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

BACKGROUND: Most observational population-based studies identify RSV by nasal/nasopharyngeal swab RT-PCR only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based under-ascertainment of adult RSV infection. METHODS: EMBASE, PubMed and Web of Science were searched (Jan2000-Dec2021) 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 (pooled sensitivity, 64%), direct fluorescent antibody (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