Nausea, Vomiting, and Diarrhea Are Common in Community-Acquired Acute Viral Respiratory Illness.

BACKGROUND: Gastrointestinal (GI) symptoms are recognized sequelae of acute respiratory illness (ARI), but their prevalence is not well documented. Our study aim was to assess the incidence of GI symptoms in community ARI cases for persons of all ages and their association with clinical outcomes. METHODS: We collected mid-nasal swabs, clinical, and symptom data from Seattle-area individuals during the 2018-2019 winter season as part of a large-scale prospective community surveillance study. Swabs were tested by polymerase chain reaction (PCR) for 26 respiratory pathogens. Likelihood of GI symptoms given demographic, clinical, and microbiological covariates were analyzed with Fisher's exact, Wilcoxon-rank-sum, and t-tests and multivariable logistic regression. RESULTS: In 3183 ARI episodes, 29.4% had GI symptoms (n = 937). GI symptoms were significantly associated with pathogen detection, illness interfering with daily life, seeking care for the illness, and greater symptom burden (all p < 0.05). Controlling for age, > 3 symptoms, and month, influenza (p < 0.001), human metapneumovirus (p = 0.004), and enterovirus D68 (p = 0.05) were significantly more likely to be associated with GI symptoms than episodes with no pathogen detected. Seasonal coronaviruses (p = 0.005) and rhinovirus (p = 0.04) were significantly less likely to be associated with GI symptoms. CONCLUSION: In this community-surveillance study of ARI, GI symptoms were common and associated with illness severity and respiratory pathogen detection. GI symptoms did not track with known GI tropism, suggesting GI symptoms may be nonspecific rather than pathogen-mediated. Patients presenting with GI and respiratory symptoms should have respiratory virus testing, even if the respiratory symptom is not the primary concern.

Paediatric healthcare and hospital worker SARS-CoV-2 IgG antibody: A longitudinal cohort study.

Background: This study sought to determine the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) and spike (S) protein immunoglobulin G (IgG) antibodies in healthcare and hospital workers (HCHWs), and changes in IgG N antibody levels over time. Methods: Longitudinal study of HCHWs at a freestanding, urban paediatric tertiary care hospital. Asymptomatic HCHWs aged ≥18 years working in clinical areas were eligible to enrol. Participants completed four surveys and blood draws over 12 months. Specimens were tested for IgG N at four timepoints and IgG S at 12 months. Results: In total, 531 HCHWs enrolled in this study; of these, 481 (91%), 429 (81%) and 383 (72%) completed follow-up blood draws at 2, 6 and 12 months, respectively. Five of 531 (1%), 5/481 (1%), 6/429 (1%) and 5/383 (1.3%) participants were seropositive for IgG N at baseline, 2, 6 and 12 months, respectively. All (374/374; 100%) participants who received one or two doses of either mRNA COVID-19 vaccine were seropositive for IgG S. One of nine unvaccinated participants was seropositive for IgG S. Conclusions: In this paediatric hospital, IgG N and IgG S were detected in 1.9% and 97.9% of HCHWs, respectively. This study demonstrated low transmission of SARS-CoV-2 among HCHWs with appropriate infection prevention measures.

School-Based Interventions to Increase Student COVID-19 Vaccination Coverage in Public School Populations with Low Coverage - Seattle, Washington, December 2021-June 2022.

COVID-19 can lead to severe outcomes in children (1). Vaccination decreases risk for COVID-19 illness, severe disease, and death (2). On December 13, 2020, CDC recommended COVID-19 vaccination for persons aged ≥16 years, with expansion on May 12, 2021, to children and adolescents (children) aged 12-15 years, and on November 2, 2021, to children aged 5-11 years (3). As of March 8, 2023, COVID-19 vaccination coverage among school-aged children remained low nationwide, with 61.7% of children aged 12-17 years and approximately one third (32.7%) of those aged 5-11 years having completed the primary series (3). Intention to receive COVID-19 vaccine and vaccination coverage vary by demographic characteristics, including race and ethnicity and socioeconomic status (4-6). Seattle Public Schools (SPS) implemented a program to increase COVID-19 vaccination coverage during the 2021-22 school year, focusing on children aged 5-11 years during November 2021-June 2022, with an added focus on populations with low vaccine coverage during January 2022-June 2022.† The program included strategic messaging, school-located vaccination clinics, and school-led community engagement. Vaccination data from the Washington State Immunization Information System (WAIIS) were analyzed to examine disparities in COVID-19 vaccination by demographic and school characteristics and trends over time. In December 2021, 56.5% of all SPS students, 33.7% of children aged 5-11 years, and 81.3% of children aged 12-18 years had completed a COVID-19 primary vaccination series. By June 2022, overall series completion had increased to 80.3% and was 74.0% and 86.6% among children aged 5-11 years and 12-18 years, respectively. School-led vaccination programs can leverage community partnerships and relationships with families to improve COVID-19 vaccine access and coverage.

Monoclonal Antibody and Antiviral Therapy for Mild-to-Moderate COVID-19 in Pediatric Patients.

Multiple antiviral and monoclonal antibody therapies are now available for mild-moderate COVID-19 in high-risk patients ≥12 years of age. However, data for the use of these agents in children is limited. We reviewed 94 pediatric patients for whom early therapy was requested since the emergence of the Omicron variant and describe patient characteristics, treatment logistics and associated short-term events.

Evaluation of BNT162b2 Covid-19 Vaccine in Children Younger than 5 Years of Age.

BACKGROUND: Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children. METHODS: We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2-3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-µg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-µg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 µg of BNT162b2 in the pivotal trial. RESULTS: During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-µg dose) and 48 children 2 to 4 years of age (3-µg or 10-µg dose). The 3-µg dose level was selected for the phase 2-3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases). CONCLUSIONS: A three-dose primary series of 3-µg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

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.

The clinical and genomic epidemiology of seasonal human coronaviruses in congregate homeless shelter settings: A repeated cross-sectional study.

Background: The circulation of respiratory viruses poses a significant health risk among those residing in congregate settings. Data are limited on seasonal human coronavirus (HCoV) infections in homeless shelter settings. Methods: We analysed data from a clinical trial and SARS-CoV-2 surveillance study at 23 homeless shelter sites in King County, Washington between October 2019-May 2021. Eligible participants were shelter residents aged ≥3 months with acute respiratory illness. We collected enrolment data and nasal samples for respiratory virus testing using multiplex RT-PCR platform including HCoV. Beginning April 1, 2020, eligibility expanded to shelter residents and staff regardless of symptoms. HCoV species was determined by RT-PCR with species-specific primers, OpenArray assay or genomic sequencing for samples with an OpenArray relative cycle threshold <22. Findings: Of the 14,464 samples from 3281 participants between October 2019-May 2021, 107 were positive for HCoV from 90 participants (median age 40 years, range: 0·9-81 years, 38% female). HCoV-HKU1 was the most common species identified before and after community-wide mitigation. No HCoV-positive samples were identified between May 2020-December 2020. Adults aged ≥50 years had the highest detection of HCoV (11%) among virus-positive samples among all age-groups. Species and sequence data showed diversity between and within HCoV species over the study period. Interpretation: HCoV infections occurred in all congregate homeless shelter site age-groups with the greatest proportion among those aged ≥50 years. Species and sequencing data highlight the complexity of HCoV epidemiology within and between shelters sites. Funding: Gates Ventures, Centers for Disease Control and Prevention, National Institute of Health.

Results from a test-and-treat study for influenza among residents of homeless shelters in King County, WA: A stepped-wedge cluster-randomized trial.

BACKGROUND: Persons experiencing homelessness face increased risk of influenza as overcrowding in congregate shelters can facilitate influenza virus spread. Data regarding on-site influenza testing and antiviral treatment within homeless shelters remain limited. METHODS: We conducted a cluster-randomized stepped-wedge trial of point-of-care molecular influenza testing coupled with antiviral treatment with baloxavir or oseltamivir in residents of 14 homeless shelters in Seattle, WA, USA. Residents ≥3 months with cough or ≥2 acute respiratory illness (ARI) symptoms and onset <7 days were eligible. In control periods, mid-nasal swabs were tested for influenza by reverse transcription polymerase chain reaction (RT-PCR). The intervention period included on-site rapid molecular influenza testing and antiviral treatment for influenza-positives if symptom onset was <48 h. The primary endpoint was monthly influenza virus infections in the control versus intervention periods. Influenza whole genome sequencing was performed to assess transmission and antiviral resistance. RESULTS: During 11/15/2019-4/30/2020 and 11/2/2020-4/30/2021, 1283 ARI encounters from 668 participants were observed. Influenza virus was detected in 51 (4%) specimens using RT-PCR (A = 14; B = 37); 21 influenza virus infections were detected from 269 (8%) intervention-eligible encounters by rapid molecular testing and received antiviral treatment. Thirty-seven percent of ARI-participant encounters reported symptom onset < 48 h. The intervention had no effect on influenza virus transmission (adjusted relative risk 1.73, 95% confidence interval [CI] 0.50-6.00). Of 23 influenza genomes, 86% of A(H1N1)pdm09 and 81% of B/Victoria sequences were closely related. CONCLUSION: Our findings suggest feasibility of influenza test-and-treat strategies in shelters. Additional studies would help discern an intervention effect during periods of increased influenza activity.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing.

BACKGROUND: Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. OBJECTIVE: The IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and non-medical settings. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through April 1, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel made ten diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. CONCLUSIONS: U.S. Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared to nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms, and in symptomatic patients, on timing of testing after symptom onset. In contrast, Ag tests have high specificity, and, in most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared to testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remains the testing method of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

A Risk Prediction Model to Identify Newborns at Risk for Missing Early Childhood Vaccinations.

BACKGROUND: Approximately 30% of US children aged 24 months have not received all recommended vaccines. This study aimed to develop a prediction model to identify newborns at high risk for missing early childhood vaccines. METHODS: A retrospective cohort included 9080 infants born weighing ≥2000 g at an academic medical center between 2008 and 2013. Electronic medical record data were linked to vaccine data from the Washington State Immunization Information System. Risk models were constructed using derivation and validation samples. K-fold cross-validation identified risk factors for model inclusion based on alpha = 0.01. For each patient in the derivation set, the total number of weighted adverse risk factors was calculated and used to establish groups at low, medium, or high risk for undervaccination. Logistic regression evaluated the likelihood of not completing the 7-vaccine series by age 19 months. The final model was tested using the validation sample. RESULTS: Overall, 53.6% failed to complete the 7-vaccine series by 19 months. Six risk factors were identified: race/ethnicity, maternal language, insurance status, birth hospitalization length of stay, medical service, and hepatitis B vaccine receipt. Likelihood of non-completion was greater in the high (77.1%; adjusted odds ratio [AOR] 5.6; 99% confidence interval [CI]: 4.2, 7.4) and medium (52.7%; AOR 1.9; 99% CI: 1.6, 2.2) vs low (38.7%) risk groups in the derivation sample. Similar results were observed in the validation sample. CONCLUSIONS: Our prediction model using information readily available in birth hospitalization records consistently identified newborns at high risk for undervaccination. Early identification of high-risk families could be useful for initiating timely, tailored vaccine interventions.

SARS-CoV-2 RNA positive pediatric organ donors: A case report.

BACKGROUND: Preliminary evidence suggests that non-lung organ donation from resolved, asymptomatic or mildly symptomatic SARS-CoV-2 infected adults may be safe. However, several biological aspects of SARS-CoV-2 infection differ in children and the risk for transmission and outcomes of recipients from pediatric donors with SARS-CoV-2 infection are not well described. METHODS: We report two unvaccinated asymptomatic pediatric non-lung organ deceased donors who tested positive for SARS-CoV-2 RNA by RT-PCR. Donor One unexpectedly had SARS-CoV-2 RNA detected in nasopharyngeal swab and plasma specimens at autopsy despite several negative tests (upper and lower respiratory tract) in the days prior to organ recovery. Donor Two had SARS-CoV- 2 RNA detected in multiple nasopharyngeal swabs but not lower respiratory tract specimens (endotracheal aspirate and bronchoalveolar lavage) during routine surveillance prior to organ recovery and was managed with remdesivir and monoclonal antibodies prior to organ recovery. RESULTS: Two hearts, two livers and four kidneys were successfully transplanted into seven recipients. No donor to recipient transmission of SARS-CoV-2 was observed and graft function of all organs has remained excellent for up to 7 months of followup. CONCLUSIONS: Due to the persistent gap between organ availability and the number of children waiting for transplants, deceased pediatric patients with non-disseminated SARS-CoV-2 infection, isolated to upper and/or lower respiratory tract, should be considered as potential non-lung organ donors.

Trends in Risk Factors and Symptoms Associated With SARS-CoV-2 and Rhinovirus Test Positivity in King County, Washington, June 2020 to July 2022.

Importance: Few US studies have reexamined risk factors for SARS-CoV-2 positivity in the context of widespread vaccination and new variants or considered risk factors for cocirculating endemic viruses, such as rhinovirus. Objectives: To evaluate how risk factors and symptoms associated with SARS-CoV-2 test positivity changed over the course of the pandemic and to compare these with the risk factors associated with rhinovirus test positivity. Design, Setting, and Participants: This case-control study used a test-negative design with multivariable logistic regression to assess associations between SARS-CoV-2 and rhinovirus test positivity and self-reported demographic and symptom variables over a 25-month period. The study was conducted among symptomatic individuals of all ages enrolled in a cross-sectional community surveillance study in King County, Washington, from June 2020 to July 2022. Exposures: Self-reported data for 15 demographic and health behavior variables and 16 symptoms. Main Outcomes and Measures: Reverse transcription-polymerase chain reaction-confirmed SARS-CoV-2 or rhinovirus infection. Results: Analyses included data from 23 498 individuals. The median (IQR) age of participants was 34.33 (22.42-45.08) years, 13 878 (59.06%) were female, 4018 (17.10%) identified as Asian, 654 (2.78%) identified as Black, and 2193 (9.33%) identified as Hispanic. Close contact with an individual with SARS-CoV-2 (adjusted odds ratio [aOR], 3.89; 95% CI, 3.34-4.57) and loss of smell or taste (aOR, 3.49; 95% CI, 2.77-4.41) were the variables most associated with SARS-CoV-2 test positivity, but both attenuated during the Omicron period. Contact with a vaccinated individual with SARS-CoV-2 (aOR, 2.03; 95% CI, 1.56-2.79) was associated with lower odds of testing positive than contact with an unvaccinated individual with SARS-CoV-2 (aOR, 4.04; 95% CI, 2.39-7.23). Sore throat was associated with Omicron infection (aOR, 2.27; 95% CI, 1.68-3.20) but not Delta infection. Vaccine effectiveness for participants fully vaccinated with a booster dose was 93% (95% CI, 73%-100%) for Delta, but not significant for Omicron. Variables associated with rhinovirus test positivity included being younger than 12 years (aOR, 3.92; 95% CI, 3.42-4.51) and experiencing a runny or stuffy nose (aOR, 4.58; 95% CI, 4.07-5.21). Black race, residing in south King County, and households with 5 or more people were significantly associated with both SARS-CoV-2 and rhinovirus test positivity. Conclusions and Relevance: In this case-control study of 23 498 symptomatic individuals, estimated risk factors and symptoms associated with SARS-CoV-2 infection changed over time. There was a shift in reported symptoms between the Delta and Omicron variants as well as reductions in the protection provided by vaccines. Racial and sociodemographic disparities persisted in the third year of SARS-CoV-2 circulation and were also present in rhinovirus infection. Trends in testing behavior and availability may influence these results.

Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Children.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children generally have milder presentations, but severe disease can occur in all ages. MIS-C and persistent post-acute COVID-19 symptoms can be experienced by children with previous infection and emphasize the need for infection prevention. Optimal treatment for COVID-19 is not known, and clinical trials should include children to guide therapy. Vaccines are the best tool at preventing infection and severe outcomes of COVID-19. Children suffered disproportionately during the pandemic not only from SARS-CoV-2 infection but because of disruptions to daily life, access to primary care, and worsening income inequalities.

Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021.

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years† with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.

Human Parainfluenza Virus in Homeless Shelters before and during the COVID-19 Pandemic, Washington, USA.

To determine the epidemiology of human parainfluenza virus in homeless shelters during the COVID-19 pandemic, we analyzed data and sequences from respiratory specimens collected in 23 shelters in Washington, USA, during 2019-2021. Two clusters in children were genetically similar by shelter of origin. Shelter-specific interventions are needed to reduce these infections.

Investigating Health Disparities Associated With Multisystem Inflammatory Syndrome in Children After SARS-CoV-2 Infection.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities. METHODS: This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression. RESULTS: We compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28). CONCLUSIONS: In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.

Analysis of Vaccine Reactions After COVID-19 Vaccine Booster Doses Among Pregnant and Lactating Individuals.

Importance: COVID-19 vaccine boosters or third doses are recommended for adolescents and adults who completed their initial COVID-19 vaccine course more than 5 months prior. Minimal data are available on COVID-19 vaccine booster or third dose reactogenicity among pregnant and lactating individuals. Objective: To describe the reactions to the booster or third dose of the COVID-19 vaccine and vaccine experiences among pregnant and lactating individuals. Design, Setting, and Participants: Beginning in October 2021, a follow-up Research Electronic Data Capture (REDCap) survey regarding a COVID-19 vaccine booster or third dose was sent to 17 504 participants in an ongoing online prospective cohort study on COVID-19 vaccines among pregnant and lactating individuals. A convenience sample of adults enrolled in the online prospective study who were pregnant, lactating, or neither pregnant nor lactating at the time of their booster or third dose was eligible for this follow-up survey; 17 014 (97.2%) completed the follow-up survey. Exposure: Receipt of a booster or third dose of the COVID-19 vaccine. Main Outcomes and Measures: Self-reported vaccine reactions less than 24 hours after the dose. Results: As of April 4, 2022, 17 014 eligible participants (mean [SD] age, 33.3 [3.5] years) responded to the booster or third dose survey; of these, 2009 (11.8%) were pregnant at the time of their booster or third dose, 10 279 (60.4%) were lactating, and 4726 (27.8%) were neither pregnant nor lactating. After a COVID-19 booster or third dose, most individuals (14 074 of 17 005 [82.8%]) reported a local reaction, and 11 542 of 17 005 (67.9%) reported at least 1 systemic symptom. Compared with individuals who were neither pregnant nor lactating, pregnant participants were more likely to report any local reaction to a COVID-19 booster or third dose (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.4; P = .01) but less likely to report any systemic reaction (aOR, 0.7; 95% CI, 0.6-0.8; P < .001). Most pregnant (1961 of 2009 [97.6%]) and lactating (9866 of 10 277 [96.0%]) individuals reported no obstetric or lactation concerns after vaccination. Conclusions and Relevance: This study suggests that COVID-19 vaccine boosters or third doses were well tolerated among pregnant and lactating individuals. Data to evaluate tolerability of boosters or additional doses among pregnant and lactating individuals will be important as they are considered for these populations.