3. https://doi.org/10.2337/diacare.26.2.510.

  20. 20.

    Pearson-Stuttard J, Blundell S, Harris T, Cook DG, Critchley J. Diabetes and infection: assessing the association with glycaemic control in population-based studies. Lancet Diabetes Endocrinol. 2016;4:148–58. https://doi.org/10.1016/S2213-8587(15)00379-4.

  21. 21.

    Muller LMAJ, Gorter KJ, Hak E, Goudzwaard WL, Schellevis FG, Hoepelman AIM, et al. Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus. Clin Infect Dis Off Publ Infect Dis Soc Am 2005;41:281–8. https://doi.org/10.1086/431587

  22. 22.

    Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-Acquired Pneumonia Requiring Hospitalization among US Adults. N Engl J Med 2015;373:415–27. https://doi.org/10.1056/NEJMoa1500245

Download references


The current work received no funding. However, the study sites received funding from Sanofi Pasteur and Sanofi Pasteur MSD for the FLUVAC study. Vaccine producers had no role in the study design, data analysis, decision to publish or preparation of the manuscript. The FLUVAC Study group. Hôpital Cochin, Paris: P. Loulergue, S. Momcilovic, JP Mira, N. Marin, A. Regent, Kanaan, F. Dumas, B. Doumenc. Hôpital Bichat Claude Bernard, Paris: J.F. Alexandra, H. Becheur, K. Belghalem, J. Bernard, A. Bleitreu, M. Boisseau, R. Bories, O. Brugiere, F. Brunet, C. Burdet, E. Casalino, M. Caseris, Chansiaux, M. Chauchard, P. Chavance, C. Choquet, Cloppet-Fontaine, L. Colosi, B. Couset, B. Crestani, F. Crocket, A. Debit, Delanoe, V. Descamps, P. Dieude, A. Dossier, N. Douron, E. Dupeyrat, N. Emeyrat, Fernet, T. Goulenok, S. Harent, Jouenne, A. Justet, M. Lachatre, A. Leleu, I. Lerat, M. Lilamand, H. Mal, A. Marceau, A-C Metivier, K. Oplelatora, T. Papo, A-L. Pelletier, L. Pereira, P. Pradere, Prommier, P. Ralainnazava, M. Ranaivoision, A. Raynaud-Simon, C. Rioux, K. Sacre, V. Verry, V. Vuong, Y. Yazdapanah. CHU de Montpellier: P. Géraud, V. Driss, V. Maugueret, M. Ray, F. Letois, T. Mura, C. Merle, A. Bourdin, A. Konaté, X. Capdevilla, G. Du Cailar, A. Terminet, H. Blain, M.-S. Leglise, A. Le Quellec, P. Corne, L. Landreau, K. Klouche, A. Bourgeois, M. Sebbane, G. Mourad, H. Leray, M. Maarouf. CHU Dupuytren, Limoges: D. Postil, S. Alcolea, E. Couve Deacon, S. Rogez. Hôpital Edouard Herriot, Lyon: L. Argaud, K. Tazarourte, R. Hernu, M. Cour, M. Simon, T. Baudry, L. Jacquin. CHU Pontchaillou, Rennes: F. Lainé, B. Laviolle, J.-S. Allain, N. Belhomme, V. Thibault, S. Rochas, S. Cochennec, E. Ouamara-Digue, C. Lepape, M. Revest, S. Simon, J. Fouchard, C. Gautier, N. Nouredine, E. Thébault.

Author information

Correspondence to Pierre Tattevin.

Ethics declarations

Conflict of interest

The authors declare no competing interest related to the study. O Launay is an investigator for clinical trials sponsored by Janssen and other companies and received travel support to attend scientific meetings from pharmaceutical companies.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bénézit, F., Loubet, P., Galtier, F. et al. Non-influenza respiratory viruses in adult patients admitted with influenza-like illness: a 3-year prospective multicenter study. Infection (2020). https://doi.org/10.1007/s15010-019-01388-1

Download citation


  • Influenza-like illness
  • Influenza
  • Picornavirus
  • Respiratory syncytial virus
  • Coronavirus
  • Human metapneumovirus