EBM Review: Clinical utility of PCR for common viruses in acute respiratory illness.

Rhedin S, Lindstrand A, Rotzén-Östlund M, et al. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics. 2014 Mar;133(3):e538-45.

Full-text for Children’s and Emory users.

BACKGROUND: Acute respiratory illness (ARI) accounts for a large proportion of all visits to pediatric health facilities. Quantitative real-time polymerase chain reaction (qPCR) analyses allow sensitive detection of viral nucleic acids, but it is not clear to what extent specific viruses contribute to disease because many viruses have been detected in asymptomatic children. Better understanding of how to interpret viral findings is important to reduce unnecessary use of antibiotics.

OBJECTIVE: To compare viral qPCR findings from children with ARI versus asymptomatic control subjects.

METHODS: Nasopharyngeal aspirates were collected from children aged ≤5 years with ARI and from individually matched, asymptomatic, population-based control subjects during a noninfluenza season. Samples were analyzed by using qPCR for 16 viruses.

RESULTS: Respiratory viruses were detected in 72.3% of the case patients (n = 151) and 35.4% of the control subjects (n = 74) (P = .001). Rhinovirus was the most common finding in both case patients and control subjects (47.9% and 21.5%, respectively), with a population-attributable proportion of 0.39 (95% confidence interval: 0.01 to 0.62). Metapneumovirus, parainfluenza viruses, and respiratory syncytial virus were highly overrepresented in case patients. Bocavirus was associated with ARI even after adjustment for coinfections with other viruses and was associated with severe disease. Enterovirus and coronavirus were equally common in case patients and control subjects.

CONCLUSIONS: qPCR detection of respiratory syncytial virus, metapneumovirus, or parainfluenza viruses in children with ARI is likely to be causative of disease; detection of several other respiratory viruses must be interpreted with caution due to high detection rates in asymptomatic children.

Reviewed by: 

Liesl Windsor, MD Liesl Windsor, MD

Neil Cella, MD Neil Cella, MD

A clinical scenario:

  • 18 month old male ex 27 weeks with h/oCLD, developmental delay, and G-tube presenting with:
    • 3 days fever
    • Very worried caregivers – last respiratory illness ended up as intubation
    • Runny nose, cough and emesis
    • Increased oxygen requirement from ¼ LPM to 1 LPM
    • Less active and more fussy, attends medically fragile daycare
    • Exam – TMs clear, nasal congestion, normal cardiac exam, mild tachypnea, no retractions, no wheeze, crackles bilaterally, no focally decreased breath sounds
    • CXR – RUL atelectasis versus focal pneumonia
    • Admitted for hypoxia –  ED sent VRP and it has come back positive for Adenovirus. Does this help in antibiotic decision making on admission?


  • Matched Case-Control Study
    • Cases – children aged less than or equal to 5 years with one or more of the following:
      • Coryza, sore throat, earache, cough, sputum production, or dyspnea
      • Only included in study once; enrolled from September 2011 to January 2012
    • Matched controls
      • According to calendar time(+ or – 14 days) and age(+ or – 6 months)
      • Enrolled from local swedish vaccination program
      • Excluded if reports of respiratory disease in prior 7 days
      • If no match found, controls expanded to +/- 30 days and +/- 12 months

What do we think of this study design?

  • These authors have used this phrase “case-control” study, but it is more of a cohort
  • Advantages – practical and affordable
  • Disadvantages – retrospective nature, difficult to match control group

Strengths of study:

  • Observational design
  • Attempted to match
  • Sample size?
  • Impact of journal
  • Clinically relevant

Weaknesses of study:

  • Observational Design – unable to choose the patients that will be affected
  • Compared two different groups
    • Controls were younger and more frequently female; less attended day care; more breast fed; less had asthma; less were being treated with antibiotics; less were children of higher educated parents
  • No follow up – early detection in controls? Asymptomatic carriage? No microbiological investigation for bacteria
  • Qualitative versus quantitative PCR

Return to case and further questions:

  • In this study, adenovirus detection in cases did not differ significantly from controls
  • We can only apply results to diagnosis and all management questions are not related to this study
  • Still, would Adenovirus positivity stop us from treating him for bacterial super-infection?
  • If he was Parainfluenza+ or co-infected, would this stop us from treating him for super-infected pneumonia?
  • Is there value in a diagnosis beyond management? Very worried parents? Epidemiology at an academic center?
  • Will cost come down with time?