Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Are There Bad ICU Rooms? Temporal Relationship between Patient and ICU Room Microbiome, and Influence on Vancomycin-Resistant Enterococcus Colonization.

The gut microbiome of an individual can shape the local environmental surface microbiome. We sought to determine how the intensive care unit (ICU) patient gut microbiome shapes the ICU room surface microbiome, focusing on vancomycin-resistant Enterococcus (VRE), a common ICU pathogen. This was an ICU-based prospective cohort study. Rectal swabs were performed in adult ICU patients immediately at the time of ICU admission and environmental surface swabs were performed at five predetermined time points. All swabs underwent 16S rRNA gene sequencing and culture for VRE. 304 ICU patients and 24 ICU rooms were sampled (5 longitudinal samples per ICU room). Spatially adjacent ICU rooms were no more microbially similar than nonadjacent rooms. Microbial signatures within rooms diverged rapidly over time: in 14 days, ICU rooms were as similar to other ICU rooms as they were to their prior selves. This divergence over time was more pronounced in rooms with higher patient turnover. Examining VRE status by culture, patient VRE gut colonization had modest agreement with room surface VRE (kappa statistic 0.36). There were no ICU rooms that consistently cultured positive for VRE, including those that housed VRE positive patients. Individual ICU patients had a limited impact on ICU room surface microbiome, and rooms diverged similarly over time regardless of patients. Patient VRE gut colonization may have a modest influence on room surface VRE but there were no "bad rooms" that consistently cultured positive for VRE. These results may be useful in planning infection control measures. IMPORTANCE This study found that intensive care unit (ICU) room microbial signatures diverged from their baseline quickly: within 2 weeks, individual ICU rooms had lost distinguishing characteristics and were as similar to other ICU rooms as they were to their former selves. Patient turnover within rooms accelerated this drift. Patient gut colonization with vancomycin-resistant Enterococcus (VRE) was associated with ICU room surface contamination with VRE; again, within 2 weeks, this association was substantially diminished. These results provide dynamic information regarding how patients control the microbiota on local hospital room surfaces and may facilitate decision making for infection prevention and control measures targeting VRE or other organisms.

COVID-19 in Children.

Although COVID-19 has impacted many children, severe disease is rare and most recover with supportive care. Manifestations are diverse and often nonrespiratory. Adolescents/children with medical comorbidities are at risk for severe respiratory compromise. The most serious manifestation in previously healthy children is a delayed multisystem inflammatory syndrome with cardiac compromise in severe cases. Anti-SARS-CoV-2 monoclonal antibodies are available for adolescents at risk of progression and not hospitalized. Therapeutic options for severe respiratory disease with hypoxia include remdesivir and glucocorticoids. Therapies for multisystem inflammatory syndrome in children include intravenous immunoglobulin and glucocorticoids. Refractory cases may benefit from additional immunomodulators.

Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.

BACKGROUND: Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. CONCLUSIONS: Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.

Severe respiratory viral infections in children with history of asymptomatic or mild COVID-19.

IMPORTANCE: The spectrum of complications of COVID-19 in children, including the effect of COVID-19 on later viral infection, is not known. OBJECTIVE: To examine the features of children hospitalized for respiratory illness with history of prior COVID-19. DESIGN: Retrospective observational case series at a single pediatric quaternary medical center in New York City. Data were obtained from review of medical records. PARTICIPANTS: Children with prior mild or asymptomatic COVID-19 and no known risk factors for severe respiratory disease, who were hospitalized at our center for acute respiratory illness from October 2020 to May 2021, were reviewed. MAIN OUTCOMES AND MEASURES: Co-morbidities, history of prior COVID-19 symptoms, respiratory viral panel findings, acuity of illness, degree of respiratory decompensation based on support and interventions required, duration of hospitalization, and overall clinical course were assessed from the medical record. RESULTS: This study included 5 patients (median age, 4 years; age range: 0.8-9 years; 4 [80%] male). All had positive COVID-19 serology, 1 (20%) had mild symptoms, while the others had no symptoms of prior Sars-CoV-2 infection, 3 (60%) had asthma, and the remaining had no co-morbidities. All were admitted between April and May 2021. Two were re-admitted for respiratory symptoms in the subsequent 3 months. CONCLUSIONS AND RELEVANCE: This case series describes a possible association between severe lower respiratory tract infection and prior mild COVID-19 in children. Larger cohort studies describing the respiratory effects of prior COVID-19 in children are needed.

The Epidemiology of Respiratory Syncytial Virus in New York City during the Coronavirus Disease-2019 Pandemic Compared with Previous Years.

Fewer respiratory syncytial virus infections were observed in 2020-2021 with interseasonal resurgence. Children were more likely to have severe disease with less known risk factors in comparison with controls from 2018-2019. The overall codetection rates were similar, but with higher parainfluenza, rhinovirus/enterovirus, and lower influenza proportions compared with previous seasons.

Pediatric surgical site infection (SSI) following ambulatory surgery: Incidence, risk factors and patient outcomes.

BACKGROUND: Inpatient surgical site infections (SSIs) cause morbidity in children. The SSI rate among pediatric ambulatory surgery patients is less clear. To fill this gap, we conducted a multiple-institution, retrospective epidemiologic study to identify incidence, risk factors, and outcomes. METHODS: We identified patients aged <22 years with ambulatory visits between October 2010 and September 2015 via electronic queries at 3 medical centers. We performed sample chart reviews to confirm ambulatory surgery and adjudicate SSIs. Weighted Poisson incidence rates were calculated. Separately, we used case-control methodology using multivariate backward logistical regression to assess risk-factor association with SSI. RESULTS: In total, 65,056 patients were identified by queries, and we performed complete chart reviews for 13,795 patients; we identified 45 SSIs following ambulatory surgery. The weighted SSI incidence following pediatric ambulatory surgery was 2.00 SSI per 1,000 ambulatory surgeries (95% confidence interval [CI], 1.37-3.00). Integumentary surgeries had the highest weighted SSI incidence, 3.24 per 1,000 ambulatory surgeries (95% CI, 0.32-12). The following variables carried significantly increased odds of infection: clean contaminated or contaminated wound class compared to clean (odds ratio [OR], 9.8; 95% CI, 2.0-48), other insurance type compared to private (OR, 4.0; 95% CI, 1.6-9.8), and surgery on weekend day compared to weekday (OR, 30; 95% CI, 2.9-315). Of the 45 instances of SSI following pediatric ambulatory surgery, 40% of patients were admitted to the hospital and 36% required a new operative procedure or bedside incision and drainage. CONCLUSIONS: Our findings suggest that morbidity is associated with SSI following ambulatory surgery in children, and we also identified possible targets for intervention.

Predicting healthcare-associated infections, length of stay, and mortality with the nursing intensity of care index.

OBJECTIVES: The objectives of this study were (1) to develop and validate a simulation model to estimate daily probabilities of healthcare-associated infections (HAIs), length of stay (LOS), and mortality using time varying patient- and unit-level factors including staffing adequacy and (2) to examine whether HAI incidence varies with staffing adequacy. SETTING: The study was conducted at 2 tertiary- and quaternary-care hospitals, a pediatric acute care hospital, and a community hospital within a single New York City healthcare network. PATIENTS: All patients discharged from 2012 through 2016 (N = 562,435). METHODS: We developed a non-Markovian simulation to estimate daily conditional probabilities of bloodstream, urinary tract, surgical site, and Clostridioides difficile infection, pneumonia, length of stay, and mortality. Staffing adequacy was modeled based on total nurse staffing (care supply) and the Nursing Intensity of Care Index (care demand). We compared model performance with logistic regression, and we generated case studies to illustrate daily changes in infection risk. We also described infection incidence by unit-level staffing and patient care demand on the day of infection. RESULTS: Most model estimates fell within 95% confidence intervals of actual outcomes. The predictive power of the simulation model exceeded that of logistic regression (area under the curve [AUC], 0.852 and 0.816, respectively). HAI incidence was greatest when staffing was lowest and nursing care intensity was highest. CONCLUSIONS: This model has potential clinical utility for identifying modifiable conditions in real time, such as low staffing coupled with high care demand.

Central Venous Catheter Salvage in Ambulatory Central Line-Associated Bloodstream Infections.

BACKGROUND: Guidelines for treatment of central line-associated bloodstream infection (CLABSI) recommend removing central venous catheters (CVCs) in many cases. Clinicians must balance these recommendations with the difficulty of obtaining alternate access and subjecting patients to additional procedures. In this study, we evaluated CVC salvage in pediatric patients with ambulatory CLABSI and associated risk factors for treatment failure. METHODS: This study was a secondary analysis of 466 ambulatory CLABSIs in patients <22 years old who presented to 5 pediatric medical centers from 2010 to 2015. We defined attempted CVC salvage as a CVC left in place ≥3 days after a positive blood culture result. Salvage failure was removal of the CVC ≥3 days after CLABSI. Successful salvage was treatment of CLABSI without removal of the CVC. Bivariate and multivariable logistic regression analyses were used to test associations between risk factors and attempted and successful salvage. RESULTS: A total of 460 ambulatory CLABSIs were included in our analysis. CVC salvage was attempted in 379 (82.3%) cases. Underlying diagnosis, CVC type, number of lumens, and absence of candidemia were associated with attempted salvage. Salvage was successful in 287 (75.7%) attempted cases. Underlying diagnosis, CVC type, number of lumens, and absence of candidemia were associated with successful salvage. In patients with malignancy, neutropenia within 30 days before CLABSI was significantly associated with both attempted salvage and successful salvage. CONCLUSIONS: CVC salvage was often attempted and was frequently successful in ambulatory pediatric patients presenting with CLABSI.

Data Consult Service: Can we use observational data to address immediate clinical needs?

OBJECTIVE: A number of clinical decision support tools aim to use observational data to address immediate clinical needs, but few of them address challenges and biases inherent in such data. The goal of this article is to describe the experience of running a data consult service that generates clinical evidence in real time and characterize the challenges related to its use of observational data. MATERIALS AND METHODS: In 2019, we launched the Data Consult Service pilot with clinicians affiliated with Columbia University Irving Medical Center. We created and implemented a pipeline (question gathering, data exploration, iterative patient phenotyping, study execution, and assessing validity of results) for generating new evidence in real time. We collected user feedback and assessed issues related to producing reliable evidence. RESULTS: We collected 29 questions from 22 clinicians through clinical rounds, emails, and in-person communication. We used validated practices to ensure reliability of evidence and answered 24 of them. Questions differed depending on the collection method, with clinical rounds supporting proactive team involvement and gathering more patient characterization questions and questions related to a current patient. The main challenges we encountered included missing and incomplete data, underreported conditions, and nonspecific coding and accurate identification of drug regimens. CONCLUSIONS: While the Data Consult Service has the potential to generate evidence and facilitate decision making, only a portion of questions can be answered in real time. Recognizing challenges in patient phenotyping and designing studies along with using validated practices for observational research are mandatory to produce reliable evidence.

Household level SARS-CoV-2 sero-epidemiology in a high prevalence group of adults and children-implications for community infection control.

In 108 households (n = 474, 280 ≤ 18 years old), SARS-CoV-2 seroprevalence was significantly associated with age (range 37.5%-78.7%) and lowest in children ≤ 10 years old. Among 92 households with members ≤ 18, 14 (15.2%) had only a seropositive child or adolescent, while 16 (17.4%) had only seropositive adults. Households with both groups concurrently seropositive (n = 62) were larger in size (mean 8.11 ± 2.49) vs (mean 5.77 ± 2.31) (P < .001).

Longitudinal Outcomes for Multisystem Inflammatory Syndrome in Children.

BACKGROUND: In spring 2020, a novel hyperinflammatory process associated with severe acute respiratory syndrome coronavirus 2 multisystem inflammatory syndrome in children (MIS-C) was described. The long-term impact remains unknown. We report longitudinal outcomes from a New York interdisciplinary follow-up program. METHODS: All children <21 years of age, admitted to NewYork-Presbyterian with MIS-C in 2020, were included. Children were followed at 1 to 4 weeks, 1 to 4 months, and 4 to 9 months postdischarge. RESULTS: In total, 45 children were admitted with MIS-C. The median time to last follow-up was 5.8 months (interquartile range 1.3-6.7). Of those admitted, 76% required intensive care and 64% required vasopressors and/or inotropes. On admission, patients exhibited significant nonspecific inflammation, generalized lymphopenia, and thrombocytopenia. Soluble interleukin (IL) IL-2R, IL-6, IL-10, IL-17, IL-18, and C-X-C Motif Chemokine Ligand 9 were elevated. A total of 80% (n = 36) had at least mild and 44% (n = 20) had moderate-severe echocardiographic abnormalities including coronary abnormalities (9% had a z score of 2-2.5; 7% had a z score > 2.5). Whereas most inflammatory markers normalized by 1 to 4 weeks, 32% (n = 11 of 34) exhibited persistent lymphocytosis, with increased double-negative T cells in 96% of assessed patients (n = 23 of 24). By 1 to 4 weeks, only 18% (n = 7 of 39) had mild echocardiographic findings; all had normal coronaries. At 1 to 4 months, the proportion of double-negative T cells remained elevated in 92% (median 9%). At 4 to 9 months, only 1 child had persistent mild dysfunction. One had mild mitral and/or tricuspid regurgitation. CONCLUSIONS: Although the majority of children with MIS-C present critically ill, most inflammatory and cardiac manifestations in our cohort resolved rapidly.

Congenital Measles in a Premature 25-week Gestation Infant.

We describe a premature infant with congenital measles. Laboratory testing confirmed measles in the mother (polymerase chain reaction- and IgM-positive) and congenital measles in the infant (polymerase chain reaction-positive, culture-positive and IgM-positive). The infant never developed a rash, pneumonia, or neurologic complications. This case supports using compatible laboratory findings to diagnose congenital measles in infants without clinical manifestations of measles.

Spa Typing of Staphylococcus aureus in a Neonatal Intensive Care Unit During Routine Surveillance.

BACKGROUND: Staphylococcus aureus protein A (spa) typing can be used to expand characterization of the epidemiology of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in neonatal intensive care units (NICU). METHODS: From January 2017 to June 2018, twice-monthly surveillance for S. aureus was performed in an academically affiliated NICU. Decolonization of infants colonized with S. aureus included chlorhexidine gluconate bathing and/or mupirocin for those with mupirocin-susceptible strains. Spa typing and mupirocin-resistance testing were performed. Demographic and clinical characteristics were compared between infants colonized with MSSA vs MRSA and infants with and without the most common MSSA spa type, MSSA-t279. RESULTS: Overall, 14% and 2% of 1556 hospitalized infants had positive surveillance cultures for MSSA and MRSA, respectively. Thirty-six infants harbored unique MSSA spa types, 5 infants harbored unique MRSA spa types, and 30 MSSA and 6 MRSA spa types were identified in ≥2 infants. No outbreaks were identified during the study period. MSSA-t279 was isolated from 3% of infants and largely detected from infants hospitalized in one section of the NICU; 96% of t279 isolates were mupirocin resistant. Infection rates, length of hospitalization, and mortality were similar among infants initially colonized with t279 vs other MSSA spa types. CONCLUSIONS: The MSSA colonization burden was 5-fold larger than that of MRSA. Numerous unique spa types were identified. The most common spa type, MSSA-t279, was not associated with increased morbidity or mortality but was mupirocin resistant and associated with clustered NICU beds. This suggests potential transmission from the environment, shared staff, and/or workflow issues requiring further study. Other decolonization strategies for S. aureus in the NICU are needed.

Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

Pediatric Ambulatory Central Line-Associated Bloodstream Infections.

BACKGROUND: Inpatient pediatric central line-associated bloodstream infections (CLABSIs) cause morbidity and increased health care use. Minimal information exists for ambulatory CLABSIs despite ambulatory central line (CL) use in children. In this study, we identified ambulatory pediatric CLABSI incidence density, risk factors, and outcomes. METHODS: Retrospective cohort with nested case-control study at 5 sites from 2010 through 2015. Electronic queries were used to identify potential cases on the basis of administrative and laboratory data. Chart review was used to confirm ambulatory CL use and adjudicated CLABSIs. Bivariate followed by multivariable backward logistic regression was used to identify ambulatory CLABSI risk factors. RESULTS: Queries identified 4600 potentially at-risk children; 1658 (36%) had ambulatory CLs. In total, 247 (15%) patients experienced 466 ambulatory CLABSIs with an incidence density of 0.97 CLABSIs per 1000 CL days. Incidence density was highest among patients with tunneled externalized catheters versus peripherally inserted central catheters and totally implanted devices: 2.58 CLABSIs per 1000 CL days versus 1.46 vs 0.23, respectively (P < .001). In a multivariable model, clinic visit (odds ratio [OR] 2.8; 95% confidence interval [CI]: 1.4-5.5) and low albumin (OR 2.3; 95% CI: 1.2-4.3) were positively associated with CLABSI, and prophylactic antimicrobial agents for underlying conditions within the preceding 30 days (OR 0.22; 95% CI: 0.12-0.40) and operating room CL placement (OR 0.36; 95% CI: 0.16-0.79) were inversely associated with CLABSI. A total of 396 patients (85%) were hospitalized because of ambulatory CLABSI with an 8-day median length of stay (interquartile range 5-13). CONCLUSIONS: Ambulatory pediatric CLABSI incidence density is appreciable and associated with health care use. CL type, patients with low albumin, prophylactic antimicrobial agents, and placement setting may be targets for reduction efforts.

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.

BACKGROUND: In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (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 the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

Discriminating Multisystem Inflammatory Syndrome in Children Requiring Treatment from Common Febrile Conditions in Outpatient Settings.

OBJECTIVES: To examine whether patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated well-defined clinical features distinct from other febrile outpatients, given the difficulties of seeing acute care visits during the severe acute respiratory syndrome coronavirus 2 pandemic and the risks associated with both over- and underdiagnosis of MIS-C. STUDY DESIGN: This case-controlled study compared patients diagnosed with and treated for MIS-C at a large urban children's hospital with patients evaluated for fever at outpatient acute care visits during the peak period of MIS-C. Symptomatology and available objective data were extracted. Comparisons were performed using t tests with corrections for multiple comparisons, and multivariable logistic regression to obtain ORs. RESULTS: We identified 44 patients with MIS-C between April 16 and June 10, 2020. During the same period, 181 pediatric patients were evaluated for febrile illnesses in participating outpatient clinics. Patients with MIS-C reported greater median maximum reported temperature height (40°C vs 38.9, P < .0001), and increased frequency of abdominal pain (OR 12.5, 95% CI [1.65-33.24]), neck pain (536.5, [2.23-129,029]), conjunctivitis (31.3, [4.6-212.8]), oral mucosal irritation (11.8, [1.4-99.4]), extremity swelling or rash (99.9, [5-1960]), and generalized rash (7.42, [1.6-33.2]). Patients with MIS-C demonstrated lower absolute lymphocyte (P < .0001) and platelet counts (P < .05) and greater C-reactive protein concentrations (P < .001). CONCLUSIONS: Patients treated for MIS-C due to concern for potential cardiac injury show combinations of features distinct from other febrile patients seen in outpatient clinics during the same period.

Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing 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 noninvasive or invasive mechanical ventilation or extracorporeal 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 noninvasive 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.