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.

SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021.

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25-3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. IMPORTANCE SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.

Healthcare-associated respiratory syncytial virus infections in children's hospitals

Background: Little is known about the impact of healthcare-associated respiratory syncytial virus (HA-RSV) in hospitalized children. To address this gap, we assessed the epidemiology and clinical impact associated with HA-RSV in a multiseason, multicenter study. Methods: During respiratory viral seasons 2016–2017, 2017–2018, and 2018–2019, we retrospectively identified HA-RSV cases in hospitalized children 72 hours after admission or within 48 hours of discharge in readmitted patients. Due to reduced availability of testing for non–SARS-CoV-2 viruses during the first year of the COVID-19 pandemic, the 2019–2020 season was excluded. We initiated prospective HA-RSV surveillance during the 2020–2021 season and continued surveillance through November 2021 due to the unusual interseasonal RSV community outbreak. We determined demographic and clinical characteristics of HA-RSV cases and explored possible outcomes associated with RSV including transfer to the pediatric ICU and escalation of respiratory support from day −2 to day +4 (day 0 was the day of RSV detection). We explored the timeframe of day −2 to day +4 because events during this timeframe could be attributed to RSV infection. Respiratory support escalation was defined as change from room air to supplemental oxygen, increase in fraction of inspired oxzygen (FiO2) on same respiratory support modality, or change from noninvasive to invasive support. Results: Were identified 86 HA-RSV cases: 20 (23.3%) from 2016–2017, 26 (30.2%) from 2017–2018, 34 (39.5%) from 2018–2019, and 6 (7%) from October 2020–November 2021. HA-RSV was diagnosed a median of 14 days (IQR, 8–45) after admission. Moreover, 29 (33.7%), 31 (36.0%), and 26 (30.2%) cases were aged 60 months during these, respective seasons. Also, 33 (38.4%) had >3 comorbid conditions, most commonly gastrointestinal (n = 33, 38.4%), respiratory (n = 28, 32.6%), and/or congenital–genetic disorders (n = 28, 32.6%). However, 9 (10.5%) had no comorbid conditions. From day −2 to day +4, 15 children (17.4%) were transferred to the PICU and 38 (49.3%) of 77 evaluable cases required respiratory support escalation, most commonly supplemental oxygen delivered by nasal cannula (n = 15, 19.5%). Furthermore, 11 patients (14.3%) required invasive support. Conclusions: HA-RSV was associated with use of healthcare resources, including the need for respiratory support escalation and/or transfer to intensive care. From October 2020 to November 2021, lower numbers of HA-RSV were observed. The reasons for this are unknown, but potentially occurred in parallel to markedly reduced RSV in the community and may have resulted from visitor restrictions, which included no siblings and/or universal masking by hospital staff and visitors.Funding: Funding for this research was provided by Merck Sharp & Dohme, a subsidiary of Merck & Co.Disclosures: None

Keeping It Real: Infection Prevention and Control Problems and Solutions in Low- and Middle-income Countries.

Infection prevention challenges are ubiquitous in healthcare, but some are unique to or more prevalent in low-and middle-income country settings. Despite limited resources, innovative and committed paediatric healthcare providers and infection preventionists have found creative solutions to address the very real and pressing risks their patients face every day. We gathered examples of infection prevention and control challenges faced by clinicians in resource-limited healthcare facilities, and the real-world infection prevention and control solutions they implemented, with the goal of learning broader lessons applicable to low-and middle-income countrie.

Dodging the bundle-Persistent healthcare-associated rhinovirus infection throughout the pandemic.

INTRODUCTION: Healthcare-associated viral infections (HAVI) are a common cause of patient harm in the pediatric population. We implemented a HAVI prevention bundle in 2015, which included 6 core elements: caregiver screening, symptom-based isolation, personal protective equipment (PPE), hand hygiene, staff illness procedures, and monitoring of environmental cleanliness. Enhanced bundle elements were introduced at the start of the COVID-19 pandemic, which provided an opportunity to observe the effectiveness of the bundle with optimal adherence to prevention practices, and to measure the impact on respiratory HAVI epidemiology. METHODS: Respiratory HAVIs were confirmed through review of medical records and application of the National Health Safety Network (NHSN) surveillance criteria for upper respiratory infections (URIs) with predetermined incubation periods for unit attribution. Descriptive statistics of the study population were examined, and comparative analyses were performed on demographic and process metrics. Data analysis was conducted using R statistical software. RESULTS: We observed an overall decrease in respiratory HAVI of 68%, with prepandemic rates of 0.19 infections per 1,000 patient significantly decreased to a rate of 0.06 per 1,000 patient days in the pandemic period (P < .01). Rhinovirus made up proportionally more of our respiratory HAVI in the pandemic period (64% vs 53%), with respiratory HAVI secondary only to rhinovirus identified during 8 of 16 months in the pandemic period. Compliance with our HAVI prevention bundle significantly improved during pandemic period. CONCLUSIONS: Enhancement of our HAVI bundle during the COVID-19 pandemic contributed toward significant reduction in nosocomial transmission of respiratory HAVI. Even with prevention practices optimized, respiratory HAVIs secondary to rhinovirus continued to be reported, likely due to the capacity of rhinovirus to evade bundle elements in hospital, and infection prevention efforts at large in the community, leaving vulnerable patients at continued risk.

Comparison of Antimicrobial Stewardship and Infection Prevention and Control Activities and Resources Between Low-/Middle- and High-income Countries.

BACKGROUND: The growth of antimicrobial resistance worldwide has led to increased focus on antimicrobial stewardship (AMS) and infection prevention and control (IPC) measures, although primarily in high-income countries (HIC). We aimed to compare pediatric AMS and IPC resources/activities between low- and middle-income countries (LMIC) and HIC and to determine the barriers and priorities for AMS and IPC in LMIC as assessed by clinicians in those settings. METHODS: An online questionnaire was distributed to clinicians working in HIC and LMIC healthcare facilities in 2020. RESULTS: Participants were from 135 healthcare settings in 39 LMIC and 27 HIC. Formal AMS and IPC programs were less frequent in LMIC than HIC settings (AMS 42% versus 76% and IPC 58% versus 89%). Only 47% of LMIC facilities conducted audits of antibiotic use for pediatric patients, with less reliable availability of World Health Organization Access list antibiotics (29% of LMIC facilities). Hand hygiene promotion was the most common IPC intervention in both LMIC and HIC settings (82% versus 91%), although LMIC hospitals had more limited access to reliable water supply for handwashing and antiseptic hand rub. The greatest perceived barrier to pediatric AMS and IPC in both LMIC and HIC was lack of education: only 17% of LMIC settings had regular/required education on antimicrobial prescribing and only 25% on IPC. CONCLUSIONS: Marked differences exist in availability of AMS and IPC resources in LMIC as compared with HIC. A collaborative international approach is urgently needed to combat antimicrobial resistance, using targeted strategies that address the imbalance in global AMS and IPC resource availability and activities.

The Effectiveness Of Government Masking Mandates On COVID-19 County-Level Case Incidence Across The United States, 2020.

Evidence for the effectiveness of masking on SARS-CoV-2 transmission at the individual level has accumulated, but the additional benefit of community-level mandates is less certain. In this observational study of matched cohorts from 394 US counties between March 21 and October 20, 2020, we estimated the association between county-level public masking mandates and daily COVID-19 case incidence. On average, the daily case incidence per 100,000 people in masked counties compared with unmasked counties declined by 23 percent at four weeks, 33 percent at six weeks, and 16 percent across six weeks postintervention. The beneficial effect varied across regions of different population densities and political leanings. The most concentrated effects of masking mandates were seen in urban counties; the benefit of the mandates was potentially stronger within Republican-leaning counties. Although benefits were not equally distributed in all regions, masking mandates conferred benefit in reducing community case incidence during an early period of the COVID-19 pandemic.

Evolution of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroprevalence among employees of a US academic children's hospital during coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study open to adult employees at the Children's Hospital of Philadelphia, conducted April 20-December 17, 2020. METHODS: Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity. RESULTS: In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03-3.68), Black race (HR, 2.70; 95% CI, 1.24-5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71-6.88) were associated with statistically significant increased risk for seropositivity. CONCLUSIONS: Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.

The COVID trap: pediatric diagnostic errors in a pandemic world.

OBJECTIVES: The COVID-19 pandemic has introduced strains in the diagnostic process through uncertainty in diagnosis, changes to usual clinical processes, and introduction of a unique social context of altered health care delivery and fear of the medical environment. These challenges created a context ripe for diagnostic error involving both systems and cognitive factors. CASE PRESENTATION: We present a series of three pediatric cases presenting to care during the early phases of the COVID-19 pandemic that highlight the heightened potential for diagnostic errors in the pandemic context with particular focus on the interplay of systems and cognitive factors leading to delayed and missed diagnoses. These cases illustrate the particular power of availability bias, diagnostic momentum, and premature closure in the diagnostic process. CONCLUSIONS: Through integrated commentary and a fishbone analysis of the cognitive and systems factors at play, these three cases emphasize the specific influence of the COVID-19 pandemic on pediatric patients.

Comparative Analysis of Emerging B.1.1.7+E484K SARS-CoV-2 Isolates.

We report the genome of a B.1.1.7+E484K severe acute respiratory syndrome coronavirus 2 from Southeastern Pennsylvania and compare it with all high-coverage B.1.1.7+E484K genomes (n = 235) available. Analyses showed the existence of at least 4 distinct clades of this variant circulating in the United States and the possibility of at least 59 independent acquisitions of the E484K mutation.

The utility of paired upper and lower respiratory tract sampling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in patients with artificial airways.

Early in the coronavirus disease 2019 (COVID-19) pandemic, the CDC recommended collection of a lower respiratory tract (LRT) specimen for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing in addition to the routinely recommended upper respiratory tract (URT) testing in mechanically ventilated patients. Significant operational challenges were noted at our institution using this approach. In this report, we describe our experience with routine collection of paired URT and LRT sample testing. Our results revealed a high concordance between the 2 sources, and that all children tested for SARS-CoV-2 were appropriately diagnosed with URT testing alone. There was no added benefit to LRT testing. Based on these findings, our institutional approach was therefore adjusted to sample the URT alone for most patients, with LRT sampling reserved for patients with ongoing clinical suspicion for SARS-CoV-2 after a negative URT test.

Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. Objective: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. Design, Setting, and Participants: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. Exposures: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). Main Outcomes and Measures: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. Results: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). Conclusions and Relevance: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

The Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in a Pediatric Healthcare Network in the United States.

BACKGROUND: Understanding the prevalence and clinical presentation of coronavirus disease 2019 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic. METHODS: This was a retrospective case series of patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across a pediatric healthcare network, including clinical features and outcomes of those with positive test results. RESULTS: Of 7256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients aged 18-21 years had the highest test positive rate (11.2%), while those aged 1-5 years had the lowest (3.9%). By race, 10.6% (226/2132) of black children tested positive vs 3.3% (117/3592) of white children. By indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs 3.8% (53/1410) of those undergoing preprocedural or preadmission testing. Of 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbidities, 87 (20.5%) had asthma, and 55 (13.0%) were obese. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2-positive patients were hospitalized, of whom 24 (31.2%) required respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2-positive patients required mechanical ventilation, and 2 patients required extracorporeal membrane oxygenation. Two patients died. CONCLUSIONS: In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low but varied by testing indication. The majority of cases were mild and few children had critical illness.