Shifting Epidemiology and Severity of Respiratory Syncytial Virus in Children During the COVID-19 Pandemic.

This cohort study examined changes in RSV age distribution and disease severity in Colorado children after the COVID-19 pandemic.

Respiratory Syncytial Virus, Influenza, and Coronavirus Disease 2019 Hospitalizations in Children in Colorado During the 2021-2022 Respiratory Virus Season.

OBJECTIVE: To compare demographic characteristics, clinical features, and outcomes of children hospitalized with respiratory syncytial virus (RSV), influenza, or severe acute respiratory syndrome coronavirus 2 during their cocirculation 2021-2022 respiratory virus season. METHODS: We conducted a retrospective cohort study using Colorado's hospital respiratory surveillance data comparing coronavirus disease 2019 (COVID-19)-, influenza-, and RSV-hospitalized cases < 18 years of age admitted and undergoing standardized molecular testing between October 1, 2021, and April 30, 2022. Multivariable log-binomial regression modeling evaluated associations between pathogen type and diagnosis, intensive care unit admission, hospital length of stay, and highest level of respiratory support received. RESULTS: Among 847 hospitalized cases, 490 (57.9%) were RSV associated, 306 (36.1%) were COVID-19 associated, and 51 (6%) were influenza associated. Most RSV cases were <4 years of age (92.9%), whereas influenza hospitalizations were observed in older children. RSV cases were more likely to require oxygen support higher than nasal cannula compared with COVID-19 and influenza cases (P < .0001), although COVID-19 cases were more likely to require invasive mechanical ventilation than influenza and RSV cases (P < .0001). Using multivariable log-binomial regression analyses, compared with children with COVID-19, the risk of intensive care unit admission was highest among children with influenza (relative risk, 1.97; 95% CI, 1.22-3.19), whereas the risk of pneumonia, bronchiolitis, longer hospital length of stay, and need for oxygen were more likely among children with RSV. CONCLUSIONS: In a season with respiratory pathogen cocirculation, children were hospitalized most commonly for RSV, were younger, and required higher oxygen support and non-invasive ventilation compared with children with influenza and COVID-19.

COVID-19 and Acute Otitis Media in Children: A Case Series.

BACKGROUND: The association of SARS-CoV-2 with acute otitis media (AOM) in children is poorly understood. METHODS: Cases were identified as a subpopulation within the NO TEARS prospective AOM study in Denver, CO from March to December 2020. Children enrolled were 6 to 35 months of age with uncomplicated AOM; those with AOM and SARS-CoV-2 were included. Data was obtained from electronic medical records and research case report forms. RESULTS: A total of 108 patients enrolled in the NO TEARS study from May 2019 through December 2020 (all subsequently tested for SARS CoV-2). During the COVID-19 pandemic study period (March-December 2020), 16 patients enrolled, and 7 (43.6%) were identified with AOM/COVID-19 co-infection. Fever was present in 3 of 7 children (29%). Four children (57%) attended daycare. Only 2 children (29%) had SARS CoV-2 testing as part of their clinical workup. Mean AOM-SOS© scores were similar among SARS CoV-2 positive and negative patients with no statistical significance with two-sided t-tests: 13.6 (±4.5) versus 14.2 (±4.9) at enrollment, 1.4 (±1.8) versus 4.2 (±4.9) on Day 5, and 0.6 (±0.9) versus 2.5 (±6.1) on Day 14. Among the 7 cases, no child had an AOM treatment failure or recurrence within 3 to 14 or 15 to 30 days respectively. Of the 6 patients with completed bacterial and viral testing, a bacterial pathogen was identified in all 6, and a viral pathogen in 3 (50%). CONCLUSIONS: COVID-19 and AOM can co-exist. Providers should maintain a high index of suspicion for COVID-19 even in patients with clinical AOM and should not use a diagnosis of AOM to exclude COVID-19.

SARS-CoV-2 Seroprevalence Compared with Confirmed COVID-19 Cases among Children, Colorado, USA, May-July 2021.

To compare SARS-CoV-2 antibody seroprevalence among children with seropositive confirmed COVID-19 case counts (case ascertainment by molecular amplification) in Colorado, USA, we conducted a cross-sectional serosurvey during May-July 2021. For a convenience sample of 829 Colorado children, SARS-CoV-2 seroprevalence was 36.7%, compared with prevalence of 6.5% according to individually matched COVID-19 test results reported to public health. Compared with non-Hispanic White children, seroprevalence was higher among Hispanic, non-Hispanic Black, and non-Hispanic other race children, and case ascertainment was significantly lower among Hispanic and non-Hispanic Black children. This serosurvey accurately estimated SARS-CoV-2 prevalence among children compared with confirmed COVID-19 case counts and revealed substantial racial/ethnic disparities in infections and case ascertainment. Continued efforts to address racial and ethnic differences in disease burden and to overcome potential barriers to case ascertainment, including access to testing, may help mitigate these ongoing disparities.

Acute Liver Failure in a Child With Adenovirus Detected by PCR in the Explanted Liver.

As of June 15, 2022, the Centers for Disease Control and Prevention has reported 296 pediatric patients under investigation for hepatitis of unknown etiology in the United States; the World Health Organization has reported 650 probable cases worldwide. One of the leading hypotheses for this cluster of cases is adenovirus, a virus that commonly causes respiratory or gastrointestinal symptoms in healthy children but rarely causes severe hepatitis or acute liver failure in immunocompetent children. The other leading hypothesis is that prior infection with SARS-CoV-2 may predispose children to developing liver injury from a normally innocuous agent. We describe a case of a previously healthy child presenting with acute liver failure who had detectable adenovirus DNA in his stool, whole blood, and in liver explant tissue, suggesting adenovirus as the likely etiology for the liver failure. He had no evidence of prior or current SARS-CoV-2 infection, nor had he received COVID vaccination, suggesting that SARS-CoV-2 did not play a role. Additionally, we report on the ability to provide rapid evaluation of a living donor within 72 hours and successfully perform a lifesaving, left-lobe, living donor liver transplant.

Kathryn V. Holmes: A Career of Contributions to the Coronavirus Field.

Over the past two years, scientific research has moved at an unprecedented rate in response to the COVID-19 pandemic. The rapid development of effective vaccines and therapeutics would not have been possible without extensive background knowledge on coronaviruses developed over decades by researchers, including Kathryn (Kay) Holmes. Kay's research team discovered the first coronavirus receptors for mouse hepatitis virus and human coronavirus 229E and contributed a wealth of information on coronaviral spike glycoproteins and receptor interactions that are critical determinants of host and tissue specificity. She collaborated with several research laboratories to contribute knowledge in additional areas, including coronaviral pathogenesis, epidemiology, and evolution. Throughout her career, Kay was an extremely dedicated and thoughtful mentor to numerous graduate students and post-doctoral fellows. This article provides a review of her contributions to the coronavirus field and her exemplary mentoring.

Epidemiological and Clinical Features of Kawasaki Disease During the COVID-19 Pandemic in the United States.

Importance: Public health measures implemented during the COVID-19 pandemic had widespread effects on population behaviors, transmission of infectious diseases, and exposures to environmental pollutants. This provided an opportunity to study how these factors potentially influenced the incidence of Kawasaki disease (KD), a self-limited pediatric vasculitis of unknown etiology. Objectives: To examine the change in KD incidence across the United States and evaluate whether public health measures affected the prevalence of KD. Design, Setting, and Participants: This multicenter cohort study included consecutive, unselected patients with KD who were diagnosed between January 1, 2018, and December 31, 2020 (multicenter cohort with 28 pediatric centers), and a detailed analysis of patients with KD who were diagnosed between January 1, 2002, and November 15, 2021 (Rady Children's Hospital San Diego [RCHSD]). Main Outcomes and Measures: For the multicenter cohort, the date of fever onset for each patient with KD was collected. For RCHSD, detailed demographic and clinical data as well as publicly available, anonymized mobile phone data and median household income by census block group were collected. The study hypothesis was that public health measures undertaken during the pandemic would reduce exposure to the airborne trigger(s) of KD and that communities with high shelter-in-place compliance would experience the greatest decrease in KD incidence. Results: A total of 2461 KD cases were included in the multicenter study (2018: 894; 2019: 905; 2020: 646), and 1461 cases (median [IQR] age, 2.8 years [1.4-4.9 years]; 900 [61.6%] males; 220 [15.1%] Asian, 512 [35.0%] Hispanic, and 338 [23.1%] White children) from RCHSD between 2002 and 2021 were also included. The 28.2% decline in KD cases nationally during 2020 (646 cases) compared with 2018 (894 cases) and 2019 (905 cases) was uneven across the United States. For RCHSD, there was a disproportionate decline in KD cases in 2020 to 2021 compared with the mean (SD) number of cases in earlier years for children aged 1 to 5 years (22 vs 44.9 [9.9]; P = .02), male children (21 vs 47.6 [10.0]; P = .01), and Asian children (4 vs 11.8 [4.4]; P = .046). Mobility data did not suggest that shelter-in-place measures were associated with the number of KD cases. Clinical features including strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation were decreased during 2020 compared with the baseline period (strawberry tongue: 39% vs 63%; P = .04; enlarged lymph node: 21% vs 32%; P = .09; periungual desquamation: 47% vs 58%; P = .16). School closures, masking mandates, decreased ambient pollution, and decreased circulation of respiratory viruses all overlapped to different extents with the period of decreased KD cases. KD in San Diego rebounded in the spring of 2021, coincident with lifting of mask mandates. Conclusions and Relevance: In this study of epidemiological and clinical features of KD during the COVID-19 pandemic in the United States, KD cases fell and remained low during the period of masking and school closure. Mobility data indicated that differential intensity of sheltering in place was not associated with KD incidence. These findings suggest that social behavior is associated with exposure to the agent(s) that trigger KD and are consistent with a respiratory portal of entry for the agent(s).

Impact of the lockdown period due to the COVID-19 pandemic in patients with inflammatory bowel disease Impacto del confinamiento debido a la pandemia por COVID-19 en pacientes con enfermedad inflamatoria intestinal

Introduction The lockdown period due to the coronavirus disease 2019 (COVID-19) in Spain probably had a significant emotional impact on chronic patients and hence on those who are suffering from inflammatory bowel disease (IBD) due to their high risk of emotional disorders. The aim of this study was to learn how COVID-19 influenced patients suffering from IBD during the quarantine period, focusing in particular on psychological distress through the Perceived Stress Scale-10 (PSS-10) and also the impact of the pandemic on therapeutic adherence using the Visual Analogue Scale (VAS). Patients and methods A prospective, single-centre and analytical observational study was carried out in the IBD unit in August 2020. Patients were contacted and interviewed by phone. A descriptive analysis was carried out and subsequently the factors associated with the loss of therapeutic adherence and higher-moderate levels of stress were analyzed through logistic regression multivariate analyses. Results A total of 426 patients were included with a median PSS-10 score of 12 (10–16). A higher level of stress was reported by those who were not married, women and those who experienced an increase in IBD-related symptoms. Adherence to treatment was not associated with stress based on the PSS-10 questionnaire. Conclusions Although the lockdown period due to the COVID-19 pandemic has probably had a significant emotional impact on Spaniards with IBD, IBD patients in general had lower PSS-10 scores.

SARS-CoV-2 and Acute Otitis Media in Children: A Case Series

Background Reports in adults with COVID-19 and acute otitis media (AOM) show that severe symptoms and hearing loss may be more common than with the clinical presentation of typical AOM. However, the association of SARS-CoV-2 with AOM in children is poorly understood. Methods Cases were identified as a subpopulation enrolled in the NOTEARS prospective AOM study in Denver, CO from March-December 2020. Children enrolled were 6-35 months of age with uncomplicated AOM and prescribed amoxicillin. Children diagnosed with AOM and SARS-CoV-2, detected by polymerase chain reaction assay, were included in the case series. Data was obtained from electronic medical records and research case report forms. Patients completed surveys at enrollment and 5, 14 and 30 days after enrollment that included the Acute Otitis Media Severity of Symptoms (AOM-SOS©) scale. All patients had nasopharyngeal otopathogen testing completed. Results A total of 108 patients had been enrolled through December 2020 (all of whom were subsequently tested for SARS CoV-2). During the study period for this case series, 16 patients were enrolled, and 7 (43.6%) were identified with AOM/SARS-CoV-2 co-infection. Among these 7 patients, fever was present in 3 children (29%). Four children (57%) attended daycare. Only 2 children (29%) had testing for SARS CoV-2 as part of their clinical workup. Mean AOM-SOS© scores were similar among the SARS CoV-2 positive and negative patients with no statistical significance noted with two-sided t-tests: 13.6 (± 4.5) vs 14.2 (± 4.9) at enrollment, 1.4 (± 1.8) vs 4.2 (±4.9) on Day 5, and 0.6 (± 0.9) vs. 2.5 (±6.1) on Day 14 (Table 1). Among the 7 patients, no child had an AOM treatment failure or recurrence. Of the 6 patients in whom bacterial and viral testing have been completed, a bacterial otopathogen was identified in 6 (100%), and a viral pathogen in 3 (50%) children (Table 2). Table 1. Clinical features of children with concurrent SARS-CoV-2 and AOM Table 2. Laboratory findings of children with concurrent SARS-CoV-2 and AOM. Conclusion SARS-CoV-2 can occur in children with AOM. It is important that providers maintain a high index of suspicion for COVID-19 even in patients with clinical evidence of AOM, particularly to ensure families are appropriately advised on isolation and quarantine requirements. AOM with SARS-CoV-2 does not appear to be more severe than AOM without SARS-CoV-2. Disclosures Samuel R. Dominguez, MD, PhD, BioFire Diagnostics (Consultant, Research Grant or Support)DiaSorin Molecular (Consultant)Pfizer (Grant/Research Support) Samuel R. Dominguez, MD, PhD, BioFire (Individual(s) Involved: Self): Consultant, Research Grant or Support;DiaSorin Molecular (Individual(s) Involved: Self): Consultant;Pfizer (Individual(s) Involved: Self): Grant/Research Support

Persistence of SARS-CoV-2 Iinfection in Immunocompromised Children

Background The temporal dynamics of SARS-CoV-2 infectivity in immunocompromised children (IC) are unknown but may have important infection control implications. We evaluated SARS-CoV-2 viral persistence and assessed factors associated with viral persistence and cycle threshold (CT) values as a surrogate of viral load for IC. Methods We conducted a retrospective cohort study of SARS-CoV-2-positive IC at a large quaternary pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary or secondary/acquired immunodeficiencies due to comorbidities or immunosuppressive treatment. The primary outcome was time to first-of-two consecutively negative SARS-CoV-2 PCR tests ≥ 24 hours apart. Polymerase chain reaction (PCR) testing of sequential patient samples was conducted using the Centers for Disease Control 2019-nCoV Real-Time RT-PCR Diagnostic Panel (CDC assay). Chi-square, Fisher exact, and Wilcoxon tests were used to compare demographic and clinical characteristics. Kaplan-Meier curve median event times and log-rank tests were used to compare outcomes. Subjects without 2 consecutive negative tests censored at the last test. Analyses were conducted using SAS v 9.4. Results Ninety-one children met inclusion criteria, and 67 children had more than 1 test (Figure 1). Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% of children were white, and 43% were Latinx. Most (67%) were tested in outpatient settings, and 58% of children were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no difference in duration of positivity with specific diagnoses, degree of lymphopenia, or symptomatic vs asymptomatic illness. Five of 7 (71%) children with samples available for repeat testing had initial CT values < 30, indicating a moderate to high viral load, and of these, 4 (57%) had repeat testing 21 to 30 days later with CT values < 30 (Figure 2), suggesting persistence of moderate to high viral loads. Figure 1. Plot of immunocompromised children in cohort with positive SARS CoV2 PCR and subsequent testing (n = 67). Timelines of immunocompromised children in cohort with positive SARS CoV2 PCR and subsequent testing, grouped by immunocompromising condition. Each line represents an individual patient. Positive results are shown in light grey, negative results are shown in black. Figure 2. Plot of CT values from SARS-CoV-2 PCR testing over time among children with sequential samples available for retesting (n = 7) Plot of CT values (y axis) from SARS-CoV-2 PCR testing on the CDC assay over time (x axis) in days from initial positive test. Repeated testing which yielded a negative result on the CDC assay or intermittent negative results on clinical testing represented as CT value of 40. Each line represents a unique patient. Conclusion The median duration of viral persistence among IC with SARS-CoV-2 infection was 6 weeks, with no significant difference in immunocompromised diagnoses or clinical presentation, with over half of children with testing on the same platform having moderate to high viral loads after 3 weeks, suggesting potential transmission risk. Disclosures Samuel R. Dominguez, MD, PhD, BioFire Diagnostics (Consultant, Research Grant or Support)DiaSorin Molecular (Consultant)Pfizer (Grant/Research Support) Samuel R. Dominguez, MD, PhD, BioFire (Individual(s) Involved: Self): Consultant, Research Grant or Support;DiaSorin Molecular (Individual(s) Involved: Self): Consultant;Pfizer (Individual(s) Involved: Self): Grant/Research Support Suchitra Rao, MBBS, MSCS, BioFire (Research Grant or Support)

SARS-CoV-2 persistence in immunocompromised children.

OBJECTIVES: We evaluated the length of time immunocompromised children (ICC) remain positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified factors associated with viral persistence, and determined cycle threshold (CT ) values of children with viral persistence as a surrogate of viral load. METHODS: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020 to March 2021. Immunocompromised status was defined as primary, secondary, or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first of two consecutive negative SARS-CoV-2 polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV real-time reverse transcriptase (RT)-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank tests were used to compare outcomes between groups. RESULTS: Ninety-one children met inclusion criteria. Median age was 15.5 years (interquartile range [IQR] 8-18), 64% were male, 58% were White, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0-55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had more than one sample available for repeat testing, and five of seven (71%) children had initial CT values of <30 (moderate to high viral load); four children had CT values of <30, 3-4 weeks later, suggesting persistent moderate to high viral loads. CONCLUSIONS: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.

Impact of the lockdown period due to the COVID-19 pandemic in patients with inflammatory bowel disease.

INTRODUCTION: The lockdown period due to the coronavirus disease 2019 (COVID-19) in Spain probably had a significant emotional impact on chronic patients and hence on those who are suffering from inflammatory bowel disease (IBD) due to their high risk of emotional disorders. The aim of this study was to learn how COVID-19 influenced patients suffering from IBD during the quarantine period, focusing in particular on psychological distress through the Perceived Stress Scale-10 (PSS-10) and also the impact of the pandemic on therapeutic adherence using the Visual Analogue Scale (VAS). PATIENTS AND METHODS: A prospective, single-centre and analytical observational study was carried out in the IBD unit in August 2020. Patients were contacted and interviewed by phone. A descriptive analysis was carried out and subsequently the factors associated with the loss of therapeutic adherence and higher-moderate levels of stress were analyzed through logistic regression multivariate analyses. RESULTS: A total of 426 patients were included with a median PSS-10 score of 12 (10-16). A higher level of stress was reported by those who were not married, women and those who experienced an increase in IBD-related symptoms. Adherence to treatment was not associated with stress based on the PSS-10 questionnaire. CONCLUSIONS: Although the lockdown period due to the COVID-19 pandemic has probably had a significant emotional impact on Spaniards with IBD, IBD patients in general had lower PSS-10 scores.

Risk Factors for Severe COVID-19 in Children.

BACKGROUND: There are limited pediatric data regarding severe COVID-19 disease. Our study aims to describe the epidemiology and identify risk factors for severe COVID-19 disease in children. METHODS: This is a retrospective cohort study among children with positive SARS-CoV-2 PCR from March to July 2020 at Children's Hospital Colorado. Risk factors for severe disease were analyzed as defined by hospital admission, respiratory support, or critical care. Univariable and multivariable analyses were conducted. RESULTS: Among 454 patients identified with SARS-CoV-2, 191 (42.1%) were females, median age 11 years. Fifty-five percent of all patients identified as Hispanic compared with 29% among all hospital visits in 2019 (P < 0.0001). In multivariable analyses, age 0-3 months or >20 years [adjusted odds ratio (aOR), 7.85; P < 0.0001 and aOR, 5.1; P = 0.03, respectively], preterm birth history (aOR, 3.7; P = 0.03), comorbidities [including immunocompromise (aOR, 3.5; P = 0.004), gastrointestinal condition (aOR, 2.7; P = 0.009), diabetes (aOR, 6.6; P = 0.04), asthma (aOR, 2.2; P = 0.04)], and specific symptoms at presentation were predictors for admission. Age 0-3 months or >20 years, asthma, gastrointestinal condition, and similar symptoms at presentation were also predictors for respiratory support. Elevated C-reactive protein was associated with the need for critical care with median of 17.7 mg/dL (IQR, 5.3-22.9) versus 1.95 mg/dL (IQR, 0.7-5.5) among patients requiring critical versus no critical care (OR, 1.2; P = 0.02). CONCLUSIONS: Extremes of age, comorbid conditions, and elevated CRP are predictors of severe disease in children. Findings from this study can inform pediatric providers and public health officials to tailor clinical management, pandemic planning, and resource allocation.

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs.

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

A Pediatric Infectious Diseases Perspective of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Novel Coronavirus Disease 2019 (COVID-19) in Children.

Understanding the role that children play in the clinical burden and propagation of severe acute respiratory syndrome coronavirus 2, responsible for coronavirus disease 2019 (COVID-19) infections, is emerging. While the severe manifestations and acute clinical burden of COVID-19 have largely spared children compared with adults, understanding the epidemiology, clinical presentation, diagnostics, management, and prevention opportunities and the social and behavioral impacts on child health is vital. Foremost is clarifying the contribution of asymptomatic and mild infections to transmission within the household and community and the clinical and epidemiologic significance of uncommon severe post-infectious complications. Here, we summarize the current knowledge, identify resources, and outline research opportunities. Pediatric infectious diseases clinicians have a unique opportunity to advocate for the inclusion of children in epidemiological, clinical, treatment, and prevention studies to optimize their care as well as to represent children in the development of guidance and policy during pandemic response.

Analysis of COVID-19 convalescent plasma for SARS-CoV-2 IgG using two commercial immunoassays.

Coronavirus Disease 2019 (COVID-19) convalescent plasma (CCP) was approved by the FDA for use in severe cases of COVID-19 under an emergency Investigational New Drug (IND) protocol. Eligibility criteria for CCP donors includes documentation of evidence of COVID-19 either by viral RNA detection at the time of illness or positive SARS-CoV-2 IgG after recovery if diagnostic testing for COVID-19 was not performed at the time of illness. In addition to analysis of CCP, analysis of SARS-CoV-2 IgG provides information for possible past exposure and may support diagnosis when SARS-CoV-2 PCR is negative and clinical suspicion for COVID-19 is high. Furthermore, assays with high sensitivity and specificity for SARS-CoV-2 IgG are critical for understanding community exposure rates to SARS-CoV-2. Currently, there are several assays that test for antibodies to SARS-CoV-2 using a variety of methods, including point-of-care lateral flow-based devices, high throughput immunoassay analyzers, and manual methods such as ELISA. These assays target a number of SARS-CoV-2 antigens, including the nucleocapsid protein (N), full length spike protein (S), S1 subunit, or receptor binding domain (RBD) of the S protein. Given the heterogeneity among methods for, and antigenic targets used in SARS-CoV-2 antibody assays, it is necessary for careful evaluation of these assays prior to implementation for clinical use. We compared two assays that had received the CE mark of regulatory approval and that used either the N antigen or S1-RBD antigen as the target for analysis of a large set of CCP samples. Our data indicates that sensitivity and specificity vary between these assays and that more than one antigenic target may be required to improve the sensitivity and specificity of IgG detection to SARS-CoV-2.