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Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia.


AUTHORS

Zhang Y , Sakthivel SK , Bramley A , Jain S , Haynes A , Chappell JD , Hymas W , Lenny N , Patel A , Qi C , Ampofo K , Arnold SR , Self WH , Williams DJ , Hillyard D , Anderson EJ , Grijalva CG , Zhu Y , Wunderink RG , Edwards KM , Pavia AT , McCullers JA , Erdman DD , . Journal of clinical microbiology. 2016 10 19; ().
  • NIHMSID: 7505564

ABSTRACT

Both molecular and serological assays have been used previously to determine the etiology of community-acquired pneumonia (CAP). However, the correlation of these methods and added diagnostic value of serology has not been fully evaluated. Using data from patients enrolled in the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, we compared real-time RT-PCR and serology for diagnosis of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza viruses 1-3 (PIV) and adenovirus (AdV) infections. Of 5126 patients enrolled, RT-PCR and serology test results were available for 2023, including 1087 children <18 years of age and 936 adults. For RSV, 287 (14.2%) patients were positive by RT-PCR and 234 (11.6%) were positive by serology; HMPV, 172 (8.5%) tested positive by RT-PCR and 147 (7.3%) by serology; PIVs, 94 (4.6%) tested positive by RT-PCR and 92 (4.6%) by serology; and AdV, 111 (5.5%) positive by RT-PCR and 62 (3.1%) by serology. RT-PCR provided the most positive detections overall, but serology increased diagnostic yield for RSV (by 11.8%), HMPV (by 25.0%), AdV (by 32.4%), and PIV (by 48.9%). Method concordance estimated by Cohen's kappa (κ) coefficient ranged from good (RSV, 0.73 κ) to fair (AdV, 0.27 κ). Heterotypic seroresponses observed between PIV and persistent low-level AdV shedding may account for higher method discordance observed with each of these viruses. Serology can be a helpful adjunct to RT-PCR for research-based assessment of the etiologic contribution of non-influenza respiratory viruses to CAP.


Both molecular and serological assays have been used previously to determine the etiology of community-acquired pneumonia (CAP). However, the correlation of these methods and added diagnostic value of serology has not been fully evaluated. Using data from patients enrolled in the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, we compared real-time RT-PCR and serology for diagnosis of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza viruses 1-3 (PIV) and adenovirus (AdV) infections. Of 5126 patients enrolled, RT-PCR and serology test results were available for 2023, including 1087 children <18 years of age and 936 adults. For RSV, 287 (14.2%) patients were positive by RT-PCR and 234 (11.6%) were positive by serology; HMPV, 172 (8.5%) tested positive by RT-PCR and 147 (7.3%) by serology; PIVs, 94 (4.6%) tested positive by RT-PCR and 92 (4.6%) by serology; and AdV, 111 (5.5%) positive by RT-PCR and 62 (3.1%) by serology. RT-PCR provided the most positive detections overall, but serology increased diagnostic yield for RSV (by 11.8%), HMPV (by 25.0%), AdV (by 32.4%), and PIV (by 48.9%). Method concordance estimated by Cohen's kappa (κ) coefficient ranged from good (RSV, 0.73 κ) to fair (AdV, 0.27 κ). Heterotypic seroresponses observed between PIV and persistent low-level AdV shedding may account for higher method discordance observed with each of these viruses. Serology can be a helpful adjunct to RT-PCR for research-based assessment of the etiologic contribution of non-influenza respiratory viruses to CAP.


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