Download PDF
J Pediatr Intensive Care 2022; 11(01): 013-018
DOI: 10.1055/s-0040-1718868
Original Article

Adenoviral Respiratory Infection-Associated Mortality in Children: A Retrospective Case Series

Michael C. Spaeder 
1   Division of Pediatric Critical Care, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States
,
Claire Stewart
2   Division of Critical Care Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States
,
Matthew P. Sharron
3   Division of Critical Care Medicine, Children's National Hospital, Washington, District of Columbia, United States
,
Julia R. Noether 
4   Division of Pediatric Critical Care, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, United States
,
Natalia Martinez-Schlurman 
5   Division of Pediatric Critical Care, University of Florida School of Medicine, Gainesville, Florida, United States
,
Robert P. Kavanagh
6   Division of Pediatric Critical Care, Pennsylvania State University School of Medicine, Hershey, Pennsylvania, United States
,
Jessica K. Signoff 
7   Division of Pediatric Critical Care, University of California at Davis School of Medicine, Sacramento, California, United States
,
Michael C. McCrory
8   Pediatric Critical Care, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
,
Daniel B. Eidman 
9   Pediatric Critical Care, Yale University School of Medicine, New Haven, Connecticut, United States
,
Anjali V. Subbaswamy
10   Division of Pediatric Critical Care, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States
,
Paul L. Shea
11   Division of Pediatric Critical Care, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States
,
Ilana Harwayne-Gidansky
12   Division of Pediatric Critical Care, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, United States
,
Emily K. Ninmer
1   Division of Pediatric Critical Care, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States
,
Mary Lynn Sheram
13   Department of Pediatrics, Medical College of Georgia at Augusta University, Augusta, Georgia, United States
,
Christopher M. Watson
13   Department of Pediatrics, Medical College of Georgia at Augusta University, Augusta, Georgia, United States
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Viral respiratory infections are a leading cause of illness and hospitalization in young children worldwide. Case fatality rates in pediatric patients with adenoviral lower respiratory tract infection requiring intensive care unit (ICU) admission have been reported between 7 and 22%. We investigated the demographics and clinical characteristics in pediatric mortalities associated with adenoviral respiratory infection at 12 academic children's hospitals in the United States. There were 107 mortality cases included in our study, 73% of which had a chronic medical condition. The most common chronic medical condition was immunocompromised state in 37 cases (35%). The incidences of pediatric acute respiratory distress syndrome (78%) and multiple organ dysfunction syndrome (94%) were profound. Immunocompetent cases were more likely to receive mechanical ventilation within the first hour of ICU admission (60 vs. 14%, p < 0.001) and extracorporeal membrane oxygenation (27 vs. 5%, p = 0.009), and less likely to receive continuous renal replacement therapy (20 vs. 49%, p = 0.002) or have renal dysfunction (54 vs. 78%, p = 0.014) as compared with immunocompromised cases. Immunocompromised cases were more likely to have bacteremia (57 vs. 16%, p < 0.001) and adenoviremia (51 vs. 17%, p < 0.001) and be treated with antiviral medications (81 vs. 26%, p < 0.001). We observed a high burden of nonrespiratory organ system dysfunction in a cohort of pediatric case fatalities with adenoviral respiratory infection. The majority of cases had a chronic medical condition associated with an increased risk of complications from viral respiratory illness, most notably immunocompromised state. Important treatment differences were noted between immunocompromised and immunocompetent cases.

Keywords

respiratory tract infections - adenovirus - intensive care - children - pediatric


Publication History

Received: 01 August 2020

Accepted: 19 September 2020

Article published online:
26 October 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Troeger C, Forouzanfar M, Rao PC. et al; GBD 2015 LRI Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis 2017; 17 (11) 1133-1161
    CrossrefPubMedGoogle Scholar
  • 2 Pavia AT. Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis. Clin Infect Dis 2011; 52 (Suppl. 04) S284-S289
    CrossrefPubMedGoogle Scholar
  • 3 Murtagh P, Giubergia V, Viale D, Bauer G, Pena HG. Lower respiratory infections by adenovirus in children. Clinical features and risk factors for bronchiolitis obliterans and mortality. Pediatr Pulmonol 2009; 44 (05) 450-456
    CrossrefPubMedGoogle Scholar
  • 4 Echavarría M. Adenoviruses in immunocompromised hosts. Clin Microbiol Rev 2008; 21 (04) 704-715
    CrossrefPubMedGoogle Scholar
  • 5 Spaeder MC. Severe adenoviral respiratory infection in children. Intensive Care Med 2013; 39 (06) 1157-1158
    CrossrefPubMedGoogle Scholar
  • 6 Lai CY, Lee CJ, Lu CY. et al; Taiwan Pediatric Infectious Disease Alliance. Adenovirus serotype 3 and 7 infection with acute respiratory failure in children in Taiwan, 2010-2011. PLoS One 2013; 8 (01) e53614
    CrossrefPubMedGoogle Scholar
  • 7 Tylka JC, McCrory MC, Gertz SJ, Custer JW, Spaeder MC. Immunocompromised children with severe adenoviral respiratory infection. Crit Care Res Pract 2016; 2016: 9458230
    PubMedGoogle Scholar
  • 8 Spaeder MC, Fackler JC. Hospital-acquired viral infection increases mortality in children with severe viral respiratory infection. Pediatr Crit Care Med 2011; 12 (06) e317-e321
    CrossrefPubMedGoogle Scholar
  • 9 Hong JY, Lee HJ, Piedra PA. et al. Lower respiratory tract infections due to adenovirus in hospitalized Korean children: epidemiology, clinical features, and prognosis. Clin Infect Dis 2001; 32 (10) 1423-1429
    CrossrefPubMedGoogle Scholar
  • 10 Lynch III JP, Fishbein M, Echavarria M. Adenovirus. Semin Respir Crit Care Med 2011; 32 (04) 494-511
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Committee on Infectious Diseases 2019–2020. Pediatrics 2019; 144 (04) e20192478
    CrossrefPubMedGoogle Scholar
  • 12 Khemani RG, Smith LS, Zimmerman JJ, Erickson S. Pediatric Acute Lung Injury Consensus Conference Group. Pediatric acute respiratory distress syndrome: definition, incidence, and epidemiology: proceedings from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 2015; 16 (05, Suppl 1): S23-S40
    CrossrefPubMedGoogle Scholar
  • 13 Goldstein B, Giroir B, Randolph A. International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6 (01) 2-8
    CrossrefPubMedGoogle Scholar
  • 14 Straney L, Clements A, Parslow RC. et al; ANZICS Paediatric Study Group and the Paediatric Intensive Care Audit Network. Paediatric index of mortality 3: an updated model for predicting mortality in pediatric intensive care. Pediatr Crit Care Med 2013; 14 (07) 673-681
    CrossrefPubMedGoogle Scholar
  • 15 Chen J, Hu P, Zhou T. et al. Epidemiology and clinical characteristics of acute respiratory tract infections among hospitalized infants and young children in Chengdu, West China, 2009-2014. BMC Pediatr 2018; 18 (01) 216
    CrossrefPubMedGoogle Scholar
  • 16 Moynihan KM, McGarvey T, Barlow A. et al. Testing for common respiratory viruses in children admitted to pediatric intensive care: epidemiology and outcomes. Pediatr Crit Care Med 2020; 21 (06) e333-e341
    CrossrefPubMedGoogle Scholar
  • 17 Welliver Sr RC, Checchia PA, Bauman JH, Fernandes AW, Mahadevia PJ, Hall CB. Fatality rates in published reports of RSV hospitalizations among high-risk and otherwise healthy children. Curr Med Res Opin 2010; 26 (09) 2175-2181
    CrossrefPubMedGoogle Scholar
  • 18 Coffin SE, Zaoutis TE, Rosenquist AB. et al. Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza. Pediatrics 2007; 119 (04) 740-748
    CrossrefPubMedGoogle Scholar
  • 19 Streng A, Grote V, Liese JG. Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008. BMC Infect Dis 2011; 11: 233
    CrossrefPubMedGoogle Scholar
  • 20 Spaeder MC, Custer JW, Miles AH. et al. A multicenter outcomes analysis of children with severe rhino/enteroviral respiratory infection. Pediatr Crit Care Med 2015; 16 (02) 119-123
    CrossrefPubMedGoogle Scholar
  • 21 Randolph AG, Vaughn F, Sullivan R. Pediatric Acute Lung Injury and Sepsis Investigator's Network and the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. et al. Critically ill children during the 2009-2010 influenza pandemic in the United States. Pediatrics 2011; 128 (06) e1450-e1458
    CrossrefPubMedGoogle Scholar
  • 22 Spaeder MC, Custer JW, Bembea MM, Aganga DO, Song X, Scafidi S. A multicenter outcomes analysis of children with severe viral respiratory infection due to human metapneumovirus. Pediatr Crit Care Med 2013; 14 (03) 268-272
    CrossrefPubMedGoogle Scholar
  • 23 Lion T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin Microbiol Rev 2014; 27 (03) 441-462
    CrossrefPubMedGoogle Scholar
  • 24 Mistchenko AS, Diez RA, Mariani AL. et al. Cytokines in adenoviral disease in children: association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome. J Pediatr 1994; 124 (5 Pt 1): 714-720
    CrossrefPubMedGoogle Scholar
  • 25 Wong HR. Genetics and genomics in pediatric septic shock. Crit Care Med 2012; 40 (05) 1618-1626
    CrossrefPubMedGoogle Scholar
  • 26 Dailey Garnes NJM, Ragoonanan D, Aboulhosn A. Adenovirus infection and disease in recipients of hematopoietic cell transplantation. Curr Opin Infect Dis 2019; 32 (06) 591-600
    CrossrefPubMedGoogle Scholar
  • 27 Ramanathan K, Tan CS, Rycus P, MacLaren G. Extracorporeal membrane oxygenation for severe adenoviral pneumonia in neonatal, pediatric, and adult patients. Pediatr Crit Care Med 2019; 20 (11) 1078-1084
    CrossrefPubMedGoogle Scholar