title: Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia.
abstract: Both molecular and serological assays have been used previously to determine the etiology of community-acquired pneumonia (CAP). However, the extent to which these methods are correlated and the added diagnostic value of serology for respiratory viruses other than influenza virus have not been fully evaluated. Using data from patients enrolled in the Centers for Disease Control and Prevention (CDC) Etiology of Pneumonia in the Community (EPIC) study, we compared real-time reverse transcription-PCR (RT-PCR) and serology for the diagnosis of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus 1 to 3 (PIV1, PIV2, and PIV3), and adenovirus (AdV) infections. Of 5,126 patients enrolled, RT-PCR and serology test results were available for 2,023, including 1,087 children below the age of 18 years and 936 adults. For RSV, 287 (14.2%) patients were positive by RT-PCR and 234 (11.6%) were positive by serology; for HMPV, 172 (8.5%) tested positive by RT-PCR and 147 (7.3%) by serology; for the PIVs, 94 (4.6%) tested positive by RT-PCR and 92 (4.6%) by serology; and for AdV, 111 (5.5%) tested positive by RT-PCR and 62 (3.1%) by serology. RT-PCR provided the highest number of 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%). The method concordance estimated by Cohen's kappa coefficient (κ) ranged from good (for RSV; κ = 0.73) to fair (for AdV; κ = 0.27). Heterotypic seroresponses observed between PIVs and persistent low-level AdV shedding may account for the 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 respiratory viruses other than influenza virus to CAP.
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.|Battelle, Columbus, Ohio, USA.
authors: Yange
authors: Y
authors: Zhang
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.|Battelle, Columbus, Ohio, USA.
authors: Senthilkumar K
authors: SK
authors: Sakthivel
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Anna
authors: A
authors: Bramley
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Seema
authors: S
authors: Jain
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Amber
authors: A
authors: Haynes
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: James D
authors: JD
authors: Chappell
authors: University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
authors: Weston
authors: W
authors: Hymas
authors: Le Bonheur Children's Hospital, Memphis, Tennessee, USA.|University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors: Noel
authors: N
authors: Lenny
authors: Le Bonheur Children's Hospital, Memphis, Tennessee, USA.|University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors: Anami
authors: A
authors: Patel
authors: Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors: Chao
authors: C
authors: Qi
authors: University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
authors: Krow
authors: K
authors: Ampofo
authors: Le Bonheur Children's Hospital, Memphis, Tennessee, USA.|University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors: Sandra R
authors: SR
authors: Arnold
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Wesley H
authors: WH
authors: Self
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Derek J
authors: DJ
authors: Williams
authors: University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
authors: David
authors: D
authors: Hillyard
authors: Emory University School of Medicine, Atlanta, Georgia, USA.
authors: Evan J
authors: EJ
authors: Anderson
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Carlos G
authors: CG
authors: Grijalva
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Yuwei
authors: Y
authors: Zhu
authors: Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors: Richard G
authors: RG
authors: Wunderink
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Kathryn M
authors: KM
authors: Edwards
authors: University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
authors: Andrew T
authors: AT
authors: Pavia
authors: Le Bonheur Children's Hospital, Memphis, Tennessee, USA.|University of Tennessee Health Science Center, Memphis, Tennessee, USA.|St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Jonathan A
authors: JA
authors: McCullers
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA dde1@cdc.gov.
authors: Dean D
authors: DD
authors: Erdman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000175:diagnosis*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011024:Pneumonia, Viral / Q000175:diagnosis*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods*; D055815:Young Adult
keywords: PCR assays; PCR assays and serology; community-acquired pneumonia; respiratory virus infections; serology