Journal of Clinical Virology 60 (2014) 133–140 Contents lists available at ScienceDirect Journal of Clinical Virology jou rn al hom epage: www.elsevier.com/locate/jcv Human metapneumovirus viral load is an important risk factor for disease severity in young children Jean-Franc ¸ ois Roussy a , Julie Carbonneau a , Manale Ouakki b , Jesse Papenburg c , Marie-Ève Hamelin a , Gaston De Serres b , Guy Boivin a,∗ a Research Center in Infectious Diseases of the CHU of Québec and Laval University, Quebec City, QC, Canada b Institut National de Santé Publique du Québec, Quebec City, QC, Canada c McGill University Health Centre, Montréal, QC, Canada a r t i c l e i n f o Article history: Received 29 January 2014 Received in revised form 28 February 2014 Accepted 3 March 2014 Keywords: Human metapneumovirus Viral load Hospitalization Severity Pediatric a b s t r a c t Background: The role of viral load in human metapneumovirus (HMPV) disease severity has not yet been clearly determined. Objective: We evaluated the importance of viral load along with other factors in HMPV disease severity among children aged <3 years old. Study design: HMPV-positive cases were selected from a cohort of outpatients and hospitalized children with lower respiratory tract infections. HMPV groups (A or B) and viral loads were determined in their nasopharyngeal aspirates. Disease severity was defined by assessing risk for hospitalization and by using two validated clinical severity scores. Results: Of the 118 HMPV cases detected over 4 years for which viral load could be determined, 60 belonged to genotype A and 58 to genotype B. Baseline characteristics were similar in HMPV-A and HMPV-B mono-infected patients. In multivariate analysis, HMPV hospitalization was associated with viral load ≥1000 copies/10 4 cells (OR, 3.2; 95%CI, 1.4–7.4), age <6 months (OR, 3.1; 95%CI, 1.2–8.6) and presence of ≥3 children in the household (OR, 2.7; 95%CI, 1.04–6.9). A high HMPV viral load was also associated with pulmonary rales (p = .03), use of bronchodilators (p = .02) and inhaled corticosteroids (p = .01). Conclusion: HMPV viral load is associated with disease severity in young children along with young age and household crowding. © 2014 Elsevier B.V. All rights reserved. 1. Background Respiratory tract infections (RTIs) are the second leading cause of death in children under the age of 5 years worldwide [1]. The majority of RTI are thought to be caused by viruses, among which human metapneumovirus (HMPV) figures prominently [2,3]. Indeed, HMPV accounts for 5–15% of all respiratory viral infections Abbreviations: RTI, respiratory tract infection; HMPV, human metapeumovirus; HMPV-Ac, human metapneumovirus group A infected cohort; HMPV-Bc, human metapneumovirus group B infected cohort; RSV, respiratory syncytial virus; PCR, polymerase chain reaction; CSS, clinical severity score; NPA, nasopharyngeal aspi- rate; LNA, locked nucleic acid probes; RR, relative risk; OR, adjusted odd ratio; CI, confidence interval; VL, viral load; LBW, low birth weight. ∗ Corresponding author at: CHUL, Room RC-709, 2705 blvd Laurier, Sainte-Foy, QC, Canada G1V 4G2. Tel.: +1 418 654 2705; fax: +1 418 654 2715. E-mail address: Guy.Boivin@crchul.ulaval.ca (G. Boivin). requiring hospitalization in children compared to 40–50% for respiratory syncytial virus (RSV) [4]. The clinical presentations of HMPV and RSV infections are indistinguishable and mainly include bronchiolitis and pneumonia in infants [4]. Based on phylogenetic analysis of the F and G genes, two main genetic groups (A and B) and 5 lineages of HMPV circulate in humans [3,5]. Whether these HMPV lineages are associated with different clinical outcomes remains unresolved [6]. In that regard, sev- eral groups found no evidence for differential severity between groups [7,8], whereas others suggested more severe clinical dis- ease associated with HMPV-A [9] or HMPV-B [10] strains. Our group previously reported that, in children aged <3 years, HMPV-B was an independent risk factor for severe disease among hospitalized patients, along with female sex and prematurity [11]. However, the influence of HMPV viral load (VL), a factor possibly involved in disease severity [12,13], was not investigated in those previous studies. http://dx.doi.org/10.1016/j.jcv.2014.03.001 1386-6532/© 2014 Elsevier B.V. All rights reserved.