Under-ascertainment of Respiratory Syncytial Virus infection in adults due to diagnostic testing limitations: A systematic literature review and meta-analysis

Chukwuemeka Onwuchekwa, Laura Mora Moreo, Sonia Menon, Belen Machado, Daniel Curcio, Warren Kalina, Jessica E Atwell, Bradford D Gessner, Mariana Siapka, Neha Agarwal, Michelle Rubbrecht, Harish Nair, Mark Rozenbaum, Zuleika Aponte-Torres, Hilde Vroling, Elizabeth Begier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

BACKGROUND: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection.

METHODS: EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types.

RESULTS: Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable.

CONCLUSIONS: RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.

Original languageEnglish
Pages (from-to)173-184
Number of pages12
JournalThe Journal of Infectious Diseases
Issue number2
Early online date20 Jan 2023
Publication statusPublished - 14 Jul 2023

Keywords / Materials (for Non-textual outputs)

  • respiratory syncytial virus infections
  • adults
  • diagnosis
  • epidemiology
  • sensitivity and specificity


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