Background Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. Methods A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. Results Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. Conclusions Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

Background/Objectives: There has been a recent marked increase in pediatric and adult patients presenting with purpuric acral lesions concerning for ischemia, thrombosis and necrosis in COVID-19 prevalent regions worldwide. The clinical and histopathological features and relationship to COVID-19 have not been well described. The objective of this case series is to describe the clinical features and determine the histopathologic findings and clinical implications of the clusters of acral perniosis cases identified in pediatric patients.Methods: We describe 6 otherwise healthy adolescents -3 siblings per family from 2 unrelated families -presented within a 48-hour period in April, 2020, with acral perniosis-like lesions in the context of over 30 similar patients who were evaluated within the same week. Accepted ArticleThis article is protected by copyright. All rights reserved Results: Affected patients had mild symptoms of viral upper respiratory infection (URI) or contact with symptomatic persons 1-2 weeks preceding the rash. They all presented with red to violaceous macules and dusky, purpuric plaques scattered on the mid and distal aspects of the toes. Skin biopsies performed on each of the 6 patients demonstrated near identical histopathologic findings to those of idiopathic perniosis, with a lymphocytic inflammatory infiltrate without evidence of thromboembolism or immune complex vasculitis. While SARS-CoV-2 polymerase chain reaction was negative, testing was performed 1-2 weeks after URI symptoms or sick contact exposure.Conclusion: We offer a clinical approach to evaluation of patients with this presentation and discuss the possibility that these skin findings represent a convalescent-phase cutaneous reaction to SARS-CoV-2 infection.

Background Although Coronavirus Disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data evaluating agents with potential antiviral activity continue to expand, such that updated guidance is needed regarding use of these agents in children. Methods A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. Results Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for non-invasive or invasive mechanical ventilation or extra-corporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or non-invasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. Conclusions Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

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Defining the metabolic capabilities and regulatory mechanisms controlling gene expression is a valuable step in understanding the pathogenic properties of infectious agents such as Borrelia burgdorferi. The present studies demonstrated that B. burgdorferi encodes functional Pfs and LuxS enzymes for the breakdown of toxic products of methylation reactions. Consistent with those observations, B. burgdorferi was shown to synthesize the end product 4,5-dihydroxy-2,3-pentanedione (DPD) during laboratory cultivation. DPD undergoes spontaneous rearrangements to produce a class of pheromones collectively named autoinducer 2 (AI-2). Addition of in vitro-synthesized DPD to cultured B. burgdorferi resulted in differential expression of a distinct subset of proteins, including the outer surface lipoprotein VlsE. Although many bacteria can utilize the other LuxS product, homocysteine, for regeneration of methionine, B. burgdorferi was found to lack such ability. It is hypothesized that B. burgdorferi produces LuxS for the express purpose of synthesizing DPD and utilizes a form of that molecule as an AI-2 pheromone to control gene expression.

Background Pediatric oncology patients are at increased risk for invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count (ANC) ≥500/μl) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical utility. Methods A six-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia, the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding two less clinically reliable variables was also created using the initial EsVan model derivative cohort, and validated using all five external validation cohorts. One dataset was only used in sensitivity analyses due to missing some variables. Results From the five primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C-statistic for predicting bacteremia was 0.695 with a 0.50 calibration slope for the original model and 1.0 calibration slope when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (Gram negative or Staphylococcus aureus infection) versus BSI alone with a C-statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across datasets with a C-statistic 0.733 for predicting BSI and 0.841 for high-risk BSI. Conclusions This external validation shows that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and could assist in decision making in clinical practice once validated and implemented prospectively.

Background In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for two novel virus-neutralizing monoclonal antibody therapies, bamlanivimab, and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate COVID-19 in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. Results The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. Conclusions Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence, and ensure implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

KI virus was detected in respiratory secretions of 8/367 (2.2%) symptomatic and 0/96 asymptomatic children (p = 0.215). WU virus was detected in 26/367 (7.1%) of symptomatic children and 6/96 (6.3%) asymptomatic children (p = 1.00). These human polyomaviruses may not independently cause respiratory tract disease in young children. I n 2007, 2 new human polyomaviruses, KI virus (KIV)and WU virus (WUV), were identifi ed by molecular screening of respiratory secretions from children <2 years of age with symptomatic respiratory tract disease (1,2). Both viruses have since been detected in asymptomatic children and in those concurrently infected with other respiratory viruses, suggesting that KIV and WUV may not cause respiratory tract disease (3-5). To further understand the epidemiology of these viruses in young children and to clarify their association with symptomatic respiratory tract infections in this age group, we screened respiratory specimens from both asymptomatic and symptomatic children for the presence of KIV and WUV. The StudyRespiratory specimens from 2 groups of children (all <2 years of age) were collected in 2004 and screened for KIV and WUV. The fi rst group comprised symptomatic children whose respiratory specimens were submitted to the Clinical Virology Laboratory, Yale-New Haven Hospital, New Haven, Connecticut. These respiratory specimens tested negative for respiratory syncytial virus (RSV), parainfl uenza viruses (types 1-3), infl uenza viruses A and B, and adenovirus by direct fl uorescence antibody assay. The second group comprised asymptomatic children at the hospital-affi liated pediatric clinic for well-child care. Nucleic acids were extracted from each specimen by using QIAamp nucleic acid purifi cation kits (QIAGEN, Valencia, CA, USA). Samples were screened by nested PCR for both KIV and WUV (for WUV, the fi rst primers were those used by Gaynor et. al., and the nested primers were 5′-GCGCATCAAGAGGCACAGCTACTATTTC-3′ and 5′-GCGCCTAGCCTGTGAACTCCATC-3′). The G/C clamp for each primer is underlined. (1,2). Positive and negative controls were included in each set of PCRs. All PCR products were sequenced. Any child who had multiple specimens with positive results was included once in the total number of children whose specimens tested positive for a given virus.Specimens from symptomatic children who tested positive for KIV or WUV were also screened for human bocavirus (HBoV); human metapneumovirus (hMPV); human coronaviruses (HCoV) 229E, NL63, and HKU1; and human picornaviruses (including rhinoviruses [HRV]) by using previously described methods (6-12). To screen for human parainfl uenzavirus type 4 and HCoV OC43, RNA extraction and reverse transcription were performed as previously described (7). The primers used to amplify hPIV4 were 5′-GCGAGAGGATCCAGCTGGTGGC-3′ and 5′-GCGCCCTAATCTTTCCTGTTGATGG-3′. The primers for HCoV-OC43 were 5′-GCATAAGCCCC GCCAGAAGAGGAG-3′ and 5′-GCGCTGACGCTGTG GTTTTGGACT-3′.We tested 423 direct fl uorescent antibody-negative respiratory specimens, from 367 children,...