Risk of mortality associated with respiratory syncytial virus and influenza infection in adults

Yong Shik Kwon, Sun Hyo Park, Mi-Ae Kim, Hyun Jung Kim, Jae Seok Park, Mi Young Lee, Choong Won Lee, Sonila Dauti, Won-Il Choi, Yong Shik Kwon, Sun Hyo Park, Mi-Ae Kim, Hyun Jung Kim, Jae Seok Park, Mi Young Lee, Choong Won Lee, Sonila Dauti, Won-Il Choi

Abstract

Background: Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection.

Methods: A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013-2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death.

Results: Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17-4.58). Oseltamivir had no significant effect on mortality in patients with influenza.

Conclusions: RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.

Keywords: Influenza, human; Mortality; Respiratory syncytial viruses.

Conflict of interest statement

Ethics approval and consent to participate

The current study was approved by the institutional review board at Dongsan Hospital, Keimyung University School of Medicine. The need for written informed consent was waived. This study was conducted in compliance with the Declaration of Helsinki.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of patients suffering from respiratory virus infection
Fig. 2
Fig. 2
Time of hospital admission of 87 adult patients with virologically confirmed respiratory syncytial virus (RSV) infection, and 312 adult patients with influenza infection, Daegu, Korea, 2013–2015. RSV seasonal peaks occurred during January in 2013, December in 2014, and January in 2015; the percentage test positivity rates during these periods were 11.4% and 40.8% for RSV and influenza, respectively among virus identified patients. Abbreviation: RSV, respiratory syncytial virus
Fig. 3
Fig. 3
Kaplan-Meier survival curves of 399 adults hospitalized with respiratory syncytial virus (RSV, red line) and influenza infection (blue line). Patients with RSV infection were shown to have lower survival rates. Between RSV and influenza infected patients, the crude 20-day all-cause mortality rate among RSV and influenza infected patients was 18.4% and 6.7%, respectively
Fig. 4
Fig. 4
Kaplan-Meier survival curves of 312 adults hospitalized for influenza virus infection, who did not undergo oseltamivir therapy (red line, n = 65) and who did undergo oseltamivir therapy (blue line, n = 247). Twenty-day all-cause mortality rates among influenza patients treated with and without oseltamivir were 6.4% and 7.6%, respectively (P = 0.72)

References

    1. Boyce TG, Mellen BG, Mitchel EF, Jr, Wright PF, Griffin MR. Rates of hospitalization for respiratory syncytial virus infection among children in medicaid. J Pediatr. 2000;137(6):865–870. doi: 10.1067/mpd.2000.110531.
    1. Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatr. 2003;143(5 Suppl):S127–S132. doi: 10.1067/S0022-3476(03)00510-9.
    1. Falsey AR, Walsh EE, Betts RF. Serologic evidence of respiratory syncytial virus infection in nursing home patients. J Infect Dis. 1990;162(2):568–569. doi: 10.1093/infdis/162.2.568.
    1. Falsey AR, Treanor JJ, Betts RF, Walsh EE. Viral respiratory infections in the institutionalized elderly: clinical and epidemiologic findings. J Am Geriatr Soc. 1992;40(2):115–119. doi: 10.1111/j.1532-5415.1992.tb01929.x.
    1. Garvie DG, Gray J. Outbreak of respiratory syncytial virus infection in the elderly. Br Med J. 1980;281(6250):1253–1254. doi: 10.1136/bmj.281.6250.1253-a.
    1. Hornsleth A, Siggaard-Andersen J, Hjort L. Epidemiology of herpesvirus and respiratory virus infections. Part 1. Serologic findings. Geriatrics. 1975;30(8):61–68.
    1. Sica S, Leone G, Marra R, Falappa PG, Spanu T, Pagliari G, Mango G, Bizzi B. Respiratory syncytial virus infection in bone marrow transplantation: a case report (syncytial virus infection) Haematologica. 1990;75(2):184–186.
    1. Sinnott JT, Cullison JP, Sweeney MS, Hammond M, Holt DA. Respiratory syncytial virus pneumonia in a cardiac transplant recipient. J Infect Dis. 1988;158(3):650–651. doi: 10.1093/infdis/158.3.650.
    1. Wendt CH. Community respiratory viruses: organ transplant recipients. Am J Med. 1997;102(3A):31–36. doi: 10.1016/S0002-9343(97)80008-3.
    1. Whimbey E, Englund JA, Couch RB. Community respiratory virus infections in immunocompromised patients with cancer. Am J Med. 1997;102(3A):10–18. doi: 10.1016/S0002-9343(97)80004-6.
    1. 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(17):1749–1759. doi: 10.1056/NEJMoa043951.
    1. Lee N, Lui GC, Wong KT, Li TC, Tse EC, Chan JY, Yu J, Wong SS, Choi KW, Wong RY, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069–1077. doi: 10.1093/cid/cit471.
    1. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373(5):415–427. doi: 10.1056/NEJMoa1500245.
    1. Miggins M, Hasan A, Hohmann S, Southwick F, Casella G, Schain D, Liu H, Bihorac A, Moldawer L, Efron P, et al. The potential influence of common viral infections diagnosed during hospitalization among critically ill patients in the United States. PLoS One. 2011;6(4):e18890. doi: 10.1371/journal.pone.0018890.
    1. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359(22):2355–2365. doi: 10.1056/NEJMra0800353.
    1. van Asten L, van den Wijngaard C, van Pelt W, van de Kassteele J, Meijer A, van der Hoek W, Kretzschmar M, Koopmans M. Mortality attributable to 9 common infections: significant effect of influenza a, respiratory syncytial virus, influenza B, norovirus, and parainfluenza in elderly persons. J Infect Dis. 2012;206(5):628–639. doi: 10.1093/infdis/jis415.
    1. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289(2):179–186. doi: 10.1001/jama.289.2.179.
    1. Matias G, Taylor R, Haguinet F, Schuck-Paim C, Lustig R, Shinde V. Estimates of mortality attributable to influenza and RSV in the United States during 1997-2009 by influenza type or subtype, age, cause of death, and risk status. Influenza Other Respir Viruses. 2014;8(5):507–515. doi: 10.1111/irv.12258.
    1. Matias G, Taylor R, Haguinet F, Schuck-Paim C, Lustig R, Shinde V. Estimates of hospitalization attributable to influenza and RSV in the US during 1997-2009, by age and risk status. BMC Public Health. 2017;17(1):271. doi: 10.1186/s12889-017-4177-z.
    1. Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP, Cheung A, Hovhannisyan G, Ivanova L, Flottorp SA, et al. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med. 2012;156(7):512–524. doi: 10.7326/0003-4819-156-7-201204030-00411.
    1. Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014;348:g2545. doi: 10.1136/bmj.g2545.
    1. McGeer A, Green KA, Plevneshi A, Shigayeva A, Siddiqi N, Raboud J, Low DE. Toronto invasive bacterial diseases N: antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis. 2007;45(12):1568–1575. doi: 10.1086/523584.
    1. Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TS, Al Mamun A, Anovadiya AP, Azziz-Baumgartner E, Baez C, Bassetti M, et al. 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(5):395–404. doi: 10.1016/S2213-2600(14)70041-4.
    1. Wang CB, Chiu ML, Lin PC, Liang WM, Chen CY, Chang YJ, Wu TN, Wang JH, Sung FC. Prompt Oseltamivir therapy reduces medical care and mortality for patients with influenza infection: an Asian population cohort study. Medicine. 2015;94(27):e1070. doi: 10.1097/MD.0000000000001070.
    1. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015;385(9979):1729–1737. doi: 10.1016/S0140-6736(14)62449-1.
    1. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336(4):243–250. doi: 10.1056/NEJM199701233360402.
    1. Raghunathan TE, Lepkowski JM, Van Hoewyk J, Solenberger P. A multivariate technique for multiply imputing missing values using a sequence of regression models. Surv Methodol. 2001;27:85–95.
    1. Field A. Discovering statistics using IBM SPSS statistics. 4. Los Angeles: SAGE; 2013.
    1. Kleinbaum DG, Klein M. Survival analysis: a self-learning text. New York: Springer; 2012.
    1. Branche AR, Falsey AR. Respiratory syncytial virus infection in older adults: an under-recognized problem. Drugs Aging. 2015;32(4):261–269. doi: 10.1007/s40266-015-0258-9.
    1. Volling C, Hassan K, Mazzulli T, Green K, Al-Den A, Hunter P, Mangat R, Ng J, McGeer A. Respiratory syncytial virus infection-associated hospitalization in adults: a retrospective cohort study. BMC Infect Dis. 2014;14:665. doi: 10.1186/s12879-014-0665-2.
    1. Lee N, Chan MC, Lui GC, Li R, Wong RY, Yung IM, Cheung CS, Chan EC, Hui DS, Chan PK. High viral load and respiratory failure in adults hospitalized for respiratory Syncytial virus infections. J Infect Dis. 2015;212(8):1237–1240. doi: 10.1093/infdis/jiv248.
    1. Ong DS, Faber TE, Klein Klouwenberg PM, Cremer OL, Christiaan Boerma E, Sietses M, van Loon AM, Bonten MJ, Bont LJ. Respiratory syncytial virus in critically ill adult patients with community-acquired respiratory failure: a prospective observational study. Clin Microbiol Infect. 2014;20(8):O505–O507. doi: 10.1111/1469-0691.12503.
    1. Fleming DM, Pannell RS, Cross KW. Mortality in children from influenza and respiratory syncytial virus. J Epidemiol Community Health. 2005;59(7):586–590. doi: 10.1136/jech.2004.026450.
    1. Shay DK, Holman RC, Roosevelt GE, Clarke MJ, Anderson LJ. Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979-1997. J Infect Dis. 2001;183(1):16–22. doi: 10.1086/317655.
    1. Hart RJ. An outbreak of respiratory syncytial virus infection in an old people's home. J Infect. 1984;8(3):259–261. doi: 10.1016/S0163-4453(84)94075-1.
    1. Fleming DM, Cross KW. Respiratory syncytial virus or influenza? Lancet. 1993;342(8886-8887):1507–1510. doi: 10.1016/S0140-6736(05)80082-0.
    1. Jansen AG, Sanders EA, Hoes AW, van Loon AM, Hak E. Influenza- and respiratory syncytial virus-associated mortality and hospitalisations. Eur Respir J. 2007;30(6):1158–1166. doi: 10.1183/09031936.00034407.
    1. Falsey AR, Cunningham CK, Barker WH, Kouides RW, Yuen JB, Menegus M, Weiner LB, Bonville CA, Betts RF. Respiratory syncytial virus and influenza a infections in the hospitalized elderly. J Infect Dis. 1995;172(2):389–394. doi: 10.1093/infdis/172.2.389.
    1. Nicholson KG. Impact of influenza and respiratory syncytial virus on mortality in England and Wales from January 1975 to December 1990. Epidemiol Infect. 1996;116(1):51–63. doi: 10.1017/S0950268800058957.
    1. Respiratory syncytial virus (RSV) surveillance. [].
    1. Boivin G, Cote S, Dery P, De Serres G, Bergeron MG. Multiplex real-time PCR assay for detection of influenza and human respiratory syncytial viruses. J Clin Microbiol. 2004;42(1):45–51. doi: 10.1128/JCM.42.1.45-51.2004.
    1. Frisbie B, Tang YW, Griffin M, Poehling K, Wright PF, Holland K, Edwards KM. Surveillance of childhood influenza virus infection: what is the best diagnostic method to use for archival samples? J Clin Microbiol. 2004;42(3):1181–1184. doi: 10.1128/JCM.42.3.1181-1184.2004.
    1. Smith AB, Mock V, Melear R, Colarusso P, Willis DE. Rapid detection of influenza a and B viruses in clinical specimens by light cycler real time RT-PCR. J Clin Virol. 2003;28(1):51–58. doi: 10.1016/S1386-6532(02)00238-X.
    1. Gueudin M, Vabret A, Petitjean J, Gouarin S, Brouard J, Freymuth F. Quantitation of respiratory syncytial virus RNA in nasal aspirates of children by real-time RT-PCR assay. J Virol Methods. 2003;109(1):39–45. doi: 10.1016/S0166-0934(03)00042-9.
    1. Glezen WP, Greenberg SB, Atmar RL, Piedra PA, Couch RB. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA. 2000;283(4):499–505. doi: 10.1001/jama.283.4.499.
    1. Dowell SF, Anderson LJ, Gary HE, Jr, Erdman DD, Plouffe JF, File TM, Jr, Marston BJ, Breiman RF. Respiratory syncytial virus is an important cause of community-acquired lower respiratory infection among hospitalized adults. J Infect Dis. 1996;174(3):456–462. doi: 10.1093/infdis/174.3.456.
    1. Sorvillo FJ, Huie SF, Strassburg MA, Butsumyo A, Shandera WX, Fannin SL. An outbreak of respiratory syncytial virus pneumonia in a nursing home for the elderly. J Inf Secur. 1984;9(3):252–256.
    1. Walsh EE, Peterson DR, Falsey AR. Is clinical recognition of respiratory syncytial virus infection in hospitalized elderly and high-risk adults possible? J Infect Dis. 2007;195(7):1046–1051. doi: 10.1086/511986.
    1. DeVincenzo JP, Whitley RJ, Mackman RL, Scaglioni-Weinlich C, Harrison L, Farrell E, McBride S, Lambkin-Williams R, Jordan R, Xin Y, et al. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med. 2014;371(8):711–722. doi: 10.1056/NEJMoa1401184.
    1. Mejias A, Ramilo O. New options in the treatment of respiratory syncytial virus disease. J Infect. 2015;71(Suppl 1):S80–S87. doi: 10.1016/j.jinf.2015.04.025.

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