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

Yange Zhang, Senthilkumar K Sakthivel, Anna Bramley, Seema Jain, Amber Haynes, James D Chappell, Weston Hymas, Noel Lenny, Anami Patel, Chao Qi, Krow Ampofo, Sandra R Arnold, Wesley H Self, Derek J Williams, David Hillyard, Evan J Anderson, Carlos G Grijalva, Yuwei Zhu, Richard G Wunderink, Kathryn M Edwards, Andrew T Pavia, Jonathan A McCullers, Dean D Erdman, Yange Zhang, Senthilkumar K Sakthivel, Anna Bramley, Seema Jain, Amber Haynes, James D Chappell, Weston Hymas, Noel Lenny, Anami Patel, Chao Qi, Krow Ampofo, Sandra R Arnold, Wesley H Self, Derek J Williams, David Hillyard, Evan J Anderson, Carlos G Grijalva, Yuwei Zhu, Richard G Wunderink, Kathryn M Edwards, Andrew T Pavia, Jonathan A McCullers, Dean D Erdman

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.

Keywords: PCR assays; PCR assays and serology; community-acquired pneumonia; respiratory virus infections; serology.

Copyright © 2016 American Society for Microbiology.

Figures

FIG 1
FIG 1
Box-and-whisker plots of CT values of RT-PCR-positive respiratory specimens, comparing patients with different seroresponse statuses. Whiskers mark the 10th and 90th percentiles, and boxes are bounded by the 25th and 75th percentiles, with bisecting lines representing median CT values. The sample size (N) is indicated for each category. Differences (Δ) in median CT values for each category are given, as well as P values calculated by the Mann-Whitney U test.
FIG 2
FIG 2
Temporal distribution of serology- and RT-PCR-positive test results (colored bars) superimposed on CDC National Respiratory and Enteric Virus Surveillance System (NREVSS) regional surveillance data for each of the viruses studied. The NREVSS data shown here were collected on a weekly basis between January 2010 and June 2012 from reporting centers located in the metropolitan areas of the four cities where the EPIC study was conducted.

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