Syncytial Virus In Adults Research Articles

Burden of Disease Due to Respiratory Syncytial Virus in Adults in Five Middle-Income Countries.

Respiratory syncytial virus (RSV) is an important cause of severe respiratory disease in older adults. Understanding the disease burden is crucial for guiding vaccination policy and raising disease awareness. We estimated the burden of RSV hospitalizations and deaths in adults in five middle-income countries: Argentina, Brazil, Chile, Mexico, and Malaysia. Hospital discharge and death statistics due to any respiratory disease (ICD-10 codes: J00-99) from 2010 to 2022 were obtained. The RSV attributable burden on hospitalizations and deaths by age group was determined for 2019 using previously published estimates. Latin American countries showed distinct annual peaks in respiratory-related hospitalizations and deaths during winter months that were absent in Malaysia. Among ≥20-year-olds in 2019, there were 14,604 RSV-attributable hospitalizations nationally in Argentina, 44,323 in Brazil, 4529 in Chile, 7416 in Malaysia, and 8651 in Mexico, and 60-74% in ≥65-year-olds. There were also 3518 RSV-attributable deaths in Argentina, 9115 in Brazil, 801 in Chile, 704 in Malaysia, and 3806 in Mexico 79-88% in ≥65-year-olds. Incidences of RSV-attributable hospitalizations in ≥75-year-olds ranged between 256.3 and 294.3 per 100,000 population, and deaths between 33.6 and 112.9 per 100,000 population. RSV is associated with a substantial disease burden beyond pediatric age groups, and preventive vaccines could have a major impact on this burden, especially in older adults.

Economic burden of respiratory syncytial virus in adults in Germany – a health claims analysis between 2015 and 2018

Aims Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) in infants and adults. While the clinical burden was recently estimated in adults in Germany, little is known about the economic burden. To fill this gap, this study aimed to assess hospital and outpatient healthcare resource utilization (HRU) and costs of RSV infections in adults in Germany. Methods In this retrospective, observational study on nationwide, representative, anonymized claims data (2015–2018), we identified patients ≥18 years with ICD-10-GM-codes specific to RSV (“RSV-specific”). To increase sensitivity, patients with unspecified LRTIs (including unspecified bronchitis, bronchiolitis, bronchopneumonia, and pneumonia) during RSV seasons were also included as cases potentially caused by RSV (“RSV-possible”). RSV-related HRU (hospital days, ICU and ventilation treatment, drug dispensation) and direct costs were estimated per episode. Excess costs per episode and for follow-up periods were compared to a matched control cohort. All outcomes were reported per healthcare sector and stratified by age and risk groups as well as disease severity (ICU admission/ventilation). Results Direct inpatient and outpatient mean episode costs were 3,473€ and 82€, respectively, with substantially higher costs for severe cases requiring intensive care and/or ventilation (10,801€). Direct costs for RSV-specific cases were higher than for RSV-possible cases (inpatients: 6,247€ vs. 3,450€; outpatients: 127€ vs. 82€). Moreover, costs were significantly higher for RSV patients than for controls and increased over time (inpatients: 5,140€ per episode vs 10,093€ per year; outpatients: 46€ per quarter vs 114€ per year). Limitations While the number of RSV-specific cases was low, inclusion of seasonal LRTI cases likely increased the sensitivity to detect RSV cases and allowed a better estimation of the total costs of RSV. Conclusions The economic burden of RSV-LRTI in adults in Germany is substantial, persists long-term, and is particularly high in the elderly. This highlights the need for cost-effective prevention measures.

The Changing Detection Rate of Respiratory Syncytial Virus in Adults in Western Australia between 2017 and 2023.

The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.

The Annual Economic Burden of Respiratory Syncytial Virus in Adults in the United States.

Current estimates of the economic burden of respiratory syncytial virus (RSV) are needed for policymakers to evaluate adult RSV vaccination strategies. A cost-of-illness model was developed to estimate the annual societal burden of RSV in US adults aged ≥60 years. Additional analyses were conducted to estimate the burden of hospitalized RSV in all adults aged 50-59 years and in adults aged 18-49 years with potential RSV risk factors. Among US adults aged ≥60 years, the model estimated 4.0 million annual RSV cases (95% uncertainty interval [UI], 2.7-5.6 million) and an annual economic burden of $6.6 billion (95% UI, $3.1-$12.9 billion; direct medical costs, $2.9 billion; indirect costs, $3.7 billion). The 4% of RSV cases that were hospitalized contributed to 94% of direct medical costs. Additional analyses estimated $422 million in annual hospitalization costs among all adults aged 50-59 years. Among adults aged 18-49 years with RSV risk factors, annual per capita burden was highest among people with congestive heart failure at $51 100 per 1000 people. The economic burden of RSV is substantial among adults aged ≥50 years and among adults aged 18-49 years with RSV risk factors, underscoring the need for preventive interventions for these populations.

Clinical Phenotypes and Molecular Characteristics of Respiratory Syncytial Virus in Adults: A Monocentric Prospective Study Between 2019 and 2022.

Respiratory syncytial virus (RSV) infection is a major cause of pneumonia in adults. Little is known on the viral genetic diversity and the associated clinical phenotypes in this population. This single-center prospective cohort study included RSV-infected patients hospitalized between January 2019 and December 2022. Of 100 patients, including 41 with severe infection, 72 were infected with RSV-B. RSV genome sequencing showed no clustering according to severity. Patients infected with RSV-B with risk factors for severe pneumonia had significantly higher fusion protein diversity scores. No amino acid substitutions conferring resistance to nirsevimab were detected.

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

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. 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 ≥ 40years 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. 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%. 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.

371. Adding sputum and saliva to nasopharyngeal swab samples for PCR detection of Respiratory Syncytial Virus in adults hospitalized with acute respiratory illness may double case detection

Abstract Background In hospitalized patients, nasopharyngeal (NP) swabs are the most common samples obtained for Respiratory Syncytial Virus (RSV) PCR testing. However, adding sputum is known to increase diagnostic yield, and saliva has been successfully used for viral respiratory infection diagnosis. We sought to compare RSV prevalence detected by PCR testing of NP swab alone versus NP swab plus saliva and sputum in adult patients hospitalized with acute respiratory illness (ARI). Methods This ongoing, prospective cohort study enrolled patients aged ≥40 years hospitalized for ARI in 4 hospitals in Louisville, Kentucky (Season 1: 27 Dec 21 – 1 Apr 22). NP swab, saliva, and sputum samples were obtained at enrollment or scavenged from standard-of-care specimens (all collected ≤3 days of admission), and PCR tested with Luminex ARIES FluA/B/RSV platform. We produced Venn diagrams of RSV positive samples by sample type for all patients and restricted to those with all 3 sample types. RSV prevalence for NP swab alone was calculated as number of patients with RSV-positive NP swabs divided by total number of patients tested. RSV prevalence by NP swab plus saliva and sputum was calculated as number of patients with RSV-positive NP swab, saliva, or sputum samples divided by total number of patients tested. Results We enrolled 653 patients and collected NP swabs (100% of patients), saliva (96%), and sputum (43% overall and 93% of the 303 sputum-producing patients). Among all patients, 28 patients tested RSV positive (Figure 1A), and when restricted to those with all 3 samples (Figure 1B), 14 tested positive. The overall cohort’s RSV prevalence by NP swab alone was 1.8% (12/653) and by NP swab plus saliva and/or sputum was 4.3% (28/653): 2.33 times higher with addition of saliva and sputum samples. Among patients with all 3 specimen types, the RSV prevalence increase was the same, and none were positive by NP swab only. Figure 1.Venn diagrams of positive RSV PCR tests (Left) A. Positive RSV PCR tests for 653 patients in overall cohort (Right) B. Positive RSV PCR tests for 275 patients with all 3 samples obtained. Conclusion RSV was most commonly detected in saliva samples. Current standard-of-care utilizing NP swab for RSV PCR testing appears to underestimate true RSV prevalence in hospitalized adult patients with ARI by more than 2-fold. Disclosures Alan Junkins, PhD, D(ABMM), Biomerieux: Advisor/Consultant Paul S. Schulz, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria Robin Hubler, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds|Pfizer, Inc: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds|Pfizer, Inc: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: I am a full time employee of Pfizer and hold Pfizer stocks Bradford D. Gessner, M.D., M.P.H., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds.

EE63 Economic Burden of Respiratory Syncytial Virus in Adults in the United States

EE63 Economic Burden of Respiratory Syncytial Virus in Adults in the United States

The burden of respiratory syncytial virus in adults: a systematic review and meta-analysis.

Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in young children. RSV is also a major viral pathogen causing severe lung disease in the adult population, particularly among the elderly. We conducted a review of adult RSV studies published from January 1970 to February 2017 to determine the burden of disease among adults worldwide. There were no restrictions on health care setting or definition of RSV infection. A total of 1530 published studies were identified, 95 of which were included in this review. The incidence rates of hospitalised RSV acute respiratory tract infection (ARI) in adults >65 years old ranged from 7.3 to 13.0/105 population in Africa and Asia and from 190 to 254/105 population in the USA. Higher incidence rates (195-1790/105 population) were observed in adults ≥50 years old for outpatient or emergency visits in the USA. Of all ARI patients, RSV accounted for 1-10% in adults and 2-14% in patients with chronic diseases or transplantation. Given the limitations in the existing data, significant efforts should be made to generate evidence on the burden of RSV infections in adults and to estimate the potential impact of future preventive interventions.

Respiratory syncytial virus in adults with severe acute respiratory illness in a high HIV prevalence setting

There are limited data on the epidemiology of respiratory syncytial virus (RSV) illness in HIV-infected adults or the elderly in Africa. We studied the epidemiology of RSV-associated severe acute respiratory illness (SARI) hospitalizations in adults in South Africa from 2009 through 2013. Individuals admitted to sentinel surveillance hospitals were investigated by respiratory tract swabs for RSV, using a multiplex real-time polymerase chain reaction assay. The incidence of RSV-associated SARI was calculated for the one site with population denominators. Of 7796 participants investigated, 329 (4%) tested positive for RSV. On multivariable analysis, HIV-infected individuals with RSV-associated SARI had greater odds of being in the age groups 18-44 and 45-64 years (odd ratios (OR) 26.3; 95% confidence interval (CI) 6.2-112.1 and OR 11.4; 95% CI 2.6-50.0) compared with those ≥65 years and being female (OR 2.7; 95% CI 1.4-5.4). The relative risk of hospitalization with RSV-associated SARI was 12-18 times higher in HIV infected individual compared to that of HIV-uninfected. The incidence of RSV-associated SARI was higher in HIV-infected individuals and those aged 65 years and older. Further studies are warranted to describe the disease association of RSV detected in adults with SARI.

Diagnostic tests for influenza and other respiratory viruses: determining performance specifications based on clinical setting

The lack of sensitivity of rapid immunoassays in detecting the novel 2009 H1N1 influenza virus infection has led to recommendations on influenza diagnostic testing for clinicians treating patients as well as advising clinicians on testing decisions. Studies have also shown that rapid immunoassays for seasonal influenza virus show considerable variability in performance characteristics, based on age of patient, prevalence of disease, course of infection, and the quality of the kit used. While public health authorities are currently focused on influenza virus diagnostics, a lack of sensitivity of rapid immunoassays for other viral respiratory pathogens has been widely reported, such as the very limited value of rapid immunoassays for the detection of respiratory syncytial virus in adults. In light of the lack of sensitivity of diagnostic tests for suspected 2009 H1N1 influenza virus infection, as well as their variable performance characteristics for seasonal influenza virus, a number of recommendations have been made by public health authorities advising clinicians on the need for clinical judgment as an important part of testing and treatment decisions as well as reliance on local epidemiologic and surveillance data. With the availability of new molecular methodologies that are user-friendly and allow the front-line physician as well as hospital infection control programs to significantly improve respiratory viral diagnostics, there is a need to carefully determine the most optimal diagnostic testing methodology based on the clinical setting. This review will describe the historical, current, and changing dynamics of respiratory virus infection diagnostics.

Respiratory syncytial virus infection in adults

Respiratory syncytial virus has increasingly been recognized as a clinically significant cause of respiratory tract infections in adults, especially among the elderly and the immunocompromised. Advances in molecular diagnostic methods have enabled rapid diagnosis of respiratory syncytial virus for clinical and epidemiological studies. Recent reports focus on clinical, immunological, and/or radiographic characterizations of respiratory syncytial virus infection in adults, particularly in hospitalized patients and those with underlying chronic obstructive pulmonary disease, and therapeutic and prophylactic use of antiviral agents in immunocompromised adults. Respiratory syncytial virus vaccine development remains a high priority, with the testing of genetically engineered live attenuated vaccines leading to further insights into the pathogenesis of respiratory syncytial virus in adults. Further studies are necessary to elucidate the pathogenesis and immune response against respiratory syncytial virus in adults. The significant burden of respiratory syncytial virus-induced disease in adults and the limited number of approved antiviral agents reinforce the need to develop a respiratory syncytial virus vaccine.

Detection of Respiratory Syncytial Virus in Adults with Chronic Obstructive Pulmonary Disease

Recently, respiratory syncytial virus (RSV) RNA has been identified by reverse transcriptase-polymerase chain reaction (RT-PCR) from a high percentage of patients with stable chronic obstructive pulmonary disease (COPD). These data raise the possibility of persistent low-grade infection in this population, which could have implications in COPD pathogenesis. RSV persistence was investigated by testing respiratory secretions from subjects with COPD during illness and at regular intervals over 1 yr. Nasal and sputum samples from subjects with COPD were tested by one-tube nested RT-PCR for RSV every 2 mo and during respiratory illnesses for 1 yr. Subjects positive for RSV were evaluated weekly until negative in two consecutive samples. Nasal secretions and serum were tested for RSV antibody. A rise of fourfold or greater was defined as evidence of RSV infection. A total of 112 patients were enrolled and the illnesses of 92 patients were evaluated. RSV was detected by RT-PCR in 6/92 (6.5%) illness nasal samples versus 0/685 routine nasal samples and in 5/69 (7.2%) illness sputum samples versus 3 /315 (0.9%) routine. Four additional RSV infections were identified by serum antibody responses. Of the RSV infections 86% were associated with serum or nasal antibody responses and 73% had symptoms of acute respiratory illness. Most RSV infections in patients with COPD are associated with symptomatic respiratory illnesses and measurable immune responses. Our data do not support the concept of RSV persistence in this population.

Cytokine gene polymorphisms moderate responses to respiratory syncytial virus in adults

Immune responses and illness severity during viral upper respiratory infections may be influenced by the local elaboration of cytokines. Cytokine gene polymorphisms moderate immune responses and severity of illness in various inflammatory and infectious diseases. We performed cytokine genotyping on 29 adults experimentally inoculated with respiratory syncytial virus (RSV) to determine whether specific cytokine gene polymorphisms are associated with immune responses or illness severity. DNA was extracted from leukocytes and assayed for TNF-α, IFN-γ, IL-6, IL-10 and TGF-β1 genotypes using polymerase chain reaction–sequence-specific primer technology. Outcomes consisted of baseline and convalescent RSV-specific serum IgG and nasal IgA titers, nasal secretion weights, nasal, throat and general symptom scores, and nasal cytokine protein levels. IFN-γ genotype was directly related with the frequency of subjects having at least a four-fold increase in RSV-specific serum IgG and TNF-α genotype was inversely associated with the frequency of subjects having at least a twofold increase in RSV-specific nasal IgA. Additionally, IL-6 genotype was predictive of certain measures of illness expression, while IFN-γ genotype predicted IL-1 protein levels, and TNF-α genotype predicted IL-6 and IL-8 protein levels in nasal lavage fluids. There were no associations between IL-10 or TGF-β1 and any of the outcome parameters. These results suggest that certain cytokine gene polymorphisms moderate immune responses and illness severity in adults experimentally exposed to RSV.

Incidence, etiologic pathogens, and diagnostic testing of community-acquired pneumonia.

Determination of the etiologic pathogens of community-acquired pneumonia has been problematic because of the lack of reliable rapid laboratory diagnostic tools as well as the controversy concerning diagnostic criteria. In the studies reviewed here, a specific pathogen was identified in 39% to 88% of patients. Streptococcus pneumoniae remains the most common cause of community-acquired pneumonia. Depending on the demographics of the study, between 2% to 43% of cases have been attributed to legionella or Chlamydia pneumoniae. More recently, other pathogens have emerged, including respiratory syncytial virus in adults, hantavirus, and possibly legionella-like amoebal pathogens and Streptococcus milleri group. Treatment guidelines published by various societies of experts have been helpful, but they cannot replace the need for better and rapid diagnostic techniques.

Evaluation of a temperature-sensitive mutant of respiratory syncytial virus in adults.

A temperature-sensitive {ts) mutant of respiratory syncytial virus, which was unable to replicate at 37 C in vitro, was administered by the nasopharyngeal route to adults who had low levels of neutralizing antibody in their nasal secretions. The ts mutant appeared to be attenuated under these conditions as indicated by a decrease in infectivity and by the asymptomatic nature of the infections that occurred. The ts mutant was genetically stable in vivo, and there was no evidence of reversion to wild type after replication in the upper respiratory passages of the volunteers. Although the mutant appeared to be attenuated, it did induce a state of resistance to subsequent challenge with wild-type (virulent) virus. These encouraging results suggest that the ts mutant should be further evaluated as a candidate for a vaccine for prevention of serious respiratory syncytial viral disease in the lower respiratory tract of young infants.