Diagnosis of Respiratory Syncytial Virus in Adults Substantially Increases When Adding Sputum, Saliva, and Serology Testing to Nasopharyngeal Swab RT–PCR

Abstract

Introduction Nearly all existing respiratory syncytial virus (RSV) incidence estimates are based on real-time polymerase chain reaction (RT–PCR) testing of nasal or nasopharyngeal (NP) swabs. Adding testing of additional specimen types to NP swab RT–PCR increases RSV detection. However, prior studies only made pairwise comparisons and the synergistic effect of adding multiple specimen types has not been quantified. We compared RSV diagnosis by NP swab RT–PCR alone versus NP swab plus saliva, sputum, and serology. Methods This was a prospective cohort study over two study periods (27 December 2021 to 1 April 2022 and 22 August 2022 to 11 November 2022) of patients aged ≥ 40 years hospitalized for acute respiratory illness (ARI) in Louisville, KY. NP swab, saliva, and sputum specimens were collected at enrollment and PCR tested (Luminex ARIES platform). Serology specimens were obtained at acute and convalescent timepoints (enrollment and 30–60-day visit). RSV detection rate was calculated for NP swab alone and for NP swab plus all other specimen type/test. Results Among 1766 patients enrolled, 100% had NP swab, 99% saliva, 34% sputum, and 21% paired serology specimens. RSV was diagnosed in 56 (3.2%) patients by NP swab alone, and in 109 (6.2%) patients by NP swab plus additional specimens, corresponding to a 1.95 times higher rate [95% confidence interval (CI) 1.62, 2.34]. Limiting the comparison to the 150 subjects with all four specimen types available (i.e., NP swab, saliva, sputum, and serology), there was a 2.60-fold increase (95% CI 1.31, 5.17) compared to NP swab alone (3.3% versus 8.7%). Sensitivities by specimen type were: NP swab 51%, saliva 70%, sputum 72%, and serology 79%. Conclusions Diagnosis of RSV in adults was several-fold greater when additional specimen types were added to NP swab, even with a relatively low percentage of subjects with sputum and serology results available. Hospitalized RSV ARI burden estimates in adults based solely on NP swab RT–PCR should be adjusted for underestimation. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00805-1.

Estimated Incidence of Hospitalizations and Deaths Attributable to Respiratory Syncytial Virus Infections Among Adults in Germany Between 2015 and 2019

“…The proportions of all respiratory infections attributable to RSV in our study (3–4%) are also similar to previous observational studies, which reported that 4–8% of symptomatic respiratory infections in adults age ≥ 60 years were caused by RSV [ 14 , 63 ]. The relatively similar values from our model-based approach and prospective study estimates that have been adjusted for reduced sensitivity of nasal/nasopharyngeal swab PCR [ 16 , 17 ] in adults provide support for the validity of our model structure.…”

“…For the first time, RSV vaccines were recently licensed to prevent lower respiratory tract disease caused by RSV in adults ≥ 60 years [ 12 , 15 ]. Yet, the incidence and clinical burden of RSV disease in adults are difficult to measure due to the lack of specific RSV symptomatology that could distinguish it from influenza and other respiratory viruses, limited standard-of-care RSV testing among adults, reduced sensitivity of diagnostic testing among adults [ 16 , 17 ], poor RSV diagnostic capacity in many healthcare facilities, and low public and medical community awareness of RSV in adults [ 18 – 21 ]. Furthermore, data on RSV burden in people with underlying conditions are sparse [ 4 , 21 , 22 ].…”

Exploring the potential of a saliva-based, RNA-extraction-free PCR test for the multiplexed detection of key respiratory pathogens

“…The concept of using saliva as a diagnostic tool for respiratory pathogens has gained widespread attention since being demonstrated as an acceptable and sensitive sample type for the detection of SARS-CoV-2 during the COVID-19 pandemic (Tobik et al, 2022). Adding to the global success of many saliva-based SARS-CoV-2 tests, a recent study by Ramirez et al (Ramirez et al, 2023) demonstrated the utility of saliva for RSV diagnosis. They observed that its inclusion alongside the gold-standard NPS resulted in a twofold increase in the diagnostic yield when compared to NPS alone.…”

Diagnostic testing preferences can help inform future public health response efforts: global insights from an international survey

“…24 In contrast, self-collectible samples like saliva and urine are cheaper and less invasive options requiring a fraction of the resources. 24 Combined with perceptions regarding the upper respiratory sample types, the acceptability of saliva may prove beneficial for diagnosing various infectious diseases, including SARS-CoV-2, MERS-CoV, Ebola, Zika, 23 influenza, 25 respiratory syncytial virus (RSV), 26 and more 27 in the developing world. 24 Several limitations exist in considering the broader applicability of the results in this study.…”