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

Zhang Y1,2, Sakthivel SK1,2, Bramley A1, Jain S1, Haynes A1, Chappell JD3, Hymas W4, Lenny N5,6, Patel A5,6, Qi C7, Ampofo K4, Arnold SR5,6, Self WH3, Williams DJ3, Hillyard D4, Anderson EJ8, Grijalva CG3, Zhu Y3, Wunderink RG7, Edwards KM3, Pavia AT4, McCullers JA5,6,9, Erdman DD10.

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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.