Psychometric evaluation of the respiratory syncytial virus infection, intensity and impact questionnaire (RSV-iiiQ) in adults.

BACKGROUND: Despite a number of respiratory syncytial virus (RSV) vaccine candidates being tested in clinical trials, disease-specific, self-reported instruments assessing symptom severity of RSV infection from the perspective of adult patients are still needed. The RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ) was adapted from the Influenza Intensity and Impact Questionnaire (FluiiQ™). This study evaluated some measurement properties of the RSV-iiiQ. METHODS: Data were collected in a web-based survey over two consecutive days. Participants completed the RSV-iiiQ, the Patient Global Impression of Severity, Sheehan Disability Scale, Patient Global Impression of Change, EQ-5D-5L, and a demographic questionnaire. Test-retest reliability, internal consistency, construct validity, and responsiveness of the RSV-iiiQ scales were assessed. RESULTS: 111 adults with RSV were enrolled and self-reported a variety of symptoms across the range of disease severity via a web-based platform. The RSV-iiiQ scales demonstrated satisfactory test-retest reliability, construct validity, and discriminating ability. One-factor confirmatory factor analyses confirmed that each of the four scales was sufficiently unidimensional, and internal consistencies indicated that the computation of RSV-iiiQ scale scores was plausible. Correlation-based analyses provided support for the construct validity of the RSV-iiiQ scores, and known groups analyses supported discriminating ability. Estimates of responsiveness of the scale scores were also satisfactory. CONCLUSIONS: RSV infection is highly symptomatic and causes significant disease burden, and self-report instruments assessing symptom severity and impact are important for evaluation of new treatments. This study describes the preliminary psychometric properties of the RSV-iiiQ and indicates this tool may be useful for the assessment of the severity of symptoms and impact of acute RSV infection in adults. The findings also indicated two items, Runny nose and Ear pain, may be unnecessary and should be revisited using item response theory analysis with a larger sample size.

Association of SARS-CoV-2 status and antibiotic-resistant bacteria with inadequate empiric therapy in hospitalized patients: a US multicenter cohort evaluation (July 2019 - October 2021).

BACKGROUND: Antibiotic usage and antibiotic resistance (ABR) patterns changed during the COVID-19 pandemic. Inadequate empiric antibiotic therapy (IET) is a significant public health problem and contributes to ABR. We evaluated factors associated with IET before and during the COVID-19 pandemic to determine the impact of the pandemic on antibiotic management. METHODS: This multicenter, retrospective cohort analysis included hospitalized US adults who had a positive bacterial culture (specified gram-positive or gram-negative bacteria) from July 2019 to October 2021 in the BD Insights Research Database. IET was defined as antibacterial therapy within 48 h that was not active against the bacteria. ABR results were based on susceptibility testing and reports from local facilities. Multivariate analysis was used to identify risk factors associated with IET in patients with any positive bacterial culture and ABR-positive cultures, including multidrug-resistant (MDR) bacteria. RESULTS: Of 278,344 eligible patients in 269 hospitals, 56,733 (20.4%) received IET; rates were higher in patients with ABR-positive (n = 93,252) or MDR-positive (n = 39,000) cultures (34.9% and 45.0%, respectively). Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients had significantly higher rates of IET (25.9%) compared with SARS-CoV-2-negative (20.3%) or not tested (19.7%) patients overall and in the ABR and MDR subgroups. Patients with ABR- or MDR-positive cultures had more days of therapy and longer lengths of stay. In multivariate analyses, ABR, MDR, SARS-CoV-2-positive status, respiratory source, and prior admissions were identified as key IET risk factors. CONCLUSIONS: IET remained a persistent problem during the COVID-19 pandemic and occurred at higher rates in patients with ABR/MDR bacteria or a co-SARS-CoV-2 infection.

Healthcare-Associated Respiratory Syncytial Virus in Children's Hospitals.

BACKGROUND: Outbreaks of healthcare-associated respiratory syncytial virus (HA-RSV) infections in children are well described, but less is known about sporadic HA-RSV infections. We assessed the epidemiology and clinical outcomes associated with sporadic HA-RSV infections. METHODS: We retrospectively identified hospitalized children ≤18 years old with HA-RSV infections in six children's hospitals in the United States during the respiratory viral seasons October-April in 2016-2017, 2017-2018, and 2018-2019 and prospectively from October 2020 through November 2021. We evaluated outcomes temporally associated with HA-RSV infections including escalation of respiratory support, transfer to the pediatric intensive care unit (PICU), and in-hospital mortality. We assessed demographic characteristics and comorbid conditions associated with escalation of respiratory support. RESULTS: We identified 122 children (median age 16.0 months [IQR 6, 60 months]) with HA-RSV. The median onset of HA-RSV infections was hospital day 14 (IQR 7, 34 days). Overall, 78 (63.9%) children had two or more comorbid conditions; cardiovascular, gastrointestinal, neurologic/neuromuscular, respiratory, and premature/ neonatal comorbidities were most common. Fifty-five (45.1%) children required escalation of respiratory support and 18 (14.8%) were transferred to the PICU. Five (4.1%) died during hospitalization. In the multivariable analysis, respiratory comorbidities (aOR: 3.36 [CI95 1.41, 8.01]) were associated with increased odds of escalation of respiratory support. CONCLUSIONS: HA-RSV infections cause preventable morbidity and increase healthcare resource utilization. Further study of effective mitigation strategies for HA-respiratory viral infections should be prioritized; this priority is further supported by the impact of the COVID-19 pandemic on seasonal viral infections.

Assessing the patient experience of respiratory syncytial virus infection: development of a patient-reported outcome measure.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in older adults. Despite a number of RSV vaccine candidates in clinical trials, there are no existing disease-specific, self-reported measures that assess the symptoms and severity of RSV infection from the perspective of adult patients with acute RSV. The objective of this study was to describe the initial conceptualization and development of the RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ), a new patient-reported outcome measure. METHODS: A targeted review of the literature identified relevant existing measures, symptoms, and impacts of RSV. A draft version of the RSV-iiiQ was developed based on the Influenza Intensity and Impact Questionnaire (Flu-iiQ) with expert input. Qualitative interviews (N = 20) were conducted with participants to optimize the RSV-iiiQ conceptual model and confirm the content validity of the RSV-iiiQ. Interviews included concept elicitation and a cognitive debriefing assessment. A draft conceptual framework was developed, and the electronic clinical outcome assessment was piloted. All steps of instrument development followed Food and Drug Administration guidance for patient-reported outcomes. RESULTS: In-depth concept elicitation interviews followed by cognitive debriefings demonstrated that the content of the items was comprehensive, covered the breadth of RSV symptoms and impacts, and was relevant to the experiences of individuals with RSV. Both the paper and electronic versions of the RSV-iiiQ were easily completed. Minor refinements were made to some items based on participant feedback, and the draft conceptual framework was refined. CONCLUSIONS: The RSV-iiiQ was developed for use in clinical trials to measure the symptom intensity and impact of acute RSV infection from the perspective of adult patients. The tool was developed in accordance with current regulatory guidance and is useful to support patient-focused drug development.

Morbidity and mortality of hospitalised patients with candidemia during the various severe acute respiratory syndrome coronavirus 2 pandemic waves: A multicentre evaluation of 248 US hospitals.

BACKGROUND: Studies evaluating outcomes of COVID-19 patients with candidemia are limited and have only evaluated a single timepoint during the pandemic. OBJECTIVES: To compare the prevalence and outcomes associated with candidemia in patients based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status and through the various pandemic waves (1 March 2020-5 March 2022). PATIENTS/METHODS: Multicentre, retrospective cohort analysis of data from 248 US medical facilities using the BD Insights Research Database (Becton, Dickinson and Company, Franklin Lakes, New Jersey, USA). Eligible patients were adults aged ≥18 years who were hospitalised for >1 day, had a SARS-CoV-2 test and a positive blood culture for Candida spp. RESULTS: During the study time frame, there were 2,402,879 hospital admissions; 234,903 (9.7%) and 2,167,976 (90.3%) patients were SARS-CoV-2 positive and negative, respectively. A significantly higher rate of candidemia/1000 admissions was observed in SARS-CoV-2-positive patients compared to SARS-CoV-2-negative patients (3.18 vs. 0.99; p < .001). The highest candidemia rate for SARS-CoV-2-positive patients was observed during the Alpha SARS-CoV-2 wave (June 2020-August 2020) with the lowest candidemia rate during the Omicron wave. Hospital mortality was significantly higher in SARS-CoV-2-positive patients compared to SARS-CoV-2-negative patients with candidemia (59.6% vs. 30.8%; p < .001). When evaluating the mortality rate through the various pandemic waves, the rate for the overall population did not change. CONCLUSIONS: Our study indicates high morbidity and mortality for hospitalised patients with COVID-19 and candidemia which was consistent throughout the pandemic. Patients with COVID-19 are at an increased risk for candidemia; importantly, the magnitude of which may differ based on the circulating variant.

Real-Time Monitoring of Infectious Disease Outbreaks with a Combination of Google Trends Search Results and the Moving Epidemic Method: A Respiratory Syncytial Virus Case Study.

The COVID-19 pandemic has disrupted the seasonal patterns of several infectious diseases. Understanding when and where an outbreak may occur is vital for public health planning and response. We usually rely on well-functioning surveillance systems to monitor epidemic outbreaks. However, not all countries have a well-functioning surveillance system in place, or at least not for the pathogen in question. We utilized Google Trends search results for RSV-related keywords to identify outbreaks. We evaluated the strength of the Pearson correlation coefficient between clinical surveillance data and online search data and applied the Moving Epidemic Method (MEM) to identify country-specific epidemic thresholds. Additionally, we established pseudo-RSV surveillance systems, enabling internal stakeholders to obtain insights on the speed and risk of any emerging RSV outbreaks in countries with imprecise disease surveillance systems but with Google Trends data. Strong correlations between RSV clinical surveillance data and Google Trends search results from several countries were observed. In monitoring an upcoming RSV outbreak with MEM, data collected from both systems yielded similar estimates of country-specific epidemic thresholds, starting time, and duration. We demonstrate in this study the potential of monitoring disease outbreaks in real time and complement classical disease surveillance systems by leveraging online search data.

Clinical impact of healthcare-associated respiratory syncytial virus in hospitalized adults.

OBJECTIVE: To describe the clinical impact of healthcare-associated (HA) respiratory syncytial virus (RSV) in hospitalized adults. DESIGN: Retrospective cohort study within a prospective, population-based, surveillance study of RSV-infected hospitalized adults during 3 respiratory seasons: October 2017-April 2018, October 2018-April 2019, and October 2019-March 2020. SETTING: The study was conducted in 2 academically affiliated medical centers. PATIENTS: Each HA-RSV patient (in whom RSV was detected by PCR test ≥4 days after hospital admission) was matched (age, sex, season) with 2 community-onset (CO) RSV patients (in whom RSV was detected ≤3 days of admission). METHODS: Risk factors and outcomes were compared among HA-RSV versus CO-RSV patients using conditional logistic regression. Escalation of respiratory support associated with RSV detection (day 0) from day -2 to day +4 was explored among HA-RSV patients. RESULTS: In total, 84 HA-RSV patients were matched to 160 CO-RSV patients. In HA-RSV patients, chronic kidney disease was more common, while chronic respiratory conditions and obesity were less common. HA-RSV patients were not more likely to be admitted to an ICU or require mechanical ventilation, but they more often required a higher level of care at discharge compared with CO-RSV patients (44% vs 14%, respectively). Also, 29% of evaluable HA-RSV patients required respiratory support escalation; these patients were older and more likely to have respiratory comorbidities, to have been admitted to intensive care, and to die during hospitalization. CONCLUSIONS: HA-RSV in adults may be associated with escalation in respiratory support and an increased level of support in living situation at discharge. Infection prevention and control strategies and RSV vaccination of high-risk adults could mitigate the risk of HA-RSV.

A Multicenter Comparison of Prevalence and Predictors of Antimicrobial Resistance in Hospitalized Patients Before and During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

Background: Antibacterial therapy is frequently used in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without evidence of bacterial infection, prompting concerns about increased antimicrobial resistance (AMR). We evaluated trends in AMR before and during the SARS-CoV-2 pandemic. Methods: This multicenter, retrospective cohort analysis included hospitalized adults aged ≥18 years with >1-day inpatient admission and a record of discharge or death from 271 US facilities in the BD Insights Research Database. We evaluated rates of AMR events, defined as positive cultures for select gram-negative and gram-positive pathogens from any source, with nonsusceptibility reported by commercial panels before (1 July 2019-29 February 2020) and during (1 March 2020-30 October 2021) the SARS-CoV-2 pandemic. Results: Of 5 518 666 admissions evaluated, AMR rates per 1000 admissions were 35.4 for the prepandemic period and 34.7 for the pandemic period (P ≤ .0001). In the pandemic period, AMR rates per 1000 admissions were 49.2 for SARS-CoV-2-positive admissions, 41.1 for SARS-CoV-2-negative admissions, and 25.7 for patients untested (P ≤ .0001). AMR rates per 1000 admissions among community-onset infections during the pandemic were lower versus prepandemic levels (26.1 vs 27.6; P < .0001), whereas AMR rates for hospital-onset infections were higher (8.6 vs 7.7; P < .0001), driven largely by SARS-CoV-2-positive admissions (21.8). AMR rates were associated with overall antimicrobial use, rates of positive cultures, and higher use of inadequate empiric therapy. Conclusions: Although overall AMR rates did not substantially increase from prepandemic levels, patients tested for SARS-CoV-2 infection had a significantly higher rate of AMR and hospital-onset infections. Antimicrobial and diagnostic stewardship is key to identifying this high-risk AMR population.

Epidemiology and outcomes of culture-positive bloodstream pathogens prior to and during the SARS-CoV-2 pandemic: a multicenter evaluation.

BACKGROUND: Bloodstream infections (BSIs) are an important cause of morbidity and mortality in hospitalized patients. We evaluate incidence of community- and hospital-onset BSI rates and outcomes before and during the SARS-CoV-2 pandemic. METHODS: We conducted a retrospective cohort study evaluating patients who were hospitalized for ≥ 1 day with discharge or death between June 1, 2019, and September 4, 2021, across 271 US health care facilities. Community- and hospital-onset BSI and related outcomes before and during the SARS-CoV-2 pandemic, including intensive care admission rates, and overall and ICU-specific length of stay (LOS) was evaluated. Bivariate correlations were calculated between the pre-pandemic and pandemic periods overall and by SARS-CoV-2 testing status. RESULTS: Of 5,239,692 patient admissions, there were 20,113 community-onset BSIs before the pandemic (11.2/1000 admissions) and 39,740 (11.5/1000 admissions) during the pandemic (P ≤ 0.0062). Corresponding rates of hospital-onset BSI were 2,771 (1.6/1000 admissions) and 6,864 (2.0/1000 admissions; P < 0.0062). Compared to the pre-pandemic period, rates of community-onset BSI were higher in patients who tested negative for SARS-CoV-2 (15.8/1000 admissions), compared with 9.6/1000 BSI admissions among SARS-CoV-2-positive patients. Compared with patients in the pre-pandemic period, SARS-CoV-2-positive patients with community-onset BSI experienced greater ICU admission rates (36.6% vs 32.8%; P < 0.01), greater ventilator use (10.7% vs 4.7%; P < 0.001), and longer LOS (12.2 d vs 9.1 d; P < 0.001). Rates of hospital-onset BSI were higher in the pandemic vs the pre-pandemic period (2.0 vs 1.5/1000; P < 0.001), with rates as high a 7.3/1000 admissions among SARS-CoV-2-positive patients. Compared to the pre-pandemic period, SARS-CoV-2-positive patients with hospital-onset BSI had higher rates of ICU admission (72.9% vs 55.4%; P < 0.001), LOS (34.8 d vs 25.5 d; P < 0.001), and ventilator use (52.9% vs 21.5%; P < 0.001). Enterococcus species, Staphylococcus aureus, Klebsiella pneumoniae, and Candida albicans were more frequently detected in the pandemic period. CONCLUSIONS AND RELEVANCE: This nationally representative study found an increased risk of both community-onset and hospital-onset BSI during the SARS-CoV-2 pandemic period, with the largest increased risk in hospital-onset BSI among SARS-CoV-2-positive patients. SARS-CoV-2 positivity was associated with worse outcomes.

The clinical impact of multiple prevention strategies for respiratory syncytial virus infections in infants and high-risk toddlers in the United States.

BACKGROUND: Respiratory syncytial virus (RSV) remains a leading cause of medically-attended acute respiratory infection in infants and children. With multiple preventative interventions under development, accurate estimates of health care resource utilization are essential for policy decision making. METHODS: We developed a literature-based decision-tree model that estimated annual medically-attended RSV (MA-RSV) lower respiratory tract infection (LRTI) and non-LRTI episodes in the US for all infants and for high-risk toddlers. The model accounted for the gestational age and birth-month of infants, and the seasonal variation in RSV incidence. The impact of no prophylaxis, palivizumab, maternal vaccine, and long-acting monoclonal antibody (mAb) interventions was estimated. RESULTS: We estimated 1.23 million (range: 0.96 million-1.40 million) annual MA-RSV LRTI/non-LRTI episodes comprised of 1.19 million (range: 0.93 million-1.36 million) emergency department (ED) and outpatient visits, and 39,040 (range: 32,726-45,851) hospitalizations. Outpatient and ED visits were comprised of 586,034 (range: 430,595-718,868) LRTIs and 608,733 (range: 495,705-644,658) non-LRTIs. The long-acting mAb intervention resulted in the greatest number of averted outpatient and ED episodes (310,997 [53%] LRTIs; 284,305 [47%] non-LRTIs) and hospitalizations (21,845 [56%]). Full-term infants constitute the highest proportion of episodes across all interventions. CONCLUSIONS: MA-RSV disease is substantial in infants and high-risk toddlers. Long-acting mAbs are most effective at reducing the number of MA-RSV LRTI/non-LRTI episodes, and the only intervention that prevents disease in older infants (≥6 months old).

Change in functional status associated with respiratory syncytial virus infection in hospitalized older adults.

BACKGROUND: Respiratory syncytial virus (RSV) causes severe respiratory illnesses in infants and older adults. Older adults are frequently hospitalized with RSV illness and may experience loss of function. This study evaluated longitudinal changes in function associated with RSV hospitalization in older adults. METHODS: Adults ≥60 years hospitalized with laboratory-confirmed RSV were enrolled (N = 302). Demographics and comorbidities were collected. Functional status was assessed 2 weeks pre-hospitalization by recall, at enrollment, hospital discharge and 2, 4, and 6 months post-discharge using the Lawton-Brody Instrumental Activities of Daily Living (IADL) (scale 0-8) and Barthel ADL Index (scale 0-100). RESULTS: RSV-associated hospitalization resulted in acute functional loss. Median IADL (5 vs. 3, p < 0.0001) and ADL (90 vs. 70, p < 0.0001) scores decreased significantly from pre-hospitalization to admission and remained decreased at discharge. There were no statistically significant differences between pre-hospitalization and 2-, 4-, or 6-month scores. However, 33% and 32% of subjects experienced decreased 6-month IADL and ADL scores, respectively. Additionally, 14% required a higher level of care at discharge. When stratified by pre-hospitalization living situation, 6-month IADL scores declined significantly for those admitted from a skilled nursing facility (3 vs. 1, p = 0.001). In multivariate analysis, male sex and diabetes were associated with a 6-month decline in ADL score of ≥10. CONCLUSIONS: Older adults hospitalized with RSV demonstrate acute functional decline that may become prolonged. Pre-hospitalization living situation may predict patient outcomes. Further study is needed with hospitalized age-matched controls and refined measurement tools to better define the specific impact of RSV on function.

Bacteremia in Adults Admitted from the Emergency Department with Laboratory-Confirmed Respiratory Syncytial Virus.

BACKGROUND: Collecting blood cultures from patients admitted from the emergency department (ED) with acute respiratory infection (ARI) is common, but the rate of secondary bacteremia in adult patients admitted from the ED with ARI associated with respiratory syncytial virus (RSV) is unknown. Indiscriminate collection of blood cultures can be associated with contaminated blood cultures and increased inappropriate antimicrobial use and health care costs. OBJECTIVE: This study sought to determine the rate and etiology of secondary bacteremia, factors associated with secondary bacteremia, and factors associated with collecting blood cultures in the ED, in adults hospitalized with RSV. METHODS: We performed a retrospective substudy using data from a prospective study of adults admitted with RSV infections during two respiratory seasons (October 2017 to April 2018 and October 2018 to April 2019). Blood cultures were collected at the discretion of ED providers. We compared demographic and clinical characteristics among those with and without secondary bacteremia and among those with and without blood cultures collected using multivariate logistic regression models. RESULTS: Of the 365 hospitalized RSV-positive patients (mean age 68.8 years), 269 (73.7%) had blood cultures collected in the ED and 18 (6.7%) patients had secondary bacteremia, most commonly from a nonrespiratory source (n = 13). Patients with asthma and chronic obstructive pulmonary disease were significantly less likely to have secondary bacteremia. Patients who were immunocompromised, met systemic inflammatory response syndrome criteria, or had pneumonia described on chest x-ray reports were more likely to have blood cultures collected. CONCLUSIONS: Overall, 6.7% of adults hospitalized with RSV infections had secondary bacteremia, more commonly from nonrespiratory sources.

Cost determinants among adults hospitalized with respiratory syncytial virus in the United States, 2017-2019.

BACKGROUND: Respiratory syncytial virus (RSV) infections are common in adults, but data describing the cost of RSV-associated hospitalization are lacking due to inconsistency in diagnostic coding and incomplete case ascertainment. We evaluated costs of RSV-associated hospitalization in adult patients with laboratory-confirmed, community-onset RSV. METHODS: We included adults ≥ 18 years of age admitted to three hospital systems in New York during two RSV seasons who were RSV-positive by polymerase chain reaction (PCR) and had more than or equal to two acute respiratory infection symptoms or exacerbation of underlying cardiopulmonary disease. We abstracted costs from hospital finance systems or converted hospital charges to cost using cost-charge ratios. We converted cost into 2020 US dollars and extrapolated to the United States. We used a generalized linear model to determine predictors of hospitalization cost, stratified by admission to intensive care units (ICU). RESULTS: Cost data were available for 79% (601/756) of eligible patients. The mean total cost of hospitalization was $8403 (CI95 $7240-$9741). The highest costs were those attributed to ICU services $7885 (CI95 $5877-$10,240), whereas the lowest were radiology $324 (CI95 $275-$376). Other than longer length of stay, predictors of higher cost included having chronic liver disease (odds ratio [OR] 1.38 [CI95 1.05-1.80]) for patients without ICU admission and antibiotic use (OR 1.49 [CI95 1.10-2.03]) for patients with ICU admission. The annual US cost was estimated to be $1.2 (CI95 0.9-1.4) billion. CONCLUSION: The economic burden of RSV hospitalization of adults ≥ 18 years of age in the United States is substantial. RSV vaccine programs may be useful in reducing this economic burden.

Severe Clinical Outcomes Among Adults Hospitalized With Respiratory Syncytial Virus Infections, New York City, 2017-2019.

OBJECTIVES: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. We assessed severe clinical outcomes among hospitalized adults that were associated with RSV infections. METHODS: We performed a nested retrospective study in 3 New York City hospitals during 2 respiratory viral seasons, October 2017-April 2018 and October 2018-April 2019, to determine the proportion of patients with laboratory-confirmed RSV infection who experienced severe outcomes defined as intensive care unit (ICU) admission, mechanical ventilation, and/or death. We assessed factors associated with these severe outcomes and explored the effect of RSV-associated hospitalizations on changes in the living situations of surviving patients. RESULTS: Of the 403 patients studied (median age, 69 years), 119 (29.5%) were aged ≥80. Severe outcomes occurred in 19.1% of patients, including ICU admissions (16.4%), mechanical ventilation (12.4%), and/or death (6.7%). Patients admitted from residential living facilities had a 4.43 times higher likelihood of severe RSV infection compared with patients who were living in the community with or without assistance from family or home health aides. At discharge, 56 (15.1%) patients required a higher level of care than at admission. CONCLUSIONS: RSV infection was associated with severe outcomes in adults. Living in a residential facility at admission was a risk factor for severe outcomes and could be a proxy for frailty rather than an independent risk factor. Our data support the development of prevention strategies for RSV infection in older populations, especially older adults living in residential living facilities.

Incidence of Respiratory Syncytial Virus Infection Among Hospitalized Adults, 2017-2020.

BACKGROUND: Respiratory syncytial virus (RSV) causes acute respiratory illness (ARI) and triggers exacerbations of cardiopulmonary disease. Estimates of incidence in hospitalized adults range widely, with few data on incidence in adults with comorbidities that increase the risk of severity. We conducted a prospective, population-based, surveillance study to estimate incidence of RSV hospitalization among adults overall and those with specific comorbidities. METHODS: Hospitalized adults aged ≥18 years residing in the surveillance area with ≥2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened during the 2017-2018, 2018-2019, and 2019-2020 RSV seasons in 3 hospitals in Rochester, New York and New York City. Respiratory specimens were tested for RSV using polymerase chain reaction assays. RSV incidence per 100 000 was adjusted by market share. RESULTS: Active and passive surveillance identified 1099 adults hospitalized with RSV. Annual incidence during 3 seasons ranged from 44.2 to 58.9/100 000. Age-group-specific incidence ranged from 7.7 to 11.9/100 000, 33.5 to 57.5/100 000, and 136.9 to 255.6/100 000 in patients ages 18-49, 50-64, and ≥65 years, respectively. Incidence rates in patients with chronic obstructive pulmonary disease, coronary artery disease, and congestive heart failure were 3-13, 4-7, and 4-33 times, respectively, the incidence in patients without these conditions. CONCLUSIONS: We found a high burden of RSV hospitalization in this large prospective study. Notable was the high incidence among older patients and those with cardiac conditions. These data confirm the need for effective vaccines to prevent RSV infection in older and vulnerable adults.

Effect of Inadequate Empiric Antibacterial Therapy on Hospital Outcomes in SARS-CoV-2-Positive and -Negative US Patients With a Positive Bacterial Culture: A Multicenter Evaluation From March to November 2020.

BACKGROUND: Increased utilization of antimicrobial therapy has been observed during the coronavirus disease 2019 pandemic. We evaluated hospital outcomes based on the adequacy of antibacterial therapy for bacterial pathogens in US patients. METHODS: This multicenter retrospective study included patients with ≥24 hours of inpatient admission, ≥24 hours of antibiotic therapy, and discharge/death from March to November 2020 at 201 US hospitals in the BD Insights Research Database. Included patients had a test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a positive bacterial culture (gram-positive or gram-negative). We used generalized linear mixed models to evaluate the impact of inadequate empiric therapy (IET), defined as therapy not active against the identified bacteria or no antimicrobial therapy in the 48 hours following culture, on in-hospital mortality and hospital and intensive care unit length of stay (LOS). RESULTS: Of 438 888 SARS-CoV-2-tested patients, 39 203 (8.9%) had positive bacterial cultures. Among patients with positive cultures, 9.4% were SARS-CoV-2 positive, 74.4% had a gram-negative pathogen, 25.6% had a gram-positive pathogen, and 44.1% received IET for the bacterial infection. The odds of mortality were 21% higher for IET (odds ratio [OR], 1.21; 95% CI, 1.10-1.33; P < .001) compared with adequate empiric therapy. IET was also associated with increased hospital LOS (LOS, 16.1 days; 95% CI, 15.5-16.7 days; vs LOS, 14.5 days; 95% CI, 13.9-15.1 days; P < .001). Both mortality and hospital LOS findings remained consistent for SARS-CoV-2-positive and -negative patients. CONCLUSIONS: Bacterial pathogens continue to play an important role in hospital outcomes during the pandemic. Adequate and timely therapeutic management may help ensure better outcomes.

Mortality Among US Patients Hospitalized With SARS-CoV-2 Infection in 2020.

Importance: Mortality is an important measure of the severity of a pandemic. This study aimed to understand how mortality by age of hospitalized patients who were tested for SARS-CoV-2 has changed over time. Objective: To evaluate trends in in-hospital mortality among patients who tested positive for SARS-CoV-2. Design, Setting, and Participants: This retrospective cohort study included patients who were hospitalized for at least 1 day at 1 of 209 US acute care hospitals of variable size, in urban and rural areas, between March 1 and November 21, 2020. Eligible patients had a SARS-CoV-2 polymerase chain reaction (PCR) or antigen test within 7 days of admission or during hospitalization, and a record of discharge or in-hospital death. Exposure: SARS-CoV-2 positivity. Main Outcomes and Measures: SARS-CoV-2 infection was defined as a positive SARS-CoV-2 PCR or antigen test within 7 days before admission or during hospitalization. Mortality was extracted from electronically available data. Results: Among 503 409 admitted patients, 42 604 (8.5%) had SARS-CoV-2-positive tests. Of those with SARS-CoV-2-positive tests, 21 592 (50.7%) were male patients. Hospital admissions among patients with SARS-CoV-2-positive tests were highest in the group aged 65 years or older (19 929 [46.8%]), followed by those aged 50 to 64 years (11 602 [27.2%]) and 18 to 49 years (10 619 [24.9%]). Hospital admissions among patients 18 to 49 years of age increased from 1099 of 5319 (20.7%) in April to 1266 of 4184 (30.3%) in June and 2156 of 7280 (29.6%) in July, briefly exceeding those in the group 50 to 64 years of age (June: 1194 of 4184 [28.5%]; 2039 of 7280 [28.0%]). Patients with SARS-CoV-2-positive tests had higher in-hospital mortality than patients with SARS-CoV-2-negative tests (4705 [11.0%] vs 11 707 of 460 805 [2.5%]; P < .001). In-hospital mortality rates increased with increasing age for both patients with SARS-CoV-2-negative tests and SARS-CoV-2-positive tests. In patients with SARS-CoV-2-negative tests, mortality increased from 45 of 11 255 (0.4%) in those younger than 18 years to 4812 of 107 394 (4.5%) in those older than 75 years. In patients with SARS-CoV-2-positive tests, mortality increased from 1 of 454 (0.2%) of those younger than 18 years to 2149 of 10 287 (20.9%) in those older than 75 years. In-hospital mortality rates among patients with SARS-CoV-2-negative tests were similar for male and female patients (6273 of 209 086 [3.0%] vs 5538 of 251 719 [2.2%]) but higher mortality was observed among male patients with SARS-CoV-2-positive tests (2700 of 21 592 [12.5%]) compared with female patients with SARS-CoV-2-positive tests (2016 of 21 012 [9.60%]). Overall, in-hospital mortality increased from March to April (63 of 597 [10.6%] to 1047 of 5319 [19.7%]), then decreased significantly to November (499 of 5350 [9.3%]; P = .04), with significant decreases in the oldest age groups (50-64 years: 197 of 1542 [12.8%] to 73 of 1341 [5.4%]; P = .02; 65-75 years: 269 of 1182 [22.8%] to 137 of 1332 [10.3%]; P = .006; >75 years: 535 of 1479 [36.2%] to 262 of 1505 [17.4%]; P = .03). Conclusions and Relevance: This nationally representative study supported the findings of smaller, regional studies and found that in-hospital mortality declined across all age groups during the period evaluated. Reductions were unlikely because of a higher proportion of younger patients with lower in-hospital mortality in the later period.

A multicenter analysis of the clinical microbiology and antimicrobial usage in hospitalized patients in the US with or without COVID-19.

BACKGROUND: Past respiratory viral epidemics suggest that bacterial infections impact clinical outcomes. There is minimal information on potential co-pathogens in patients with coronavirus disease-2019 (COVID-19) in the US. We analyzed pathogens, antimicrobial use, and healthcare utilization in hospitalized US patients with and without severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). METHODS: This multicenter retrospective study included patients with > 1 day of inpatient admission and discharge/death between March 1 and May 31, 2020 at 241 US acute care hospitals in the BD Insights Research Database. We assessed microbiological testing data, antimicrobial utilization in admitted patients with ≥24 h of antimicrobial therapy, and length of stay (LOS). RESULTS: A total of 141,621 patients were tested for SARS-CoV-2 (17,003 [12.0%] positive) and 449,339 patients were not tested. Most (> 90%) patients tested for SARS-CoV-2 had additional microbiologic testing performed compared with 41.9% of SARS-CoV-2-untested patients. Non-SARS-CoV-2 pathogen rates were 20.9% for SARS-CoV-2-positive patients compared with 21.3 and 27.9% for SARS-CoV-2-negative and -untested patients, respectively. Gram-negative bacteria were the most common pathogens (45.5, 44.1, and 43.5% for SARS-CoV-2-positive, -negative, and -untested patients). SARS-CoV-2-positive patients had higher rates of hospital-onset (versus admission-onset) non-SARS-CoV-2 pathogens compared with SARS-CoV-2-negative or -untested patients (42.4, 22.2, and 19.5%, respectively), more antimicrobial usage (68.0, 45.2, and 25.1% of patients), and longer hospital LOS (mean [standard deviation (SD)] of 8.6 [11.4], 5.1 [8.9], and 4.2 [8.0] days) and intensive care unit (ICU) LOS (mean [SD] of 7.8 [8.5], 3.6 [6.2], and 3.6 [5.9] days). For all groups, the presence of a non-SARS-CoV-2 pathogen was associated with increased hospital LOS (mean [SD] days for patients with versus without a non-SARS-CoV-2 pathogen: 13.7 [15.7] vs 7.3 [9.6] days for SARS-CoV-2-positive patients, 8.2 [11.5] vs 4.3 [7.9] days for SARS-CoV-2-negative patients, and 7.1 [11.0] vs 3.9 [7.4] days for SARS-CoV-2-untested patients). CONCLUSIONS: Despite similar rates of non-SARS-CoV-2 pathogens in SARS-CoV-2-positive, -negative, and -untested patients, SARS-CoV-2 was associated with higher rates of hospital-onset infections, greater antimicrobial usage, and extended hospital and ICU LOS. This finding highlights the heavy burden of the COVID-19 pandemic on healthcare systems and suggests possible opportunities for diagnostic and antimicrobial stewardship.

Planning for monitoring the introduction and effectiveness of new vaccines using real-word data and geospatial visualization: An example using rotavirus vaccines with potential application to SARS-CoV-2.

BACKGROUND: Infectious diseases continue to cause significant impact on human health. Vaccines are instrumental in preventing infectious diseases and mitigating pandemics and epidemics. SARS-CoV-2 is the most recent example of an urgent pandemic that requires the development of vaccines. This study combined real-world data and geospatial visualization techniques to demonstrate methods to monitor and communicate the uptake and impact of existing and new vaccines. METHODS: Observational data of existing pediatric rotavirus vaccines were used as an example. A large US national insurance claims database was accessed to build an analytic dataset for a 20-year period (1996-2017). For each week and multiple geographic scales, animated spatial and non-spatial visualization techniques were applied to demonstrate changes in seasonal rotavirus epidemic curves and population-based disease rates before, during, and after vaccine introduction in 2006. The geographic scales included national, state, county and zip code tabulation areas. An online web-based digital atlas was built to display either continuous or snapshot visualizations of disease patterns, vaccine uptake, and improved health outcomes after vaccination (http://www.mapvaccines.com). RESULTS: Over 17 million zip code-weeks of data were available for analysis. The animations show geospatial patterns of rotavirus-related medical encounter rates peaking every year from November - February prior to vaccine availability in 2006. Visualizations showed increasing vaccination coverage rates at all geographic scales over time. Declines in medical encounter rates accelerated as vaccination coverage rapidly increased after 2010. The data maps also identified geographic hotspots with low vaccination rates and persistent disease rates. CONCLUSION: This project developed novel web-based methods to communicate location and time-based vaccine uptake and the related reduction in medical visits due to viral infection. Future applications of the visualization could be used by health agencies to monitor known or novel disease patterns over time in conjunction with close assessment of current and future vaccine utilization.

Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York City.

BACKGROUND: Although the burden of influenza is well characterized, the burden of community-onset non-influenza respiratory viruses has not been systematically assessed. Understanding the severity and seasonality of non-influenza viruses, including human coronaviruses, will provide a better understanding of the overall disease burden from respiratory viruses that could better inform resource utilization for hospitals and highlight the value of preventative strategies, including vaccines. METHODS: From October 2017 to September 2019, a retrospective study was performed in a pre-defined catchment area to estimate the population-based incidence of community-onset respiratory viruses associated with hospitalization. Included patients were ≥18 years old, resided in New York City, were hospitalized for ≥24 hours, and had a respiratory virus detected within 3 calendar-days of admission. Disease burden was measured by hospital length of stay (LOS), intensive care unit (ICU) admissions, and in-hospital mortality and compared among those with laboratory-confirmed influenza versus those with laboratory-confirmed non-influenza viruses (human coronaviruses, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and adenovirus). RESULTS: During the study period, 4232 eligible patients were identified of whom 50.9% were ≥65 years of age. For each virus, the population-based incidence was highest for those ≥80 years of age. When compared to those with influenza viruses detected, those with non-influenza respiratory viruses detected (combined) had higher population-based incidence, significantly more ICU admissions, and higher in-house mortality. CONCLUSIONS: The burden of non-influenza respiratory viruses for hospitalized adults is substantial. Prevention and treatment strategies are needed for non-influenza respiratory viruses, particularly for older adults.