Jon Fryzek

Background: Respiratory 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.Methods: Studies 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.Results: Eighty 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.Conclusions: Not all infants and children with LRTI are tested for RSV, highlighting underestimation of RSV burden across all settings.

Background: Surveillance in 2020–2021 showed that seasonal respiratory illnesses were below levels seen during prior seasons, with the exception of interseasonal respiratory syncytial virus (RSV). Methods: Electronic health record data of infants aged <1 year visiting the Duke University Health System from 4 October 2015 to 28 March 2020 (pre–COVID-19) and 29 March 2020 to 30 October 2021 (COVID-19) were assessed. International Classification of Diseases-Tenth Revision (ICD-10) codes for RSV (B97.4, J12.1, J20.5, J21.0) and bronchiolitis (RSV codes plus J21.8, J21.9) were used to detail encounters in the inpatient (IP), emergency department (ED), outpatient (OP), urgent care (UC), and telemedicine (TM) settings. Results: Pre–COVID-19, 88% of RSV and 92% of bronchiolitis encounters were seen in ambulatory settings. During COVID-19, 94% and 93%, respectively, occurred in ambulatory settings. Pre–COVID-19, the highest RSV proportion was observed in December–January (up to 38% in ED), while the peaks during COVID-19 were seen in July–September (up to 41% in ED) across all settings. RSV laboratory testing among RSV encounters was low during pre–COVID-19 (IP, 51%; ED, 51%; OP, 41%; UC, 84%) and COVID-19 outside of UC (IP, 33%; ED, 47%; OP, 47%; UC, 87%). Full-term, otherwise healthy infants comprised most RSV encounters (pre–COVID-19, up to 57% in OP; COVID-19, up to 82% in TM). Conclusions: With the interruption of historical RSV epidemiologic trends and the emergence of interseasonal disease during COVID-19, continued monitoring of RSV is warranted across all settings as the changing RSV epidemiology could affect the distribution of health care resources and public health policy.

Background: A systematic literature review was conducted to summarize the mortality (overall and by disease severity factors) of US infants and children aged <5 years with respiratory syncytial virus (RSV) or all-cause bronchiolitis (ACB). Methods: Comprehensive, systematic literature searches were conducted; articles were screened using prespecified eligibility criteria. A standard risk of bias tool was used to evaluate studies. Mortality was extracted as the rate per 100 000 or the case fatality ratio (CFR; proportion of deaths among RSV/ACB cases). Results: Among 42 included studies, 36 evaluated inpatient deaths; 10 used nationally representative populations updated through 2013, and only 2 included late-preterm/full-term otherwise healthy infants and children. The RSV/ACB definition varied across studies (multiple International Classification of Diseases [ICD] codes; laboratory confirmation); no study reported systematic testing for RSV. No studies reported RSV mortality rates, while 3 studies provided ACB mortality rates (0.57–9.4 per 100 000). CFRs ranged from 0% to 1.7% for RSV (n = 15) and from 0% to 0.17% for ACB (n = 6); higher CFRs were reported among premature, intensive care unit-admitted, and publicly insured infants and children. Conclusions: RSV mortality reported among US infants and children is variable. Current, nationally representative estimates are needed for otherwise healthy, late-preterm to full-term infants and children.

Background: The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized. Methods: We systematically reviewed studies of RSV and bronchiolitis published 2000–2021 (data years, 1979–2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools. Results: We identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6–11 months in 2006 to 50.1 per 1000 per year among infants aged 0–2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0–22.7 per 1000 in 1997–1999 and 1997–2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non–high-risk infants in 1997-2012. Conclusions: Substantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.

Respiratory syncytial virus (RSV) is the leading cause of hospitalizations in United States infants aged P = .5), whereas ED visit rates increased (P = .004). From 2011 through 2019, Medicaid infants had the highest average rates (RSVH: 22.3 [95% confidence interval {CI}, 21.5–23.1] per 1000; ED visits: 55.9 [95% CI, 52.4–59.4] per 1000) compared to infants with private or other/unknown insurance (RSVH: P < .0001; ED visits: P < .0001). From 2011 through 2019, for all races and ethnicities, Medicaid infants had higher average RSVH rates (up to 7 times) compared to infants with private or other/unknown insurance. RSVH mortality remained constant over time (P = .8), whereas MV use (2019: 13% of RSVH, P < .0001) and mean charge during hospitalization (2019: $21 513, P < .0001) increased. Bronchiolitis patterns were similar. This study highlights the importance of ensuring access to RSV preventive measures for all infants.

Background: This study describes leading causes of hospitalization, including respiratory syncytial virus (RSV), in United States infants (10% of total infant hospitalizations from December through March, reaching >15% in January–February. From 2009 through 2011, acute bronchiolitis due to RSV was the leading primary diagnosis in every birth month. Acute bronchiolitis due to RSV was the leading cause among all races/ethnicities, except Asian/Pacific Islanders, and all insurance payer groups. KID analyses confirmed these results. Conclusions: Acute bronchiolitis due to RSV is the leading cause of US infant hospitalizations.

Infant mortality due to respiratory syncytial virus (RSV) in the United States is not well understood. From 1999 to 2018, RSV, bronchiolitis, and influenza deaths were described for infants P = .0327). These national estimates emphasize the importance of considering all infants across all healthcare settings when describing RSV mortality.

Respiratory syncytial virus (RSV) accounts for the majority of lower respiratory tract illnesses in hospitalized infants. In the U.S., RSV hospitalizations are well characterized; yet, emergency department (ED) and outpatient (OP) visits are underrecognized. We evaluated the burden of RSV across three distinct healthcare settings during one respiratory season. From 12/16/19-4/30/20, we conducted a prospective RSV surveillance study among Davidson County, TN infants under one year who presented to an inpatient (IP), ED, or one of four OP clinics with either fever or any upper respiratory (i.e., cough, earache, nasal congestion, rhinorrhea, sore throat) and/or lower respiratory [i.e., wheezing, crackles, rales, diminished breath sounds, shortness of breath (SOB)] symptoms. Demographic and illness history were collected during parental/guardian interviews, followed by medical chart abstraction. Nasal swabs were collected and tested for RSV using Luminex® NxTAG RPP. Due to the COVID-19 pandemic, on 3/16/20 enrollment at three of the four OP clinics ceased. A total of 627 infants were screened, of whom 473 (75%) were confirmed eligible, 364 (77%) enrolled, 361 (99%) were tested for RSV of which 101 (28%) were RSV+ (IP=37, ED=18, OP=46) (Figure 1). Compared to RSV-negative subjects, RSV+ subjects were younger (6.6 vs. 4.9 months, p< 0.001), 56% were male and 48% white. By setting, infants in the OP setting were older than those seen in the IP and ED [(p=0.002), Figure 2]. Compared to infants in the OP setting, hospitalized infants were more likely to present with SOB and rhonchi/rales, but less likely to have only upper respiratory symptoms (Figure 3) and be African American (p=0.046). Infants in the IP setting had a higher proportion of clinical RSV diagnostic testing (73%) compared to the ED (39%) and OP (28%) settings (p< 0.001). Figure 1. Davidson County Infants with RSV by MMWR Week and Healthcare Setting (n=101) Figure 2. Cumulative Enrollment of Davidson County Infants with RSV by Age in Months and Healthcare Setting (n=101) Figure 3. Proportion of Davidson County Infants with RSV Showing each Clinical Symptom, by Healthcare Setting Two-thirds of RSV+ infants sought care from either an OP or ED setting, with nearly all hospitalized infants presenting with both upper and lower respiratory symptoms. The underutilization of diagnostic testing in the OP settings may underestimate the true burden of RSV. Future studies are essential to document the true prevalence of RSV in order to assess the need and impact of new interventions (e.g., immunizations, antivirals). Danielle A. Rankin, MPH, CIC, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Zaid Haddadin, MD, CDC (Grant/Research Support, Research Grant or Support)Quidel Corporation (Grant/Research Support, Research Grant or Support)sanofi pasteur (Grant/Research Support, Research Grant or Support) Jon Fryzek, PhD, MPH, EpidStrategies (Employee) Mina Suh, MPH, International Health, EpidStrategies (Employee) Donald S. Shepard, PhD, Sanofi Pasteur (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

Few data exist on the occurrence of metastatic basal cell carcinoma (mBCC). To identify all cases of mBCC in Denmark over a 14-year period. We searched the Danish National Patient Registry covering all Danish hospitals, the Danish Cancer Registry, the National Pathology Registry and the Causes of Death Registry during the period 1997 to 2010 for potential cases of mBCC registered according to the International classification of diseases ICD-10 and the International Systemized Nomenclature of Medicine (SNOMED). We identified 126,627 patients with a history of primary basal cell carcinoma (BCC) in the registries during the 14-year study period. Using case identifications from the four registries, a total of 170 potential mBCC cases were identified. However, after a pathology review, only five cases could be confirmed, of which three were basosquamous carcinomas. The 14-year cumulative incidence proportion of mBCC was 0.0039% (95% CI 0.0016-0.0083) among individuals with a history of previous BCC (n = 126,627) and 0.0001% (95% CI 0.0000-0.0002) in the general population. MBCC is a rare disease and only a small proportion of potential cases identified in automated clinical databases or registries can be confirmed by pathology and medical record review.