Circulation of Rhinoviruses and/or Enteroviruses in Pediatric Patients With Acute Respiratory Illness Before and During the COVID-19 Pandemic in the US.

Importance: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting. Objective: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals. Design, Setting, and Participants: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought medical care for fever and/or respiratory symptoms at 7 EDs or hospitals within NVSN across the US between December 2016 and February 2021. Persons younger than 18 years were enrolled in NVSN, and respiratory specimens were collected and tested for multiple viruses. Main Outcomes and Measures: Proportion of patients in whom rhinovirus and/or enterovirus, or another virus, was detected by calendar month and by prepandemic (December 1, 2016, to March 11, 2020) or pandemic (March 12, 2020, to February 28, 2021) periods. Month-specific adjusted odds ratios (aORs) for rhinovirus and/or enterovirus-positive test results (among all tested) by setting (ED or inpatient) and age group (<2, 2-4, or 5-17 years) were calculated, comparing each month during the pandemic to equivalent months of previous years. Results: Of the 38 198 children and adolescents who were enrolled and tested, 11 303 (29.6%; mean [SD] age, 2.8 [3.7] years; 6733 boys [59.6%]) had rhinovirus and/or enterovirus-positive test results. In prepandemic and pandemic periods, rhinoviruses and/or enteroviruses were detected in 29.4% (9795 of 33 317) and 30.9% (1508 of 4881) of all patients who were enrolled and tested and in 42.2% (9795 of 23 236) and 73.0% (1508 of 2066) of those with test positivity for any virus, respectively. Rhinoviruses and/or enteroviruses were the most frequently detected viruses in both periods and all age groups in the ED and inpatient setting. From April to September 2020 (pandemic period), rhinoviruses and/or enteroviruses were detectable at similar or lower odds than in prepandemic years, with aORs ranging from 0.08 (95% CI, 0.04-0.19) to 0.76 (95% CI, 0.55-1.05) in the ED and 0.04 (95% CI, 0.01-0.11) to 0.71 (95% CI, 0.47-1.07) in the inpatient setting. However, unlike some other viruses, rhinoviruses and/or enteroviruses soon returned to prepandemic levels and from October 2020 to February 2021 were detected at similar or higher odds than in prepandemic months in both settings, with aORs ranging from 1.47 (95% CI, 1.12-1.93) to 3.01 (95% CI, 2.30-3.94) in the ED and 1.36 (95% CI, 1.03-1.79) to 2.44 (95% CI, 1.78-3.34) in the inpatient setting, and in all age groups. Compared with prepandemic years, during the pandemic, rhinoviruses and/or enteroviruses were detected in patients who were slightly older, although most (74.5% [1124 of 1508]) were younger than 5 years. Conclusions and Relevance: Results of this study show that rhinoviruses and/or enteroviruses persisted and were the most common respiratory virus group detected across all pediatric age groups and in both ED and inpatient settings. Rhinoviruses and/or enteroviruses remain a leading factor in ARI health care burden, and active ARI surveillance in children and adolescents remains critical for defining the health care burden of respiratory viruses.

Life-Threatening Complications of Influenza versus COVID-19 in U.S. Children.

BACKGROUND: Clinical differences between critical illness from influenza infection versus coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. METHODS: We compared U.S. children (8 months to 17 years) admitted to the intensive care or high acuity unit with influenza (17 hospitals, 12/19/2019-3/9/2020) or COVID-19 (52 hospitals, 3/15/2020-12/31/2020). We compared demographics, underlying conditions, clinical presentation, severity, and outcomes. Using mixed-effects models, we assessed the odds of death or requiring life-support for influenza versus COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. RESULTS: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median 5.2 vs. 13.8 years), less likely to be non-Hispanic black (14.5% vs. 27.6%) or Hispanic (24.0% vs. 36.2%), and less likely to have ≥1 underlying condition (66.4% vs. 78.5%) or be obese (21.4% vs. 42.2%). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life-support in children with influenza vs. COVID-19 were similar (adjusted odds ratio, 1.30 [95% CI: 0.78-2.15; P = 0.32]). Median duration of hospital stay was shorter for influenza than COVID-19 (5 versus 7 days). CONCLUSIONS: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.

Respiratory pathogens during the COVID-19 pandemic: Alterations in detection and seasonality in Nashville, Tennessee.

Shortly after the implementation of community mitigation measures in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), sharp declines in respiratory syncytial virus and influenza circulation were noted; post-mitigation circulation of other respiratory pathogens has gone unexplored. We retrospectively analyzed all records of a provider-ordered multiplex test between April 1, 2018, and July 31, 2021, in Nashville, Tennessee, and we noted disrupted historical seasonal patterns for common respiratory pathogens during the SARS-CoV-2 pandemic.

Comparison of clinical presentations and burden of respiratory syncytial virus in infants across three distinct healthcare settings in Davidson County, Tennessee.

Background: The burden of respiratory syncytial virus (RSV)-associated acute respiratory illnesses among healthy infants (<1 year) in the inpatient setting is well established. The focus on RSV-associated illnesses in the outpatient (OP) and emergency department (ED) settings are however understudied. We sought to determine the spectrum of RSV illnesses in infants at three distinct healthcare settings. Methods: From 16 December 2019 through 30 April 2020, we performed an active, prospective RSV surveillance study among infants seeking medical attention from an inpatient (IP), ED, or OP clinic. Infants were eligible if they presented with fever and/or respiratory symptoms. Demographics, clinical characteristics, and illness histories were collected during parental/guardian interviews, followed by a medical chart review and illness follow-up surveys. Research nasal swabs were collected and tested for respiratory pathogens for all enrolled infants. Results: Of the 627 infants screened, 475 were confirmed eligible; 360 were enrolled and research tested. Within this final cohort, 101 (28%) were RSV-positive (IP = 37, ED = 18, and OP = 46). Of the RSV-positive infants, the median age was 4.5 months and 57% had ⩾2 healthcare encounters. The majority of RSV-positive infants were not born premature (88%) nor had underlying medical conditions (92%). RSV-positive infants, however, were more likely to have a lower respiratory tract infection than RSV-negative infants (76% vs 39%, p < 0.001). Hospitalized infants with RSV were younger, 65% required supplemental oxygen, were more likely to have lower respiratory tract symptoms, and more often had shortness of breath and rales/rhonchi than RSV-positive infants in the ED and OP setting. Conclusion: Infants with RSV illnesses seek healthcare for multiple encounters in various settings and have clinical difference across settings. Prevention measures, especially targeted toward healthy, young infants are needed to effectively reduce RSV-associated healthcare visits.

Clinical presentations of adult and pediatric SARS-CoV-2-positive cases in a community cohort, Nashville, Tennessee.

Compared to adults, the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness in children has been lower and less severe. However, reports comparing SARS-CoV-2 infection among children and adults are limited. As part of our longitudinal cohort study of adults and children with SARS-CoV-2 infection and their household contacts in Nashville, Tennessee, we compared the clinical characteristics and outcomes of SARS-CoV-2 infections between children and adults. Children were more likely to be asymptomatically infected and had a shorter illness duration compared to adults. The differences observed in clinical presentation across ages may inform symptom-specific testing, screening, and management algorithms.

Humoral and cellular immune responses to the SARS-CoV-2 BNT162b2 vaccine among a cohort of solid organ transplant recipients and healthy controls.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased morbidity and mortality in solid organ transplant (SOT) recipients. Despite exclusion from SARS-CoV-2 vaccine clinical trials, these individuals were identified as high-risk and prioritized for vaccination in public health guidelines. METHODS: We prospectively evaluated humoral and cellular immune responses to two doses of the SARS-CoV-2 mRNA vaccine, BNT162b2, in 56 SOT recipients and 26 healthy controls (HCs). Blood specimens collected from participants prior to each dose and following the second dose were tested for SARS-CoV-2-specific antibodies, as well as CD4+ and CD8+ T-cell responses. RESULTS: SOT recipients demonstrated lower mean anti-SARS-CoV-2 antibody levels compared to HCs after each dose, and only 21.6% achieved an antibody response after the second dose within the range of HC responses. Similarly, the percentage of responsive CD4+ and CD8+ T cells in SOT recipients was lower than in HCs. While most HCs showed notable humoral and cellular responses, responses were less concordant in SOT recipients, with some showing evidence of either humoral or cellular response, but not both. CONCLUSION: Humoral and cellular immune responses to the BNT162b2 vaccine are markedly reduced in SOT recipients as compared to HCs, suggesting that SOT recipients may benefit from more tailored regimens such as higher dose and/or additional vaccinations.

Acute Respiratory Illnesses in Children During the sars-cov-2 Pandemic: A Prospective Multicenter Surveillance Study

Background: A state of emergency was declared in the United States (US) on March 13, 2020 in response to the SARS-CoV-2 pandemic. Healthcare providers had to alter practice patterns and research priorities. We assessed the frequency of acute respiratory illnesses (ARI) in children, notably those due to respiratory syncytial virus (RSV) and influenza, before and during the pandemic. Methods: We conducted multi-center active prospective ARI surveillance in children as part of the New Vaccine Surveillance Network. Children < 18 years with fever and/or respiratory symptoms were enrolled in emergency department and inpatient settings at seven US medical centers over four respiratory seasons during 2016-2020 (Fig 1). Pandemic-related restrictions to patient access limited enrollment in some sites beginning March 2020. Respiratory specimens were collected and tested at each site for RSV and influenza by qRT-PCR. Data were analyzed by calendar weeks. We compared the cumulative proportions of RSV and influenza detection after week 13 in 2020 to the previous seasons using Fisher's exact test. Results: Of 44,247 eligible children, 25,375 (57%) were enrolled and tested for RSV and/or influenza. A total of 6351/25375 (25%) and 3446/25372 (14%) children were RSV and influenza-positive over the four seasons, respectively. In 2020, we noted a rapid drop in eligible and enrolled ARI subjects after weeks 11-13 (Fig 1). During weeks 13-18 in 2016-2019, the three-year average of eligible and enrolled subjects was 1802 and 978, respectively. However, over the same period in 2020, there were 675 eligible and 278 enrolled subjects, representing declines of 62.5% and 71.6% respectively (Fig 1). In 2020, there were no RSV or influenza cases detected in weeks 15-18, and the cumulative proportions of RSV and influenza detection after week 13 were lower compared to previous seasons (p< 0.001) (Figs 1 and 2). Conclusion: There was a considerable decline in ARI visits and the proportion of RSV and influenza detection across seven distinct geographic sites during the pandemic compared with previous seasons. These findings might be attributable to social distancing measures to lessen the spread of SARS-CoV-2, changes in healthcare-seeking behaviors, and limited access to medical care. (Table Presented).

Acute Respiratory Illnesses in Children in the SARS-CoV-2 Pandemic: Prospective Multicenter Study.

OBJECTIVES: Nonpharmaceutical interventions against coronavirus disease 2019 likely have a role in decreasing viral acute respiratory illnesses (ARIs). We aimed to assess the frequency of respiratory syncytial virus (RSV) and influenza ARIs before and during the coronavirus disease 2019 pandemic. METHODS: This study was a prospective, multicenter, population-based ARI surveillance, including children seen in the emergency departments and inpatient settings in 7 US cities for ARI. Respiratory samples were collected and evaluated by molecular testing. Generalized linear mixed-effects models were used to evaluate the association between community mitigation and number of eligible and proportion of RSV and influenza cases. RESULTS: Overall, 45 759 children were eligible; 25 415 were enrolled and tested; 25% and 14% were RSV-positive and influenza-positive, respectively. In 2020, we noted a decrease in eligible and enrolled ARI subjects after community mitigation measures were introduced, with no RSV or influenza detection from April 5, 2020, to April 30, 2020. Compared with 2016-2019, there was an average of 10.6 fewer eligible ARI cases per week per site and 63.9% and 45.8% lower odds of patients testing positive for RSV and influenza, respectively, during the 2020 community mitigation period. In all sites except Seattle, the proportions of positive tests for RSV and influenza in the 2020 community mitigation period were lower than predicted. CONCLUSIONS: Between March and April 2020, rapid declines in ARI cases and the proportions of RSV and influenza in children were consistently noted across 7 US cities, which could be attributable to community mitigation measures against severe acute respiratory syndrome coronavirus 2.

Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons.

OBJECTIVE: The World Health Organization created the Severe Acute Respiratory Infection (SARI) criteria in 2011 to monitor influenza (flu)-related hospitalization. Many studies have since used the SARI case definition as inclusion criteria for surveillance studies. We sought to determine the sensitivity, specificity, positive predictive value, and negative predictive value of the SARI criteria for detecting ten different respiratory viruses in a Middle Eastern pediatric cohort. MATERIALS AND METHODS: The data for this study comes from a prospective acute respiratory surveillance study of hospitalized children <2 years in Amman, Jordan from March 16, 2010 to March 31, 2013. Participants were recruited if they had a fever and/or respiratory symptoms. Nasal and throat swabs were obtained and tested by real-time RT-PCR for eleven viruses. Subjects meeting SARI criteria were determined post-hoc. Sensitivity, specificity, positive predictive value, and negative predictive value of the SARI case definition for detecting ten different viruses were calculated and results were stratified by age. RESULTS: Of the 3,175 patients enrolled, 3,164 were eligible for this study, with a median age of 3.5 months, 60.4% male, and 82% virus-positive (44% RSV and 3.8% flu). The sensitivity and specificity of the SARI criteria for detecting virus-positive patients were 44% and 77.9%, respectively. Sensitivity of SARI criteria for any virus was lowest in children <3 months at 22.4%. Removing fever as a criterion improved the sensitivity by 65.3% for detecting RSV in children <3 months; whereas when cough was removed, the sensitivity improved by 45.5% for detecting flu in same age group. CONCLUSIONS: The SARI criteria have poor sensitivity for detecting RSV, flu, and other respiratory viruses-particularly in children <3 months. Researchers and policy makers should use caution if using the criteria to estimate burden of disease in children.