Quantification of Human Metapneumovirus Load and Disease Severity among Hospitalized Children with Pneumonia Enrolled in the CDC Etiology of Pneumonia in the Community (EPIC) Study

Background: Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is a significant cause of acute respiratory infection in infants and children. We investigated the association between hMPV load and disease severity in hospitalized children with radiographic evidence of pneumonia enrolled in the CDC EPIC study.

Methods: We quantified the viral load of hMPV in naso-/oro-pharyngeal swab specimens obtained from children <18 years old with pneumonia and healthy controls. We screened for hMPV and host RNase P with real-time reverse-transcription PCR and established viral load using standard curves comprised of quantified RNA transcripts. We constructed regression models to assess the association between hMPV load and disease severity indicators.

Results: We tested 675 pneumonia cases and 132 healthy controls enrolled during 01/2010-02/2012. hMPV was detected in 94 (13.9%) of pneumonia cases and 2 (1.5%) of controls (P<0.001). hMPV load among pneumonia cases was 2.3 logs higher than the control group when adjusted for the RNase P internal control (median 6.4 vs 4.1 log copies; P=0.005). Among pneumonia cases, viral load was similar among patients with hMPV detected as the sole pathogen compared with those with >1 virus detected (P=0.8). Viral loads were similar among children <5 years and those 5-17 years of age (median 6.3 vs 6.3 log copies; P=0.2). Additionally, hMPV load was not significantly associated with prolonged length of stay, intensive care unit admission, or requirement for mechanical ventilation but was inversely associated with elevated C-reactive protein (CRP; P=0.008) and elevated white blood cell count at presentation (WBC; P<0.001).

Conclusion: hMPV was more frequently detected among children with pneumonia when compared with healthy controls, supporting the role of hMPV in pneumonia. While hMPV loads were higher among pneumonia patients when compared with controls, rare detection of hMPV among controls limits the precision of this comparison. Surprisingly, lower viral load was associated with high CRP and WBC on admission. Ongoing investigations to identify bacterial co-infection may help explain this.