Journal of the Pediatric Infectious Diseases Society

The recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options for mild-to-moderate Covid-19 in high-risk adolescents and adults. In this report we describe patient characteristics, treatment-related process measures and outcomes associated with early Covid-19 therapy in high-risk pediatric patients.

Generally, children and teenagers do not become seriously ill with COVID-19. However, in countries with high rates of coronavirus disease, children with the syndrome COVID-19 associated inflammation syndrome referred to as PIMS-TS have been reported. Similarities noted between SARS-CoV-2 Spike protein sequences and those of other super antigens has prompted the suggestion that this might be the mechanism by SARS-CoV-ST triggers PIMS-TS. It has also been suggested that the D614G variant found more commonly in the US and across European countries may explain why PIMS-TS appears to be common in these countries. Here we analysed viral sequences from 13 paediatric COVID-19 patients of whom five were diagnosed with PIMS-TS. This is the first characterisation of viruses from PIMS-TS patients. In contrast to what has been hypothesised, we found no evidence of unique sequences associated with the viruses from PIMS-TS patients.

ImportanceMultisystem inflammatory syndrome in children (MIS-C) is an uncommon but severe hyperinflammatory illness occurring 2-6 weeks after SARS-CoV-2 infection. Presentation overlaps with other conditions, and risk factors for severe clinical outcomes differ by patient. Characterizing patterns of MIS-C presentation can guide efforts to reduce misclassification, categorize phenotypes, and identify patients at risk for severe outcomes. ObjectiveTo characterize phenotypic clusters of MIS-C and identify clusters with increased clinical severity. DesignWe describe MIS-C phenotypic clusters inferred using latent class analysis (LCA) applied to the largest cohort to date of cases from U.S. national surveillance. Illness onset ranged from February 2020 through December 2022. SettingNational surveillance comprising data from 55 U.S. public health jurisdictions. ParticipantsWe analyzed 9,333 MIS-C cases. Twenty-nine clinical signs and symptoms were selected for clustering after excluding variables with [≥]20% missingness and [≤]10% or [≥]90% prevalence. We excluded 389 cases missing [≥]10 variables and conducted multiple imputation on the remaining 8,944 (96%) cases. Main Outcomes and MeasuresDifferences by cluster in prevalence of each clinical sign and symptom, percentage of cases admitted to the intensive care unit (ICU), length of hospital and ICU stay, mortality, and relative frequency over time. ResultsLCA identified three clusters characterized by 1) frequent respiratory findings primarily affecting older children (n = 713; 8.0% of cases; median age: 12.7 years); 2) frequent cardiac complications and shock (n = 3,359; 37.6%; 10.8 years); and 3) remaining cases (n = 4,872; 54.5%; 6.8 years). Mean duration of hospitalization and proportion of cases resulting in ICU admission or death were higher in the respiratory (7.9 days; 49.5%; 4.6%; respectively) and shock/cardiac clusters (8.7 days; 82.3%; 1.0%; respectively) compared with other cases (5.3 days; 33.0%; 0.06%; respectively). The proportion of cases in the respiratory and shock/cardiac clusters decreased after emergence of the Omicron variant in the United States. Conclusions and RelevanceMIS-C cases clustered into three subgroups with distinct clinical phenotypes, illness severity, and distribution over time. Use of clusters in future studies may support efforts to evaluate surveillance case definitions and help identify groups at highest risk for severe outcomes. Key pointsO_ST_ABSQuestionC_ST_ABSCan phenotypic clusters of multisystem inflammatory syndrome in children (MIS-C) be identified, and are some clusters associated with increased severity? FindingsWe describe clusters inferred using latent class analysis (LCA) on 9,333 MIS-C cases from U.S. national surveillance 2020-2022. LCA identified three clusters characterized by frequent respiratory symptoms, frequent cardiac complications and shock, and remaining clinically milder cases. Mortality and ICU admission were highest in the respiratory and shock/cardiac clusters; prevalence of these two clusters decreased over time. MeaningMIS-C clusters had distinct presentation, illness severity, and distribution over time, highlighting the importance of recognizing the varied presentation of MIS-C.

A retrospective observational cohort study evaluated acute illness predictors of pediatric Long COVID in Jamaica. Poisson regression modeling associated acute univariate symptoms of vomiting, abdominal pain, ageusia, anosmia, fatigue, confusion, brain fog, and multisystem inflammatory syndrome in children (MIS-C); multivariable composite predictors of MIS-C, vomiting, and ageusia. A high incidence in our cohort supports needs for improvements applicable in resource-constrained settings.

ObjectiveWe sought to characterize clinical presentation and healthcare utilization for pediatric COVID-19 in Western Pennsylvania (PA). MethodsWe established and analyzed a registry of pediatric COVID-19 in Western PA that includes cases in patients <22 years of age cared for by the pediatric quaternary medical center in the area and its associated pediatric primary care network from March 11 through August 20, 2020. ResultsOur cohort included 424 pediatric COVID-19 cases (mean age 12.5 years, 47.4% female); 65% reported exposure and 79% presented with symptoms. The most common initial healthcare contact was through telehealth (45%). Most cases were followed as outpatients, but twenty-two patients (4.5%) were hospitalized: 19 with acute COVID-19 disease, and three for multisystem inflammatory syndrome of children (MIS-C). Admitted patients were younger (p<0.001) and more likely to have pre-existing conditions (p<0.001). Black/Hispanic patients were 5.8 times more likely to be hospitalized than white patients (p=0.012). Five patients (1.2%) were admitted to the PICU, including all three MIS-C cases; two required BiPAP and one mechanical ventilation. All patients survived. ConclusionsWe provide a comprehensive snapshot of pediatric COVID-19 disease in an area with low to moderate incidence. In this cohort, COVID-19 was generally a mild disease; however, [~]5% of children were hospitalized. Pediatric patients can be critically ill with this infection, including those presenting with MIS-C.

BackgroundMulti-system inflammatory syndrome in children (MIS-C) represents one of the most severe post-acute sequelae of SARS-CoV-2 infection in children, and there is a critical need to characterize its disease patterns for improved recognition and management. Our objective was to characterize subphenotypes of MIS-C based on presentation, demographics and laboratory parameters. MethodsWe conducted a retrospective cohort study of children with MIS-C from March 1, 2020 - April 30, 2022 and cared for in 8 pediatric medical centers that participate in PEDSnet. We included demographics, symptoms, conditions, laboratory values, medications and outcomes (ICU admission, death), and grouped variables into eight categories according to organ system involvement. We used a heterogeneity-adaptive latent class analysis model to identify three clinically-relevant subphenotypes. We further characterized the sociodemographic and clinical characteristics of each subphenotype, and evaluated their temporal patterns. FindingsWe identified 1186 children hospitalized with MIS-C. The highest proportion of children (44{middle dot}4%) were aged between 5-11 years, with a male predominance (61.0%), and non- Hispanic white ethnicity (40{middle dot}2%). Most (67{middle dot}8%) children did not have a chronic condition. Class 1 represented children with a severe clinical phenotype, with 72{middle dot}5% admitted to the ICU, higher inflammatory markers, hypotension/shock/dehydration, cardiac involvement, acute kidney injury and respiratory involvement. Class 2 represented a moderate presentation, with 4-6 organ systems involved, and some overlapping features with acute COVID-19. Class 3 represented a mild presentation, with fewer organ systems involved, lower CRP, troponin values and less cardiac involvement. Class 1 initially represented 51{middle dot}1% of children early in the pandemic, which decreased to 33{middle dot}9% from the pre-delta period to the omicron period. InterpretationMIS-C has a spectrum of clinical severity, with degree of laboratory abnormalities rather than the number of organ systems involved providing more useful indicators of severity. The proportion of severe/critical MIS-C decreased over time. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and preprint articles from December 2019, to July 2022, for studies published in English that investigated the clinical subphenotypes of MIS-C using the terms "multi-system inflammatory syndrome in children" or "pediatric inflammatory multisystem syndrome" and "phenotypes". Most previous research described the symptoms, clinical characteristics and risk factors associated with MIS-C and how these differ from acute COVID-19, Kawasaki Disease and Toxic Shock Syndrome. One single-center study of 63 patients conducted in 2020 divided patients into Kawasaki and non-Kawasaki disease subphenotypes. Another CDC study evaluated 3 subclasses of MIS-C in 570 children, with one class representing the highest number of organ systems, a second class with predominant respiratory system involvement, and a third class with features overlapping with Kawasaki Disease. However, this study evaluated cases from March to July 2020, during the early phase of the pandemic when misclassification of cases as Kawasaki disease or acute COVID-19 may have occurred. Therefore, it is not known from the existing literature whether the presentation of MIS-C has changed with newer variants such as delta and omicron. Added value of this studyPEDSnet provides one of the largest MIS-C cohorts described so far, providing sufficient power for detailed analyses on MIS-C subphenotypes. Our analyses span the entire length of the pandemic, including the more recent omicron wave, and provide an update on the presentations of MIS-C and its temporal dynamics. We found that children have a spectrum of illness that can be characterized as mild (lower inflammatory markers, fewer organ systems involved), moderate (4-6 organ involvement with clinical overlap with acute COVID-19) and severe (higher inflammatory markers, critically ill, more likely to have cardiac involvement, with hypotension/shock and need for vasopressors). Implications of all the available evidenceThese results provide an update to the subphenotypes of MIS-C including the more recent delta and omicron periods and aid in the understanding of the various presentations of MIS-C. These and other findings provide a useful framework for clinicians in the recognition of MIS-C, identify factors associated with children at risk for increased severity, including the importance of laboratory parameters, for risk stratification, and to facilitate early evaluation, diagnosis and treatment.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition associated with pediatric SARS-CoV-2 infection. While COVID-19 vaccines prevent infection and reduce severity, less conclusive evidence exists regarding their role in preventing MIS-C during breakthrough infections. This systematic review assessed the impact of SARS-CoV-2 vaccination on MIS-C risk during breakthrough infection. Cross-sectional studies, surveillance studies, and cohort studies were included. Of the 944 studies identified, 6 were included. A significant protective effect was seen in patients who received two doses of SARS-CoV-2 vaccination after exclusion of a biased sample (d= 0.71 [95% CI 0.07 to 1.35; p=0.03]). A trend towards a protective effect was seen after one dose of vaccination, but this effect was not statistically significant. Current literature supports a protective effect of two doses of SARS-CoV-2 vaccination against development of MIS-C in breakthrough COVID-19. The evidence supports clinician advocacy for continued vaccination of children against SARS-CoV-2.

The impact of post-acute sequelae of SARS-CoV-2 infection (PASC) in children is underrecognized. We developed an EHR-based algorithm across eight pediatric institutions to identify children with COVID-19 based on serology testing from 3/2020 through 4/2022 who had not been identified by PCR. Overall, serology tests were used 100-fold less than PCR. Seroprevalence of IgG anti-nucleocapsid antibodies remained stable, while rates of positive IgG anti-spike antibodies increased in teenagers after COVID-19 vaccine approval. Through data harmonization and after excluding 1,410 serology test results that may have been influenced by vaccines, we identified 2,714 children that were COVID-19 positive exclusively by serology. These patients were frequently tested as inpatients (24% vs. 2%), had chronic conditions more frequently (37% vs 24%), and a MIS-C diagnosis (23% vs. <1%) compared with PCR-positive children. Identification of children that could have been paucisymptomatic, not tested, or missed is critical to define the burden of PASC in children.

The International PANS Registry (IPR) is the first centralized, epidemiologic database of children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and PANS-like features and their siblings. PANS is a relatively new umbrella syndrome that lacks diagnostic biomarkers and is characterized by a set of working criteria. The failure to find a diagnostic biomarker is likely due to underpowered studies and inherent biological heterogeneity within PANS. Until the IPR was established, a critical barrier to large-scale longitudinal studies had been the absence of a large-scale epidemiologic study and a centralized database of children with PANS and PANS-like features. The IPR was created to serve as a translational health tool to accelerate research on the broad spectrum of complex pediatric neuroimmune conditions with the long-term goal of enabling a paradigm shift in this field from symptom-based evaluation and treatment towards biology-based diagnoses, treatments, screening, and surveillance. To date, the IPR has registered 1,666 families (3,247 children) and is the largest database in the world that gathers in-depth information on children with PANS and PANS-like features and their siblings. Enrollment in the IPR is open and ongoing; longitudinal follow up is planned. Participating families enroll their children with PANS and PANS-like features and their healthy siblings in the IPR via an online survey platform. The selection criteria for IPR enrollment are intentionally less restrictive than the current working criteria for PANS to generate a large recruitment pool and enable study of the broad spectrum of PANS-like conditions. The IPR is designed to enable ancillary study recruitment based on detailed selection criteria and to grow and expand in scope in the future. The IPR team is committed to data sharing and invites collaborators who will leverage existing data from the IPR database and extend knowledge in an area beyond the original scope of the IPR.

The evolution of SARS-CoV2 virus has led to the emergence of variants of concern (VOC). Children, particularly <12 years old not yet eligible for vaccines, continue to be important reservoirs of SARS-CoV-2 yet VOC prevalence data in this population is lacking. We report data from a genomic surveillance program that includes 9 U.S. childrens hospitals. Analysis of SARS-CoV-2 genomes from 2119 patients <19 years old between 03/20 to 04/21 identified 252 VOCs and 560 VOC signature mutations, most from 10/20 onwards. From 02/21 to 04/21, B.1.1.7 prevalence increased from 3.85% to 72.22% corresponding with the decline of B.1.429/B.1.427 from 51.82% to 16.67% at one institution. 71.74% of the VOC signature mutations detected were in children <12 years old, including 33 cases of B.1.1.7 and 119 of B.1.429/B.1.427. There continues to be a need for ongoing genomic surveillance, particularly among young children who will be the last groups to be vaccinated.

Using electronic health record data combined with primary chart review, we identified 7 children across 8 pediatric medical centers with a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) who were managed as outpatients. These findings should prompt a discussion about modifying the case definition to allow for such a possibility.

Kawasaki disease (KD) is an acute pediatric vasculitis characterized by dysregulated host immune responses and risk of coronary artery injury. Although a two-transcript IFI27-MCEMP1 axis has been clinically validated to distinguish KD from other febrile illnesses, the long noncoding RNA (lncRNA) context of this interferon-myeloid imbalance remains incompletely understood. We evaluated whether peripheral blood mononuclear cell (PBMC)-derived lncRNAs are altered in KD and associated with the interferon and myeloid components of the IFI27-MCEMP1 transcriptomic axis. Children younger than 8 years with suspected KD were prospectively enrolled at the Children's Hospital of Fudan University from 2024 to 2025. The newly enrolled cohort included 55 children with KD and 48 febrile controls. For integrated immune-transcript association analyses, these data were combined with two previously characterized same-site cohorts, yielding 188 children with KD and 175 febrile controls. Expression of IFI27, MCEMP1, CHROMR, MALAT1, and NEAT1 was measured by reverse transcription quantitative PCR and normalized to GAPDH using {Delta}Ct values. In the newly enrolled cohort, the IFI27-MCEMP1 axis reproduced discrimination between KD and febrile controls, with an area under the receiver operating characteristic curve of 0.88; performance was similar in the integrated cohort, with an area under the curve of 0.89. In PBMC lncRNA analyses, CHROMR and MALAT1 {Delta}Ct values were significantly higher in KD than in febrile controls, indicating lower relative expression, whereas NEAT1 did not show a significant KD-specific differential-expression signal. CHROMR showed the strongest association with the IFI27 interferon-associated component, while MALAT1 showed weaker but directionally informative associations with both IFI27 and MCEMP1, including an inverse association with MCEMP1. These findings support an lncRNA-associated interferon-myeloid immune architecture in KD, marked by coordinated attenuation of IFI27, CHROMR, and MALAT1 together with increased MCEMP1. This PBMC RNA pattern provides a biologically interpretable framework for KD immune dysregulation and generates testable hypotheses regarding RNA-regulatory programs in KD vasculitis.

As the pandemic enters its fifth month, information regarding COVID-19 in children is rapidly evolving. Here, we explore clinical features and SARS-CoV-2 genetic variation in children presenting with COVID-19. We observed diverse clinical presentations and identified association between disease severity, viral load and age. SARS-CoV-2 genomes from the patients showed limited number of variations and an evolutionary rate comparable to other RNA viruses. We did not identify correlation between disease severity and viral genetic variations. Epidemiological investigation revealed multiple introductions of virus into Southern California.

ObjectivesEnterovirus (EV) and parechovirus (PeV) meningitis are significant causes of illness in febrile infants. The clinical significance of detecting EV/PeV in the CSF, particularly in the absence of pleocytosis and neurological symptoms, remains uncertain in this age group. We aimed to characterise the relationship between clinical features, systemic neuroinflammatory and immune responses, and CSF pleocytosis in infants with EV/PeV meningitis. MethodsProspective multicentre observational cohort study of febrile infants <90 days old undergoing CSF testing for infection. Infants were recruited as part of the Febrile Infant Diagnostic Assessment and Outcome (FIDO) Study from 35 Paediatric Emergency Research in the UK and Ireland (PERUKI) sites from 6th July 2022 to 31st August 2023 (NCT05259683). Plasma proteomic profiling of 724 inflammation and neurology-related proteins was performed using Olink technology and compared with clinical and laboratory data. Results603 febrile infants were included, with 21/603 (3{middle dot}5%) PeV, and 173/197 (28.7%) EV meningitis cases. Lymphopenia was significantly more common in infants without pleocytosis, 62/101 (63.9%), than those with pleocytosis 7/54 (16.7%). No significant differences in clinical symptoms or timing of presentation were observed with differing CSF WBC counts. Proteomic analysis (n=131) revealed that infants without pleocytosis exhibited elevated inflammatory cytokine responses and enrichment of pathways related to apoptosis and CNS involvement. In contrast, those with pleocytosis showed muted cytokine responses. ConclusionsThe absence of CSF pleocytosis in EV and PeV meningitis may result from systemic lymphocyte depletion, potentially mediated by cytokine-driven apoptosis. Our findings do not support the hypothesis that the lack of pleocytosis is primarily attributable to early presentation or to incidental detection of viral RNA due to viremia in infants.

BackgroundWith the rise of the COVID-19 pandemic, a new severe life-threatening inflammatory syndrome has been reported in some pediatric populations. Global attention was shifted towards the syndrome termed multisystem inflammatory syndrome in children (MIS-C), with new case reports flooding in. ObjectivesThe aim of this scoping review is to summarize the existing reports on MIS-C and focus on the demographics, diagnosis, clinical presentation, laboratory investigations, imaging studies, treatment, and patient outcomes. MethodsWe conducted a systemic search using LitCovid and MEDLINE electronic databases. We screened citations, titles and abstracts, then reviewed potentially relevant articles in full. After data extraction, we reported our final data under subheadings of demographics, diagnosis, clinical presentation, laboratory investigations, imaging studies, treatment, and patient outcomes. ResultsOur search strategy yielded 42 original studies reporting 674 pediatric patients fitting the case definition of MIS-C. The studies included 21 case reports, 16 case series and 5 cohort studies. The most common reported symptom of MIS-C was fever (98%). Gastrointestinal symptoms were common (N=557, 83%). Interleukin-6 (IL-6) levels were measured in 125 patients and was elevated in 94 % (N=117). Echocardiography detected coronary artery lesions in 100 patients. Prophylactic and/or therapeutic heparin was required in 34% (N=227) of patients. The most commonly administered treatment modality targeting MIS-C was intravenous immunoglobulin (IVIG) (N=490). Corticosteroids (N=347) and aspirin (N=112) were also integral parts of the treatment regimens. Biologic therapy was integrated into the treatment regimen for 116 patients. Intensive care unit (ICU) admission was alarming (N=478, 71%). 9 fatalities were recorded due to MIS-C ConclusionsWe believe MIS-C bears pathophysiological resemblance to the well-known Kawasaki disease but with some key differences highlighted. Understanding those differences will aid our management plan for such patients.

ObjectivesPeriodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common autoinflammatory disorder of childhood, characterized by recurrent febrile episodes driven by dysregulated innate immune activation. Although genetic susceptibility contributes to disease risk, environmental modifiers remain poorly defined. Vaccinations may induce long-lasting modulation of innate immune responses and influence PFAPA incidence. We aimed to assess whether childhood vaccinations, including Bacillus Calmette-Guerin (BCG), are associated with PFAPA risk in a large national cohort. MethodsWe conducted a matched case-control study using electronic health records from a national healthcare provider in Israel. Children diagnosed with PFAPA were matched to children without PFAPA by age, sex, socioeconomic status, ethnic sector, and enrolment year. Vaccination history was obtained from the electronic immunization registry. A systematic screen of associations was performed across all recorded childhood vaccines, followed by adjusted conditional logistic regression models. Prior laboratory test results were analysed to characterize the immune profile. ResultsThe study included 1,641 PFAPA cases and 32,820 matched controls. Among all vaccines examined, prior Bacillus Calmette-Guerin (BCG) vaccination, received by 401 children (3 cases, 398 controls), showed the strongest association with reduced PFAPA risk (adjusted odds ratio 0.15, 95% confidence interval [CI] 0.05-0.46, p=0.001). Associations with other vaccines were heterogeneous and of smaller magnitude. PFAPA cases demonstrated a myeloid-skewed inflammatory profile prior to diagnosis, including elevated C-reactive protein, neutrophilia, increased neutrophil-to-lymphocyte ratio, and relative lymphopenia. ConclusionsIn this nationwide study, prior BCG vaccination emerged from a systematic screen as strongly associated with reduced PFAPA risk, supporting a role for immune programming in susceptibility to childhood autoinflammatory disease.

Inflammation following neonatal infection is a dominant cause of childhood hydrocephalus in the developing world. Understanding this complex inflammatory response is critical for the development of preventive therapies. In 100 African hydrocephalic infants [&le;]3 months of age, with and without a history of infection, we elucidated the biological pathways that account for this inflammatory response. We integrated proteomics and RNA sequencing in cerebrospinal fluid, identifying gene pathways involving neutrophil, interleukin (4, 12, and 13) and interferon activity associated with this condition. These findings are required to develop strategies to reduce the risk of hydrocephalus during treatment of infection.

Direct comparisons of pediatric hospitalizations for acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) can inform health system planning. While there were more hospitalizations and deaths from acute COVID-19 amongst Canadian children between March 2020-May 2021, MIS-C cases were more severe, requiring more intensive care and vasopressor support.

Pediatric SARS-CoV-2 infection results in clinical presentations ranging from asymptomatic/mild infection to severe pulmonary COVID-19, to Multisystem Inflammatory Syndrome in Children (MIS-C), characterized by hyperinflammation and multi-organ involvement. While various aspects of antibody responses to pediatric SARS-CoV-2 infection manifestations have been reported, parallel studies of antibody responses to viral and self-antigens are understudied. We tested whether clinical presentations of increasing severity corresponded to different antiviral antibody and autoantibody signatures. Using custom arrays, we found that, relative to uninfected subjects, all SARS-CoV-2 infection manifestations were associated with increased autoantibody production, suggesting pediatric SARS-CoV-2 infection as a risk factor for autoimmune complications. Subtle differences were seen in autoantibody patterns among infection groups, with some autoantibodies more associated with mild manifestations and others with severe ones. When we compared MIS-C and severe COVID-19 subjects, we found differences in IgG (mostly IgG1) abundance but not in Fc-mediated effector functions. Thus, MIS-C may be associated with abnormal antibody function, suggesting that this syndrome, and perhaps other post-acute sequelae of SARS-CoV-2 infection, may be associated with antibody dysfunction. Our study shows that the antibody repertoire varies with clinical presentation of SARS-CoV-2 in children and its analysis may help understand long COVID pathogenesis. ImpactOur study shows that the antibody repertoire varies with the clinical presentation of SARS-CoV-2 in children, which has implications for understanding long COVID pathogenesis.

Respiratory syncytial virus (RSV) infections and hospitalization have surged sharply among young children. Here we test how the seasonal patterns of RSV infections in 2022 compared with those from other COVID-19 pandemic and pre-pandemic years. For this purpose, we analyzed a nation-wide and real-time database of electronic health records of 56 million patients across 50 states in the US. The monthly incidence rate of first-time RSV infection in young children (<5 years of age) and very young children (<1 year of age) followed a seasonal pattern from 2010 to 2019 with increases during the autumn, peaking in winter, subsiding in spring and summer. This seasonal pattern was significantly disrupted during the COVID-19 pandemic. In 2020, the incidence rate of RSV infections was remarkably low throughout the year. In 2021, the RSV season expanded to 9 months starting in the early summer and peaking in October. In 2022, RSV infections started to rise in May and were significantly higher than in previous years reaching a historically highest incidence rate in November 2022. There were significant racial and ethnic disparities in the peak RSV infection rate during 2010-2021 and the disparities further exacerbated in 2022 with peak incidence rate in black and Hispanic children 2-3 times that in white children. Among RSV-infected children in 2022, 19.2% had prior documented COVID-19 infection, significantly higher than the 9.7% among uninfected children, suggesting that prior COVID-19 could be a risk factor for RSV infection or that there are common risk factors for both viral infections. Our study calls for continuous monitoring of RSV infection in young children alongside its clinical outcomes and for future work to assess potential COVID-19 related risk factors.