Case report: Clinical course and treatment of SARS-CoV-2 in a pediatric CAR-T cell recipient with persistent hypogammaglobulinemia.

This report describes a pediatric patient who underwent chimeric antigen receptor (CAR) T-cell therapy for refractory B-cell acute lymphoblastic leukemia (B-ALL) four years prior, with resultant hypogammaglobulinemia for which he was receiving weekly subcutaneous immune globulin. He presented with persistent fever, dry cough, and a tingling sensation in his toes following a confirmed COVID-19 infection 3 weeks prior. His initial nasopharyngeal SARS-CoV-2 PCR was negative, leading to an extensive workup for other infections. He was ultimately diagnosed with persistent lower respiratory tract COVID-19 infection based on positive SARS-CoV-2 PCR from bronchoalveolar lavage (BAL) sampling. He was treated with a combination of remdesivir (antiviral) and casirivimab/imdevimab (combination monoclonal antibodies) with immediate improvement in fever, respiratory symptoms, and neurologic symptoms.

Multisystem inflammatory syndrome in children (MIS-C) and neonates (MIS-N) associated with COVID-19: optimizing definition and management.

During the SARS-CoV-2-associated infection (COVID-19), pandemic initial reports suggested relative sparing of children inversely related to their age. Children and neonates have a decreased incidence of SARS-CoV-2 infection, and if infected they manifested a less severe phenotype, in part due to enhanced innate immune response. However, a multisystem inflammatory syndrome in children (MIS-C) or paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 emerged involving coronary artery aneurysms, cardiac dysfunction, and multiorgan inflammatory manifestations. MIS-C has many similarities to Kawasaki disease and other inflammatory conditions and may fit within a spectrum of inflammatory conditions based on immunological results. More recently neonates born to mothers with SARS-CoV-2 infection during pregnancy demonstrated evidence of a multisystem inflammatory syndrome with raised inflammatory markers and multiorgan, especially cardiac dysfunction that has been described as multisystem inflammatory syndrome in neonates (MIS-N). However, there is a variation in definitions and management algorithms for MIS-C and MIS-N. Further understanding of baseline immunological responses to allow stratification of patient groups and accurate diagnosis will aid prognostication, and inform optimal immunomodulatory therapies. IMPACT: Multisystem inflammatory system in children and neonates (MIS-C and MIS-N) post COVID require an internationally recognized consensus definition and international datasets to improve management and plan future clinical trials. This review incorporates the latest review of pathophysiology, clinical information, and management of MIS-C and MIS-N. Further understanding of the pathophysiology of MIS-C and MIS-N will allow future targeted therapies to prevent and limit clinical sequelae.

Extending the Reach of Antimicrobial Stewardship to Pediatric Patients.

Guidance for developing and implementing antimicrobial stewardship programs for children is lacking. This review article describes unique considerations for planning antimicrobial management of children that may impact stewardship strategies. A variety of methods and training tools are described along with metrics specific to measuring antibiotic use and outcomes in children. Handshake stewardship is specifically explained and is considered a best practice. Information on stewardship in unique settings, including the neonatal intensive care unit and outpatient settings, are included.

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study.

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.

Increasing Use of Ambulatory Video Visits for Pediatric Patients by Using Quality Improvement Methods.

INTRODUCTION: Live video visits for ambulatory encounters offer potential benefits, including access to remote subspecialty services, care coordination between providers, and improved convenience for patients. We aimed to increase the utilization of video visits for pediatric patients at our medical center using an iterative quality improvement process. METHODS: A multispecialty improvement team identified opportunities to increase video visit utilization and prioritized interventions using benefit-effort analyses. Interventions focused on 6 key drivers. The outcome measure was the percentage of ambulatory encounters conducted by video. The process measure was the percentage of ambulatory pediatricians conducting video visits. The balancing measure was the percentage of no-shows among scheduled video visits. All measures were analyzed using statistical process control. RESULTS: Interventions were associated with increases in our outcome and process measures from 0.1% to 1.2% and 0.6% to 6.3%, respectively, during the first 8 months. Subsequently, the novel coronavirus (COVID-19) pandemic was associated with further increases in these measures to 41.8% and 73.5%, respectively, over 3 months. The balancing measure increased from 0% at baseline to 14.7% with no special cause variation during the intervention period. The most impactful interventions included clinician training outreach, providing equipment, and streamlining MyChart patient enrollment. CONCLUSIONS: This improvement project effectively increased pediatric ambulatory video visit utilization, although the most significant driver of utilization was the COVID-19 pandemic. Project interventions implemented before COVID-19 facilitated rapid video visit adoption during the pandemic. A similar improvement process may be beneficial for other medical centers aiming to improve video visit utilization.

Perinatal SARS-CoV-2 Infection and Neonatal COVID-19: A 2021 Update.

The coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept across the world like an indiscriminating wildfire. Pregnant women and neonates are particularly vulnerable to this infection compared with older children and healthy young adults, with unique challenges in their management. Unfamiliarity with the consequences of this novel virus and lack of high-quality data led to considerable heterogeneity in obstetrical and neonatal management early in the pandemic. The aim of the this review is to summarize the impact of SARS-CoV-2 infection on pregnancy and childbirth and to examine care and possible outcomes for neonates with Covid-19-positive mothers. A brief review of vaccines currently approved by the United States Food and Drug Administration for emergency use and their potential effects on pregnant and lactating women in included.

Evaluation of Seasonal Respiratory Virus Activity Before and After the Statewide COVID-19 Shelter-in-Place Order in Northern California.

Importance: Public health initiatives that include shelter-in-place orders are expensive and unpopular. Demonstrating the success of these initiatives is essential to justify their systemic or individual cost. Objective: To examine the association of a shelter-in-place order with lower rates of seasonal respiratory viral activity. Design, Setting, and Participants: This cohort study with interrupted time series analysis obtained monthly counts of respiratory virus testing results at UC Davis Health from August 1, 2014, to July 31, 2020. Patients of all ages underwent testing conducted by the laboratory at UC Davis Health, a referral center for a 65 000-square-mile area that includes 33 counties and more than 6 million Northern California residents. Exposures: A statewide shelter-in-place order was instituted on March 19, 2020, restricting residents to their homes except for traveling for essential activities. Large social gatherings were prohibited, schools were closed, and nonessential personnel worked remotely. Those who had to leave their homes were mandated to wear face masks, engage in frequent handwashing, and maintain physical distancing. Main Outcomes and Measures: Positivity rates of common respiratory viruses within the community served by UC Davis Health. Results: A total of 46 128 tests for viral respiratory pathogens over a 6-year period were included in the analysis. For the postexposure period (March 25-July 31), approximately 168 positive test results occurred for the studied organisms in the 2020 virus year, a positivity rate of 9.88 positive results per 100 tests that was much lower than the positivity rate of 29.90 positive results per 100 tests observed for this date range in the previous 5 virus years. In contrast, the positivity rates were similar for the preexposure time frame (August 1-March 24) in the 2020 virus year and for the same time periods in the 5 previous years (30.40 vs 33.68 positive results per 100 tests). In the regression analyses, statistically significant decreases in viral activity were observed in the postexposure period for influenza (93% decrease; incidence rate ratio [IRR], 0.07; 95% CI, 0.02-0.33) and for rhinovirus or enterovirus (81% decrease; IRR, 0.19; 95% CI, 0.09-0.39) infections. Lower rates of postexposure viral activity were seen for respiratory syncytial virus, parainfluenzavirus, coronaviruses, and adenoviruses; however, these associations were not statistically significant. Conclusions and Relevance: Using interrupted time series analysis of testing for viral respiratory pathogens, this study found that statistically significant lower rates of common community respiratory viruses appeared to be associated with a shelter-in-place order during the coronavirus disease 2019 pandemic.

Multisystem Inflammatory Syndrome in Children: Survey of Protocols for Early Hospital Evaluation and Management.

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.

Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). The clinical presentation of MIS-C includes fever, severe illness, and the involvement of two or more organ systems, in combination with laboratory evidence of inflammation and laboratory or epidemiologic evidence of SARS-CoV-2 infection. Some features of MIS-C resemble Kawasaki Disease, toxic shock syndrome, and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. Patients with MIS-C should ideally be managed in a pediatric intensive care environment since rapid clinical deterioration may occur. Specific immunomodulatory therapy depends on the clinical presentation. The relationship between the immune response to SARS-CoV-2 vaccines in development and MIS-C requires further study.

Are Perioperative Antibiotics Necessary During Direct Microlaryngoscopy?

OBJECTIVES/HYPOTHESIS: There are currently no established recommendations for the use of perioperative antibiotics (PAs) to prevent surgical site infections (SSIs) for direct microlaryngoscopy (DML). This study examined the incidence of SSI in patients undergoing DML with and without PAs. STUDY DESIGN: Retrospective, multi-institutional chart review. METHODS: A retrospective, multi-institutional chart review was performed at four tertiary referral academic medical centers. Patients undergoing DML from 2010 to 2017 were identified using Current Procedural Terminology codes. Medical records of patients undergoing DML with biopsy, microsurgery, laser ablation, or vocal fold injection who had adequate follow-up were reviewed. Procedures with significant cartilage destruction, concurrent open surgery, or esophageal surgery were excluded. Data recorded included age, gender, pacemaker history, American Society of Anesthesiologists class, wound class, indication for surgery, use of laser, complications, emergency room visits, hospitalizations, pain, fever, and postoperative steroid and antibiotic prescriptions. Presence or absence of SSIs was evaluated by a fellowship-trained laryngologist. RESULTS: There were 834 patients who met inclusion criteria. Of those, 698 did not receive PAs and 136 received PAs. The median age of patients was 54 years of age in the PA group and 57.5 years of age in the non-PA group, and all cases were recorded as wound class II. Overall, 58% of surgeries involved use of carbon dioxide or potassium-titanyl-phosphate laser. Only one SSI was reported on follow-up in a patient who did receive PAs. CONCLUSIONS: SSIs are exceedingly rare following DML. PA use is not indicated for routine DML. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2838-2843, 2018.

Loss of Innate Host Defense Following Unprotected Vaginal Sex.

BACKGROUND: Multiple host defense mechanisms protect the female genital tract from pathogens, but the impact of sexual intercourse on defense is unknown. METHODS: As part of a hypothesis-generating study, 17 women provided cervicovaginal lavage (CVL) specimens at baseline (all had abstained from sexual intercourse, masturbation, and vaginal product use for 72 hours prior to screening), 2-6 hours and 10-14 hours after vaginal intercourse with a male condom, and 2-6 hours and 10-14 hours after vaginal intercourse without a male condom (5 visits total, including the baseline visit). Vaginal pH, concentrations of immune molecules, and antimicrobial activity at postcoital visits were compared to baseline values. RESULTS: Vaginal pH and the transforming growth factor ß1 level increased, but human beta-defensin 2 (HBD-2), HBD-3, and interleukin 8 levels decreased after unprotected sex. Median Escherichia coli inhibitory activity in CVL specimens decreased significantly from baseline at the visit 2-6 hours after unprotected sex (63% [range, -34% to 99%] vs 5% [range, -51% to 100%]; P = .02) and remained low at the visit 10-14 hours after unprotected sex (6% [range, -19% to 92%]; P = .02). Pooled human seminal plasma enhanced E. coli growth in vitro in a dose-dependent manner and, when added to CVL samples with high anti-E. coli activity, reversed the inhibition. CONCLUSIONS: Unprotected vaginal sex results in a reduction in endogenous anti-E. coli activity, which may reflect, in part, enhancement of bacterial growth by seminal plasma. This finding may contribute to the risk of E. coli vaginal colonization following sexual intercourse.

Activity of Genital Tract Secretions and Synthetic Antimicrobial Peptides against Group B Streptococcus.

PROBLEM: Genital tract secretions inhibit Escherichia coli (E. coli) through antimicrobial peptides (AMP) secreted by the host and vaginal microbiota. However, there are limited data against group B Streptococcus (GBS). METHOD OF STUDY: Group B Streptococcus were incubated with cervico-vaginal lavage (CVL) samples from healthy non-pregnant women (n = 12) or synthetic AMP and monitored for bacterial growth using a turbidimetric approach. E. coli inhibitory activity was determined by a colony-forming unit assay. RESULTS: None of the CVL samples inhibited GBS. The human neutrophil peptide-1 and human defensin 5 inhibited GBS growth by ≥80% at concentrations ≥20 µg/mL and ≥50 µg/mL, respectively, while human beta-defensin 2 and LL-37 did not inhibit at highest concentration tested (100 µg/mL). In contrast, all AMP inhibited E. coli. CONCLUSIONS: Antimicrobial peptides may protect against E. coli colonization but have more limited activity against GBS. Future studies will focus on augmenting host defense with specific AMP to prevent genitourinary infection with these pathogenic organisms.