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      Low Levels of RSV Testing Among Adults Hospitalized for Lower Respiratory Tract Infection in the United States

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          Abstract

          Introduction

          Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI)-related hospitalizations in older adults. Without RSV-specific treatment for adults, testing is uncommon, leading to potential underestimation of RSV incidence in real-world data studies. This study aimed to quantify the frequency of RSV testing during LRTI-related hospitalizations of older adults to inform interpretation of incidence estimates.

          Methods

          Administrative and billing data for hospitalizations of adults aged ≥ 65 years with a primary or secondary diagnosis of LRTI during the 2016–2019 RSV seasons (October–April) were extracted from the US all-payer Premier Healthcare Database (PHD). Billing codes identified RSV tests administered during eligible hospitalizations. The proportion of LRTI-related hospitalizations with a billed RSV test was calculated for each hospital in PHD, and summarized descriptively by hospital bed size, teaching status, and population served.

          Results

          Most of the 937 study hospitals performed RSV testing infrequently during LRTI hospitalization; median percentage of LRTI hospitalizations with RSV testing was 4.3%, and 78.4% of hospitals performed RSV testing in less than 25% of LRTI-related hospitalizations. RSV testing varied extensively by hospital type. Median percentage tested was significantly higher for hospitals with ≥ 200 beds (9.1%) versus < 200 beds (1.6%), for teaching (11.0%) versus non-teaching (2.5%) hospitals, and in urban (7.4%) versus rural (0.7%) settings. The median percentage of RSV testing increased over time, from 0.8% to 6.3% between the 2016/17 and 2018/19 seasons.

          Conclusion

          A small proportion of older adults hospitalized with LRTI are tested for RSV in US hospitals. Large variability occurs across hospital types. Consequently, retrospective database analyses likely result in a substantial underestimation of the true RSV-related hospitalization incidence. RSV incidence studies using real-world data need to assess for RSV testing frequency and adjust their results for under ascertainment associated with limited testing.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40121-023-00758-5.

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          Most cited references17

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          Respiratory syncytial virus infection in elderly and high-risk adults.

          Respiratory syncytial virus (RSV) is an increasingly recognized cause of illness in adults. Data on the epidemiology and clinical effects in community-dwelling elderly persons and high-risk adults can help in assessing the need for vaccine development. During four consecutive winters, we evaluated all respiratory illnesses in prospective cohorts of healthy elderly patients (> or =65 years of age) and high-risk adults (those with chronic heart or lung disease) and in patients hospitalized with acute cardiopulmonary conditions. RSV infection and influenza A were diagnosed on the basis of culture, reverse-transcriptase polymerase chain reaction, and serologic studies. A total of 608 healthy elderly patients and 540 high-risk adults were enrolled in prospective surveillance, and 1388 hospitalized patients were enrolled. A total of 2514 illnesses were evaluated. RSV infection was identified in 102 patients in the prospective cohorts and 142 hospitalized patients, and influenza A was diagnosed in 44 patients in the prospective cohorts and 154 hospitalized patients. RSV infection developed annually in 3 to 7 percent of healthy elderly patients and in 4 to 10 percent of high-risk adults. Among healthy elderly patients, RSV infection generated fewer office visits than influenza; however, the use of health care services by high-risk adults was similar in the two groups. In the hospitalized cohort, RSV infection and influenza A resulted in similar lengths of stay, rates of use of intensive care (15 percent and 12 percent, respectively), and mortality (8 percent and 7 percent, respectively). On the basis of the diagnostic codes of the International Classification of Diseases, 9th Revision, Clinical Modification at discharge, RSV infection accounted for 10.6 percent of hospitalizations for pneumonia, 11.4 percent for chronic obstructive pulmonary disease, 5.4 percent for congestive heart failure, and 7.2 percent for asthma. RSV infection is an important illness in elderly and high-risk adults, with a disease burden similar to that of nonpandemic influenza A in a population in which the prevalence of vaccination for influenza is high. An effective RSV vaccine may offer benefits for these adults. Copyright 2005 Massachusetts Medical Society.
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            Respiratory syncytial virus: virology, reverse genetics, and pathogenesis of disease.

            Human respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand RNA virus of family Paramyxoviridae. RSV is the most complex member of the family in terms of the number of genes and proteins. It is also relatively divergent and distinct from the prototype members of the family. In the past 30 years, we have seen a tremendous increase in our understanding of the molecular biology of RSV based on a succession of advances involving molecular cloning, reverse genetics, and detailed studies of protein function and structure. Much remains to be learned. RSV disease is complex and variable, and the host and viral factors that determine tropism and disease are poorly understood. RSV is notable for a historic vaccine failure in the 1960s involving a formalin-inactivated vaccine that primed for enhanced disease in RSV naïve recipients. Live vaccine candidates have been shown to be free of this complication. However, development of subunit or other protein-based vaccines for pediatric use is hampered by the possibility of enhanced disease and the difficulty of reliably demonstrating its absence in preclinical studies.
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              Respiratory syncytial virus infection in older adults: an under-recognized problem.

              Human respiratory syncytial virus (RSV) is an enveloped, single-stranded, negative-sense RNA virus and member of the Paramyxoviridae family of the genus Pneumovirus that was first reported as a major pathogen in pediatric populations. However, since its discovery, RSV has not infrequently been detected in adults. Reinfection occurs throughout life, with more severe disease occurring in older adults, immunocompromised patients, and those with underlying cardiopulmonary disease. Initially described as the cause of nursing home outbreaks of respiratory disease, there is a now significant body of literature describing the clinical importance of RSV in older adults in a multitude of settings including long-term care, adult daycares, and in community-dwelling adults. Moreover, recent reports from China and other countries emphasize that RSV is a global pathogen that will become increasingly important in developed nations with aging populations. Annual attack rates in the USA range from 2 to 10% in community-dwelling older adults and 5-10% in older adults living in congregate settings. Population-based calculations of the proportion of acute respiratory illnesses attributable to RSV estimate that 11,000 elderly persons die annually in the USA of illnesses related to RSV infection. Clinical manifestations of RSV infections are similar to that of other viral respiratory pathogens and include cough, nasal congestion, rhinorrhea, sore throat, and dyspnea. Lower respiratory tract disease is common and may result in respiratory failure (8-13%) or death (2-5%). Recent advances in molecular diagnostics have made it possible to rapidly identify RSV infection using nucleic acid amplification tests, although clinicians will need to suspect the diagnosis when viral activity is high. At the present time, treatment is supportive. Effective antiviral agents for the treatment and vaccines for prevention of RSV remain a significant unmet medical need in the older adult population.
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                Author and article information

                Contributors
                Jennifer.Judy@pfizer.com
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Cheshire )
                2193-8229
                2193-6382
                27 January 2023
                27 January 2023
                : 1-9
                Affiliations
                [1 ]GRID grid.487416.8, Pfizer bv, ; Capelle aan den IJssel, The Netherlands
                [2 ]GRID grid.410513.2, ISNI 0000 0000 8800 7493, Pfizer Inc, ; New York, NY USA
                [3 ]GRID grid.512384.9, EVERSANA, ; Burlington, ON Canada
                [4 ]GRID grid.410513.2, ISNI 0000 0000 8800 7493, Pfizer Vaccines, ; Collegeville, PA USA
                [5 ]Pfizer Vaccines, Dublin, Ireland
                Author information
                http://orcid.org/0000-0001-6209-4370
                http://orcid.org/0000-0002-2246-9745
                http://orcid.org/0000-0002-4207-7554
                http://orcid.org/0000-0003-2392-8111
                http://orcid.org/0000-0002-1287-5416
                Article
                758
                10.1007/s40121-023-00758-5
                9883084
                36707466
                24d84908-ff65-40ab-860e-da234a6e0281
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 22 November 2022
                : 3 January 2023
                Categories
                Original Research

                lower respiratory tract infection (lrti),respiratory syncytial virus (rsv),rsv testing

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