Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children

Abstract

Background: Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear.

Objectives: To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses.

Patients/methods: Eight hundred and ninety-three residual nasal wash samples from children treated for respiratory illness at Children's Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts.

Results: Coinfections were identified in 103 (18%) of 566 virus-positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV-1, multiple virus illnesses had a significantly lower viral load (log(10) copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu-A, PIV-3, and hMPV viral loads were consistently high whether or not another virus was detected.

Conclusions: Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections.

Figure 1

Percent of illnesses with multiple virus detections, by respiratory virus. RSV, respiratory syncytial virus; Flu A, influenza A; AdV, adenovirus; hMPV, human metapneumovirus; CoV, coronavirus; PIV1, parainfluenza type 1; PIV3, parainfluenza type 3.

Figure 2

Distribution of respiratory virus viral loads, by single and multiple detection. Log viral load is shown separately for viruses detected in a single virus illness and those detected in a multiple virus illness. The number of positive detections for which quantitation was available for each virus is listed above each box. RSV, respiratory syncytial virus; Flu A, influenza A; AdV, adenovirus; hMPV, human metapneumovirus; CoV, coronavirus; PIV1, parainfluenza type 1; PIV3, parainfluenza type 3. ^aCoV quantitation available for subtypes 229E (n = 7) and OC43 (n = 15) only.