RSV Testing Research Articles

Laboratory confirmation of respiratory syncytial virus infection is not associated with increased risk of death in adults with acute respiratory illness

Abstract Background Limited data have described the testing patterns and outcomes of adults (≥18 years) with acute respiratory illness (ARI) in the emergency department (ED) setting. Methods This prospective cohort study includes ARI patients from the CDC-sponsored Respiratory Virus Laboratory Emergency Department Network Surveillance (RESP-LENS) program from August 2021 until March 2024 (n=91 hospitals). Patients with ARIs were identified weekly by electronic surveillance for one or more of 130 ICD-10 codes that defined ARI. Patients were followed for 30 days for the primary outcomes of hospitalization and mortality. Testing for RSV with nasopharyngeal swabbing followed by was done as part of usual care. Risk of 30-day mortality RSV positivity was tested in a generalized estimating equation (GEE). Findings From 1,210,394 patients with ARI, 345,185 (28.5%) adults underwent RSV testing, which was positive in 2.4%. In RSV+ adults the overall mortality rate was 1.9% compared with a mortality rate of 2.9% in RSV- adults. Mortality with RSV+ increased with age ≥65 years: 3.8% (95% CI: 3.1 to 4.5%). However, in the GEE, RSV+ status was not associated with higher rate of hospitalization (adjusted Odds 0.79, 0.75-0.84), or 30-day mortality (odds 0.62, 0.53-0.74) relative to those who were RSV-. Age ≥65 years, incremental worsening of vital signs, male sex and heart failure were independently associated with death. Conclusion Among adults with ARI presenting to an ED and who were tested for RSV as part of their usual care, laboratory-confirmed RSV positivity was not associated with increased risk, including hospitalization, ICU requirement, or death.

Burden of disease and cost of illness of infants less than 6 months of age hospitalised with respiratory syncytial virus in Denmark – a 10-year national register-based study

BackgroundRespiratory syncytial virus (RSV) is the most common cause of hospitalisation in infants aged ≤ 6 months in Western countries. Nearly 1,500 infants under six months of age are hospitalised with RSV annually in Denmark. This nationwide study describes the healthcare resource utilisation and costs related to RSV hospitalisation in this vulnerable age group.MethodsRSV cases were identified in the Danish National Patient Register. Infants were included if they at the age of 0–5 months had a (1) respiratory related hospital admission (duration > 12 h), (2) within 10 days of a positive RSV test, (3) between January 2013 and December 2022. Each case was matched with five individuals never diagnosed with RSV on age, sex, region of residence, birth (pre/full term), number of siblings < 7 years old, and parents’ education. An episode of RSV was defined as the seven days prior to hospitalisation to 30 days after initial hospitalisation. Study outcomes included contacts with hospital and primary care, and total healthcare costs defined as the sum cost of hospital care, primary care, and prescription medicine. Cost and contacts attributable to RSV was calculated in a diff-in-diff framework, as the difference between case and reference group.ResultsThe study population comprised of 8,428 RSV cases and 41,725 reference individuals. Cases generated 1.58 (p < 0.001) attributable inpatient contacts, 0.84 (p < 0.001) outpatient contacts, and 1.19 (p < 0.001) primary care contacts during their RSV episode. An additional 0.6 (p < 0.001) inpatient, 1.08 (p < 0.001) outpatient and 2.42 (p < 0.001) primary care contacts were attributed to RSV in the year following the RSV episode. Total cost of an RSV episode was EUR 2,997 (p < 0.001) with an additional EUR 1,428 (p < 0.001) in the following year.ConclusionRSV hospitalisations of infants are associated with substantial healthcare utilisation and costs. The same pattern was observed in the year following the RSV episode. If the new RSV prevention options are introduced nationwide, the overall burden of RSV is expected to be substantially reduced in the future.

2475. Admissions Screening for Influenza and RSV Among a Highly Immunosuppressed Patient Population

Abstract Background During the Fall/Winter 2022-23, the U.S. experienced an early surge of Influenza and RSV cases, while SARS-CoV-2 cases persisted. With concerns of a potential “tripledemic” on the horizon, the NIH Clinical Center, a clinical research hospital with a heavily immunosuppressed patient population, implemented Influenza and RSV testing, in addition to SARS-CoV-2, for all patients on admission to facilitate early detection and prompt isolation of infected patients. Methods Nasopharyngeal (NP) swabs (n=1213) were collected on admission from 11/2022 to 4/2023 and tested for Influenza and RSV by PCR. 1213 NP swabs from 985 unique patients were tested (some patients had multiple admissions); 1100 were tested on the Panther Fusion® SARS-CoV-2 Assay (Hologic, Inc.) and 113 using the SARS-CoV-2 RT-PCR Xpert® Xpress test. Medical chart reviews and discussions with patient care providers elucidated whether cases identified on admission were asymptomatic. Results Of 1213 NP swabs collected from patients admitted to our hospital, 5 (0.41%) were identified with Influenza A infection, 4 (0.33%) RSV infection and no patients were identified with Influenza B. Two (0.16%) had a known history of RSV infection, 3 (0.25%) screened negative for symptoms but subsequently disclosed symptoms, 1 (0.08%) was asymptomatic on admission but disclosed a recent history of an upper respiratory infection, and 3 were asymptomatic. All infections were detected between late November 2022 to mid-January 2023, when community transmission was high, yielding a 2-month positivity rate of 2.3% during this time of peak community spread. Conclusion Admission surveillance for Influenza and RSV during a respiratory virus surge in our community allowed us to isolate nine patients on admission who would likely not have been appropriately isolated, as symptom screening alone is not reliable. Surveillance is important to be able to identify infected patients promptly when respiratory infections are rampant in the community, and especially for institutions serving immunosuppressed patients. Disclosures All Authors: No reported disclosures

Determining the true incidence of seasonal respiratory syncytial virus-confirmed hospitalizations in preterm and term infants in Western Australia

Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model incorporating pre-pandemic RSV testing data and hospital admission data to estimate infant RSV-hospitalizations by birth month and prematurity, focused on infants aged <1 year. The overall predicted RSV-hospitalization incidence rates in infants <6 months were 32.7/1,000 child-years (95 % CI: 31.8, 33.5) and 3.1/1,000 child-years (95 % CI: 3.0, 3.1) in infants aged 6-<12 months. Predicted RSV-hospitalization rates for infants aged <6 months were highest for infants born in April/May. Predicted rates for preterm infants born 29–32 weeks gestation were highest in March-May, whereas infants born >33 weeks had peak RSV-hospitalization rates from May-June, similar to late preterm or term births. RSV-hospitalization rates in the pre-pandemic era were highly seasonal, and seasonality varied with degree of prematurity. Accurate estimates of RSV-hospitalization in high-risk sub-groups are essential to understand preventable burden of RSV especially given the current prevention landscape.

Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children.

Various case definitions of respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) are currently proposed. We assessed the performance of 3 clinical case definitions against the World Health Organization definition recommended in 2015 (WHO 2015). In this prospective cohort study conducted in 8 countries, 2401 children were followed up for 2 years from birth. Suspected LRTIs were detected via active and passive surveillance, followed by in-person clinical evaluation including single timepoint respiratory rate and oxygen saturation (by pulse oximetry) assessment, and nasopharyngeal sampling for RSV testing by polymerase chain reaction. Agreement between case definitions was evaluated using Cohen's κ statistics. Of 1652 suspected LRTIs, 227 met the WHO 2015 criteria for RSV-LRTI; 73 were classified as severe. All alternative definitions were highly concordant with the WHO 2015 definition for RSV-LRTI (κ: 0.95-1.00), but less concordant for severe RSV-LRTI (κ: 0.47-0.82). Tachypnea was present for 196/226 (86.7%) WHO 2015 RSV-LRTIs and 168/243 (69.1%) LRTI/bronchiolitis/pneumonia cases, clinically diagnosed by nonstudy physicians. Low oxygen saturation levels were observed in only 55/226 (24.3%) WHO 2015 RSV-LRTIs. Three case definitions for RSV-LRTI showed high concordance with the WHO 2015 definition, while agreement was lower for severe RSV-LRTI. In contrast to increased respiratory rate, low oxygen saturation was not a consistent finding in RSV-LRTIs and severe RSV-LRTIs. This study demonstrates that current definitions are highly concordant for RSV-LRTIs, but a standard definition is still needed for severe RSV-LRTI. NCT01995175.

Rapid antigen test for adenovirus in children: Age and onset of symptoms are important

IntroductionRespiratory infection is the most common human adenovirus (HAdV) disease accounting for 7–8% of viral respiratory diseases in children less than 5 years. Differentiation of bacterial infections and viral infections is a common clinical problem. Material and methodsOne hundred oropharyngeal swabs obtained from October 2019 to November 2020 from patients attending the paediatric emergency room with suspicion of upper respiratory tract infection and negative results in influenza and RSV tests were included. Oropharyngeal swabs specimens were rapidly processed with STANDARD™ F Adeno Respi Ag FIA and the results were confirmed by RealStar® Adenovirus PCR Kit 1.0 (Altona diagnostics). ResultsSTANDARD™ F Adeno Respi Ag FIA had sensitivity and specificity values of 71.93% and 100% respectively. The performance of the test was higher in samples from children younger than 24 months and taken less than 72h since the beginning of symptoms. In this subgroup the test had 88.8% sensitivity and 100% specificity. ConclusionSTANDARD™ F Adeno Respi Ag FIA may improve the management of respiratory diseases in children younger than 24 months and less than 72h since the beginning of symptoms in paediatric emergency rooms.

Rapid antigen test for adenovirus in children: Age and onset of symptoms are important

IntroductionRespiratory infection is the most common human adenovirus (HAdV) disease accounting for 7–8% of viral respiratory diseases in children less than 5 years. Differentiation of bacterial infections and viral infections is a common clinical problem. Material and methodsOne hundred oropharyngeal swabs obtained from October 2019 to November 2020 from patients attending the paediatric emergency room with suspicion of upper respiratory tract infection and negative results in influenza and RSV tests were included. Oropharyngeal swabs specimens were rapidly processed with STANDARD™ F Adeno Respi Ag FIA and the results were confirmed by RealStar® Adenovirus PCR Kit 1.0 (Altona diagnostics). ResultsSTANDARD™ F Adeno Respi Ag FIA had sensitivity and specificity values of 71.93% and 100% respectively. The performance of the test was higher in samples from children younger than 24 months and taken less than 72h since the beginning of symptoms. In this subgroup the test had 88.8% sensitivity and 100% specificity. ConclusionSTANDARD™ F Adeno Respi Ag FIA may improve the management of respiratory diseases in children younger than 24 months and less than 72h since the beginning of symptoms in paediatric emergency rooms.

1897. The Decline of Respiratory Viruses During the SARS-CoV-2 Pandemic: Public Health Interventions vs. Viral Competition?

Abstract Background With the spread of the SARS-CoV-2 pandemic in 2020 and the attendant global precautions such as masking, travel restrictions and social distancing, the WHO FluNet data indicated a decline in flu rates. The CDC data for the 2020-2021 season showed the same decline in US flu as well as other respiratory viruses. Two hypotheses to explain the observed phenomenon are the impact of non-pharmaceutical interventions (NPI) to prevent SARS-CoV-2 infection and suppression of other respiratory viruses by SARS-CoV-2 through a form of resource competition. Methods We conducted a study using the EPIC Slicer Dicer analytics tool and the Yale Internal Medicine COVID-19 Database to retrieve data from the Yale New Haven Health System (YNHHS). We tabulated the total number of positive and negative tests for SARS-CoV-2 and a panel of respiratory viruses from September 2, 2018 to April 30, 2022 to cover pre- and peri-pandemic periods. These results were divided into three age groups: ≤12, 13-59, and ≥60. Epidemic curves of each virus with respect to each other, the season, and the introduction of NPIs were constructed to help differentiate between the two hypotheses. Results Pre-pandemic data from 09/2018 to 02/2020 revealed seasonal spikes in influenza A and B with 254 positive weekly influenza A/B tests from 11/2018 to 02/2019 for a positivity rate of 7.97% and 481 positive weekly tests (10.53% positivity rate [PR]) from November 2019 to February 2020. There were only 0.35 positive weekly influenza A/B tests (0.05% PR) from 11/2020 to 02/2021 with 2018 positive weekly tests (6.45% PR) for SARS-CoV-2 over the same period. From 11/2020 to 02/2021, there were 56 positive weekly influenza A/B tests (1.44% PR) and 4347 positive weekly SARS-CoV-2 tests (10.35% PR). From 07/2021 to 11/2021, there was an increased rate of positive RSV tests (82 per week, 15.76% PR) and rhinovirus tests (58 per week, 18.73% PR). There were 803 positive weekly tests (2.53% positivity rate) for SARS-CoV-2 over this same period. Conclusion Since the start of the SARS-CoV-2 pandemic, the number of positive tests for influenza A/B and seasonal respiratory viruses have not reached pre-pandemic levels across the YNHHS. However, rates of influenza and other respiratory viruses have increased since the relaxation of NPIs. Disclosures All Authors: No reported disclosures.

Systematic Literature Review of Respiratory Syncytial Virus Laboratory Testing Practices and Incidence in United States Infants and Children

BackgroundRespiratory syncytial virus (RSV) can cause serious illness in those aged <5 years in the United States, but uncertainty remains around which populations receive RSV testing. We conducted a systematic literature review of RSV testing patterns in studies published from 2000 to 2021.MethodsStudies of RSV, medically attended RSV lower respiratory tract infections (LRTIs), and bronchiolitis were identified using standard methodology. Outcomes were clinical decisions to test for RSV, testing frequency, and testing incidence proportions in inpatient (IP), emergency department (ED), outpatient (OP), and urgent care settings.ResultsEighty good-/fair-quality studies, which reported data from the period 1988–2020, were identified. Twenty-seven described the clinical decision to test, which varied across and within settings. Two studies reported RSV testing frequency for multiple settings, with higher testing proportions in IP (n = 2, range: 83%–85%, 1996–2009) compared with ED (n = 1, 25%, 2006–2009) and OP (n = 2, 15%–25%, 1996–2009). Higher RSV testing incidence proportions were observed among LRTI infant populations in the ED (n = 1, 74%, 2007–2008) and OP (n = 2, 54%–69%, 1995–2008). Incidence proportions in LRTI populations were not consistently higher in the IP setting (n = 13). Across studies and time, there was heterogeneity in RSV testing patterns, which may reflect varying detection methods, populations, locations, time periods, and healthcare settings.ConclusionsNot all infants and children with LRTI are tested for RSV, highlighting underestimation of RSV burden across all settings.

RSV testing practice and positivity by patient demographics in the United States: integrated analyses of MarketScan and NREVSS databases

BackgroundRSV-incidence estimates obtained from routinely-collected healthcare data (e.g., MarketScan) are commonly adjusted for under-reporting using test positivity reported in national Surveillance Systems (NREVSS). However, NREVSS lacks detail on patient-level characteristics and the validity of applying a single positivity estimate across diverse patient groups is uncertain. We aimed to describe testing practices and test positivity across subgroups of private health insurance enrollees in the US and illustrate the possible magnitude of misclassification when using NREVSS to correct for RSV under ascertainment.MethodsUsing billing records, we determined distributions of RSV-test claims and test positivity among a national sample of private insurance enrollees. Tests were considered positive if they coincided with an RSV-diagnosis. We illustrated the influence of positivity variation across sub-populations when accounting for untested acute respiratory infections.ResultsMost tests were for children (age 0–4: 65.8%) and outpatient encounters (78.3%). Test positivity varied across age (0–4: 19.8%, 5–17: 1.8%, adults: 0.7%), regions (7.6–16.1%), settings (inpatient 4.7%, outpatient 14.2%), and test indication (5.0–35.9%). When compared to age, setting or indication-specific positivity, bias due to using NREVSS positivity to correct for untested ARIs ranged from − 76% to 3556%.ConclusionsRSV-test positivity depends on the characteristics of patients for whom those tests were ordered. NREVSS-based correction for RSV-under-ascertainment underestimates the true incidence among children and overestimate rates among adults. Demographic-specific detail on testing practice and positivity can improve the accuracy of RSV-incidence estimates.

Cepheid Xpert Xpress Flu/RSV evaluation performed by minimally trained non-laboratory operators in a CLIA-waived environment

The COVID-19 pandemic highlighted the significance of readily available and easily performed viral testing for surveillance during future infectious pandemics. The objectives of this study were: to assess the performance of the Xpert Xpress Flu and/or RSV test, a multiplex PCR assay for detecting influenza A and B virus and respiratory syncytial virus nucleic acids in respiratory tract specimens, relative to the Quidel Lyra Influenza A+B assay and the Prodesse ProFlu+ assay, and the system's ease of use by minimally trained operators. Overall, the Xpert Xpress Flu/RSV test demonstrated a high positive and negative percent agreement with the comparator assays, and was easy to use and interpret results, based on the operators’ feedback. We concluded that the Xpert Xpress Flu/RSV test is sensitive, specific, and easy to use for the diagnosis of influenza and RSV by minimally trained operators and can be a valuable tool in future infectious clusters or pandemics.

Sensitivity and specificity of surveillance case definitions in detection of influenza and respiratory syncytial virus among hospitalized patients, New Zealand, 2012–2016

BackgroundThe WHO is exploring the value of adding RSV testing to existing influenza surveillance systems to inform RSV control programs. We evaluate the usefulness of four commonly used influenza surveillance case-definitions for influenza and RSV surveillance. MethodsSHIVERS, a multi-institutional collaboration, conducted surveillance for influenza and RSV in four New Zealand hospitals. Nurses reviewed admission logs, enrolled patients with suspected acute respiratory infections (ARI), and obtained nasopharyngeal swabs for RT-PCR. We compared the performance characteristics for identifying laboratory-confirmed influenza and RSV severe acute respiratory infection (SARI), defined as persons admitted with measured or reported fever and cough within 10 days of illness, to three other case definitions: 1. reported fever and cough or shortness of breath, 2. cough and shortness of breath, or 3. cough. ResultsDuring April-September 2012–2016, SHIVERS identified 16,055 admissions with ARI; of 6374 cases consented and tested for influenza or RSV, 5437 (85%) had SARI and 937 (15%) did not. SARI had the highest specificity in detecting influenza (40.6%) and RSV (40.8%) but the lowest sensitivity (influenza 78.8%, RSV 60.3%) among patients of all ages. Cough or shortness of breath had the highest sensitivity (influenza 99.3%, RSV 99.9%) but the lowest specificity (influenza 1.6%, RSV 1.9%). SARI sensitivity among children aged <3 months was 60.8% for influenza and 43.6% for RSV–both lower than in other age groups. ConclusionsWhile SARI had the highest specificity, its sensitivity was limited, especially among children aged <3 months. Cough or shortness of breath was the most sensitive.

1508. Hospitalizations and Emergency Department Visits for Respiratory Syncytial Virus Among Infants Aged &amp;lt; 1 year in the United States: An Analysis of Nationwide Inpatient and Emergency Room Data

BackgroundRespiratory syncytial virus (RSV) is a common cause of illness and hospitalization for infants and children globally. The objective of this study was to characterize the burden of RSV and all-cause bronchiolitis (ACB) inpatient hospitalizations and emergency room department (ED) visits in U.S. infants aged < 1 year with the most recent years of data available.Figure 1. RSV and ACB hospitalizations among US infants <1 year old (NIS 2016) Figure 2. ED visits due to RSV and ACB among US infants < 1 year old (NEDS 2016) MethodsThe National (Nationwide) Inpatient Sample (NIS) and the Nationwide Emergency Department Sample (NEDS), which are large national publicly available all-payer databases in the U.S., were used to estimate the burden of RSV in 2016 based on ICD-9 and 10 codes. The proportions of hospitalizations or ED visits due to RSV in infants aged < 1 year were quantified. Due to the potential of missing RSV encounters based on coding practices, ACB was also evaluated. Based on availability of variables and data recency, 2011 NIS data were used to describe RSV burden by age in months. Sensitivity analyses were conducted with NIS and NEDS data from other years (2011-2015).ResultsA clear seasonal pattern was observed for RSV hospitalizations and RSV ED visits with a peak in December-February and a trough in June-August in 2016. During the RSV season and peak months, RSV was a leading cause of hospitalization (12065/45490=27% in Jan and 12050/45080=27% in Feb) and ED visits (26423/316709=8% in Jan and 24721/306397=8% in Feb)) among U.S. infants under 1 year of age. Similar patterns were seen for ACB in 2016 (38% hospitalization and 17-18% ED visits in Jan and Feb) and for RSV and ACB in the other years. For the inpatient setting in 2011, RSV hospitalizations were the highest among the youngest patients (except those aged <1 month) and decreased with age during the RSV season and peak months.ConclusionThese results show that during the RSV season, RSV and ACB were a leading cause of hospitalization and ED visit among US infants under 1 year of age. Current policy does not support routine RSV testing of clinical lower respiratory tract infections (LRTIs) among infants. In that context, as an approximation of RSV LRTI visits in each setting, ACB can be considered an upper bound and RSV can be considered a lower bound of the true proportion of hospital encounters associated with RSV in these settings..DisclosuresMina Suh, MPH, International Health, EpidStrategies (Employee) Xiaohui Jiang, MS, EpidStrategies (Employee)

A novel point-of-care test of respiratory syncytial viral RNA based on cellulose-based purification and convective PCR

BackgroundRespiratory syncytial virus (RSV) infection is a global public-health problem. Timely diagnostics are needed for high-risk patients. Several methods have been used for RSV detection but not suitable for on-site detection due to the requirement of specialized laboratories and expensive equipment. MethodsWe developed a convenient, rapid and low-cost method of nucleic acids (NA) extraction based on cellulose paper, which could extract NA from nasopharyngeal swabs (NPSs) within 1 min. This extraction method was integrated with fluorescence convection polymerase chain reaction (CPCR), which easily affordable and easy-to-use NA detection of the RSV in 33 min. ResultsThe developed cellulose-based NA purification combine with CPCR (CP-CPCR) reliably detected as little as 0.01 TCID50/mL of RSV cultures. CP-CPCR performance was tested further using NPSs: it showed sensitivity of 100% and a specificity of 100% compared with traditional extraction and amplification methods. ConclusionsOur evaluation confirmed high specificity, sensitivity and efficient of the CP-CPCR, which can be used widely for RSV testing in resource-limited settings.

Evaluation of cobas Influenza A/B & RSV Test for Diagnosis of Equine Influenza

A rapid and sensitive diagnostic method is needed to help prevent the spread of equine influenza virus. The cobas Influenza A/B & RSV test for the cobas Liat system (Roche Diagnostics) is based on real-time reverse transcription polymerase chain reaction and is designed to broadly detect influenza A virus RNA within 20 minutes. It detected a broad range of equine influenza virus strains, and detected equine influenza virus RNA from nasal swabs of infected horses at the same level as real-time reverse transcription polymerase chain reaction, although it returned some invalid results (7.7%). This suggests that cobas Influenza A/B & RSV test is highly sensitive to equine influenza virus, but should be improved to reduce the rate of invalid results.

ASPERGILLOSIS COMPLICATING SEVERE INFLUENZA AND RSV PNEUMONIA IN ICU PATIENTS: A RETROSPECTIVE COHORT STUDY

Background: Invasive pulmonary aspergillosis (IPA) has been recognized as a complication of influenza infection even in immunocompetent patients. We aimed to understand the incidence of IPA as well as other coinfections over multiple seasons in patients with either severe influenza and RSV pneumonia in the intensive care unit (ICU), with a focus on solid organ transplant (SOT). Materials and Methods: A retrospective cohort study was conducted in a single center in Chicago. Data were collected over six seasons (January 2012 – March 2018) from adult patients admitted to the ICU at a large urban tertiary care center with severe RSV or influenza pneumonia. Patients were included if they had a positive RSV or influenza PCR test, older than 18 years, admitted to the ICU with acute respiratory failure. IPA was defined per both the EORTC/MSG criteria as well as the revised AspICU criteria.[1] Statistics were calculated with Stata 16.0 (StataCorp, TX). Results: Overall the incidence of IPA was low in patients with RSV or influenza (5.5% and 1.7%, respectively). Patients diagnosed with IPA were both predominantly of male sex in both RSV (87.5%, n=7) and influenza (83.3%, n=6) groups. The median overall length of stay was significantly longer in both RSV (23.6 +/- 4.3 d) and influenza (24.6 +/- 3.7 d) groups with IPA. Patients with RSV that developed IPA had significant mortality (62.5%, p=0.01), while patients with influenza did not (33.3%, p=0.11). In patients with SOT, IPA developed in 16.7% (n=1) of SOT patients with influenza, and 12.5% (n=1) with RSV. All SOT patients with IPA had a history of liver transplantation with comorbidities (malignancy, post-op complications) and developed bacterial coinfections. In patients with severe RSV, history of hematological malignancy and neutropenia showed trends towards the development of IPA. In contrast, those with influenza had a history of hematological malignancy (p=0.03), hematopoietic stem cell transplant (p=0.01), non-transplant related immunosuppression (p=0.01), and history of solid organ malignancy (p=0.01) as significant factors associated with IPA. Other coinfections were common with incidences of RSV and influenza groups at bacterial (27.1% v 46.7%), viral (6.9% v 11.7%), and non-aspergillosis fungal (1.3% v 13.3%).Conclusions and Discussion: The incidence of IPA was significantly lower in both RSV and influenza groups in our study (5.5% and 1.7%) than previously reported in similar studies. While RSV-infected patients with IPA had significant mortality, influenza-infected patients did not. SOT itself does not seem to be a significant factor contributing to the development of IPA in the setting of severe viral pneumonia. At the same time, malignancy and profound immunosuppression are factors strongly associated with the development of IPA. Other coinfections with bacterial, viral, and fungal pathogens are common in those with both severe RSV and influenza pneumonia. Reference: 1. Schauwvlieghe A, Rijnders BJA, Philips N, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med 2018;6:782-92.

320: Physiologic parameters and sepsis bundle failures during the 2017-2018 influenza season

We characterized gravidas with influenza-like illness during the 2017-2018 influenza season in the context of a hospital-wide sepsis bundle. The bundle is triggered for any 2 abnormal vital signs, defined as: temperature < 36°C or ≥38°C, heart rate >90/min, systolic blood pressure < 90mmHg, and respiratory rate >20/min. This was a retrospective cohort study of 2017-2018 encounters for influenza-like illness (ILI), defined as respiratory symptoms for which a rapid flu test was ordered. Multiple encounters during a single pregnancy were possible. We excluded patients with RSV, pyelonephritis, non-influenza indications, or indeterminate flu testing. We compared “abnormal” vital signs recorded within 4h of presentation and hospitalization rates among gravidas with positive versus negative flu tests. Missing values were assumed normal. Between September 1, 2017 and March 31, 2018, 913 encounters for ILI were identified. Of these, 100(11%) were excluded (Figure 1). Of the 165 first, 271 second, and 377 third trimester encounters, 64(39%), 85(31%), and 144(38%) were influenza-positive, respectively (Table 1). Influenza positivity was associated with “abnormal” vital signs in all trimesters. Influenza-positive gravidas had two to three times the risk of having 2 abnormal vital signs, which would trigger sepsis bundle initiation and assessment for end-organ damage (i.e., lactate). Relative to influenza-negative encounters, influenza-positivity was associated with 1.6 to 2.1 times the risk for hospital admission for all trimesters, though absolute frequency of admission was low: 36%, 44%, and 58% for each trimester. ICU admission was rare. Influenza-positivity in pregnancy is associated with vitals signs that trigger a sepsis alert requiring further action, regardless of trimester. Despite higher risk for hospital admission among gravidas with influenza, most women are actually discharged after evaluation. A hospital-wide sepsis bundle fails to identify pregnant women with influenza at highest risk for severe morbidity.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Estimated Burden of Community-Onset Respiratory Syncytial Virus-Associated Hospitalizations Among Children Aged

BackgroundRespiratory syncytial virus (RSV) is a major cause of hospitalizations in young children. We estimated the burden of community-onset RSV-associated hospitalizations among US children aged <2 years by extrapolating rates of RSV-confirmed hospitalizations in 4 surveillance states and using probabilistic multipliers to adjust for ascertainment biases.MethodsFrom October 2014 through April 2015, clinician-ordered RSV tests identified laboratory-confirmed RSV hospitalizations among children aged <2 years at 4 influenza hospitalization surveillance network sites. Surveillance populations were used to estimate age-specific rates of RSV-associated hospitalization, after adjusting for detection probabilities. We extrapolated these rates using US census data.ResultsWe identified 1554 RSV-associated hospitalizations in children aged <2 years. Of these, 27% were admitted to an intensive care unit, 6% needed mechanical ventilation, and 5 died. Most cases (1047/1554; 67%) had no underlying condition. Adjusted age-specific RSV hospitalization rates per 100 000 population were 1970 (95% confidence interval [CI],1787 to 2177), 897 (95% CI, 761 to 1073), 531 (95% CI, 459 to 624), and 358 (95% CI, 317 to 405) for ages 0–2, 3–5, 6–11, and 12–23 months, respectively. Extrapolating to the US population, an estimated 49 509–59 867 community-onset RSV-associated hospitalizations among children aged <2 years occurred during the 2014–2015 season.ConclusionsOur findings highlight the importance of RSV as a cause of hospitalization, especially among children aged <2 months. Our approach to estimating RSV-related hospitalizations could be used to provide a US baseline for assessing the impact of future interventions.

2620. Respiratory Syncytial Virus Rapid Antigen Detection Test, Can It Be Trusted?

BackgroundMany emergency departments and urgent care settings use the commonly available Respiratory Syncytial Virus Rapid Antigen Detection Test (RSV RADT) to diagnose children with RSV. We noted discordant results between RADT and definitive testing. Our study looked at the positive predictive value (PPV) and the false discovery rate (FDR) of the RSV RADT at our facility.MethodsWe pro- and retrospectively reviewed all patients with positive RSV RAPD tests from July 1, 2017 through March 31, 2019. The test utilized was the QuickVue® RSV Test Kit (QUIDEL Corp, CA, USA), which detects the viral fusion protein present in RSV. Of the tests performed, we chose patients who had definitive testing with either a direct fluorescent antibody (DFA) or a polymerase chain reaction (PCR). We then calculated the PPV as well as the FDR of the RSV RADT during the total interval period, as well as off-season periods (April 1 through October 31) and in-season periods (November 1 through March 31).ResultsDuring the study period there were 1128 RSV RADT tests performed, of which 232 had definitive testing with either DFA or PCR (Figures 1 and 2). We found the overall PPV during the study period was 63.3%. During the off-season 30 positive RSV RADT received definitive testing, of which 6 were positive, which yields a PPV of only 20%. In season, 202 RSV RADT received additional testing with 141 positive for RSV. The PPV was 69.8%. The FDR correlated with 36.7% throughout the entire studied period, 80% during the off-season and 30.2% during in-season. As expected, the PPV was higher during times of higher prevalence (Figure 3).ConclusionBased on our results, utilization of the RSV RADT during time of low prevalence yields a high false detection rate and should therefore be discouraged. The use during times of high prevalence yields only modest results and is unlikely to aid in clinical decision-making. Our results differ from those published by the manufacturer (PPV 84%), and may reflect differences in sample collection in the acute care setting. Disclosures All authors: No reported disclosures.

901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants

BackgroundRSV is the principal cause of lower respiratory tract infection (LRTI) among infants, and a significant unmet need exists for RSV prevention in healthy infants. We have developed a highly potent, extended half-life monoclonal antibody (mAb), to protect infants for an entire RSV season using a single IM dose. Here we report the efficacy, safety, pharmacokinetics, and anti-drug antibody (ADA) responses for MEDI8897 in palivizumab-ineligible preterm infants born between 29 and 35 weeks gestation.MethodsA total of 1,453 Infants were randomized 2:1 to receive a single 50 mg IM injection of MEDI8897 (n = 969) or placebo (n = 484) and followed for 360 days. Enrollment occurred just prior to the 2016 and 2017 RSV seasons in 23 northern and southern hemisphere countries. Blood was collected periodically. Infants with a medically attended (MA) LRTI (outpatient or inpatient) had nasal swabs obtained for central RSV testing by RT-PCR. Predefined clinical criteria were used for the case definition.ResultsA total of 1,417 (97.5%) subjects completed the 150-day efficacy follow-up period and 1,367 (94.1%) completed the study. In the MEDI8897 group, a 70.1% (95% CI: 52.3%, 81.2%; P < 0.0001) reduction in the incidence of medically attended RSV LRTI and a 78.4% (95% CI: 51.9%, 90.3%; P = 0.0002) reduction in the incidence of RSV LRTI hospitalization was achieved. These efficacy results were consistent when analyzed by hemisphere, RSV subtype, and subject demographics. Similar proportions of adverse events (86.8% placebo; 86.2% MEDI8897) and serious adverse events (16.9% placebo; 11.2% MEDI8897) were reported in study subjects. There were no significant hypersensitivity reactions with similar proportions reported for both groups (0.6% placebo; 0.5% MEDI8897). The incidence of ADA detected any time post baseline was low (3.8% placebo; 5.6% MEDI8897) with no impact on PK or safety. The occurrence of non-RSV LRTIs was similar for both groups indicating no replacement by other pathogens.ConclusionIn this large randomized study of RSV prophylaxis in healthy preterm infants, MEDI8897 immunoprophylaxis provided a significant reduction in RSV MA-LRTI and hospitalization. These results have promising implications for the future of RSV prophylaxis for all infants.This study was funded by AstraZeneca and sanofi pasteur.Disclosures All Authors: No reported Disclosures.