Background: The Bronx has the highest prevalence of asthma in the United States (US), and was also an early COVID-19 epicenter, making it a unique study location. Worldwide reports describe significant declines in pediatric emergency department (PED) visits during COVID-19. The ongoing impact of COVID-19 on all PED presentations, including asthma, at an early epicenter has not been studied beyond the pandemic peak and into the early phases of state re-opening. Objectives: To compare PED health-seeking behaviors and clinical characteristics during the 2020 pandemic and subsequent initial New York State (NYS) phased re-opening to the same period in 2019. Methods: Retrospective chart review of children <21 years utilizing the PED at a high-volume quaternary children's hospital in The Bronx, NY from March 15th 2020 -July 6th 2020 (pandemic cohort) and the same interval in 2019 (comparison cohort). Visits were assigned to pre-determined diagnostic categories. Demographic and clinical data were compared. Results: 19,981 visits were included. Visits declined by 66% during 2020. Proportions of asthma visits (2% vs. 7%, p < 0.0001) and minor medical problems (61% vs. 67%, p < 0.0001) had significant declines in the pandemic cohort, while major medical problems (13% vs. 8%, p < 0.0001), appendicitis (1% vs. 0.4%, p < 0.0001) and other surgical complaints (1% vs. 0.5%, p < 0.0001) had proportional increases in the pandemic cohort. No significant proportional changes were noted among psychosocial and trauma groups between the two cohorts. Conclusion:The pandemic cohort experienced a substantial decrease in PED volume, but an increase in acuity and admission rates, which was sustained through the NYS phase-II re-opening. Despite being located in an asthma hub, the incidence of asthma-related PED visits declined appreciably in the pandemic cohort. Future studies examining the effects of indoor allergens in isolation on pediatric asthma are warranted.

There is a paucity of research on the quality and quantity of clinical teaching in the emergency department (ED) setting. While many factors impact residents' perceptions of attending physicians' educational skill, the authors hypothesized that the amount of time residents spend with attending in direct teaching is a determinant of residents' perception of their shift's educational value. Researchers shadowed emergency medicine (EM) attendings during ED shifts, and recorded teaching time with each resident. Residents were surveyed on their assessment of the educational value (EV) of the shift and potential confounders, as well as the attending physician's teaching quality using the ER Scale. The study was performed in the EDs of two urban teaching hospitals affiliated with an EM residency program. Subjects were EM residents and rotators from other specialties. The main outcome measure was the regression of impact of teaching time on EV. Researchers observed 20 attendings supervising 47 residents (mean 2.35 residents per attending, range 2-3). The correlation between teaching time in minutes (mean 60.8, st.dev 25.6, range 7.6-128.1) and EV (mean 3.45 out of 5, st. dev 0.75, range 2-5) was significant (r = 0.302, r = 0.091, p< 0.05). No confounders had a significant effect. The study shows a moderate correlation between the total time attendings spend directly teaching residents and the residents' perception of educational value over a single ED shift. The authors suggest that mechanisms to increase the time attending physicians spend teaching during clinical shifts may result in improved resident education.

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To date, there are no approved oral antiviral therapies that can be administered early in the course of COVID‐19 to suppress progression of the disease or for prophylaxis. EDP‐235 is a potent and selective inhibitor of SARS‐CoV‐2 3C‐like protease (3CLpro). EDP‐235 inhibits SARS‐CoV‐2 3CLpro protease activity with an IC50 of 5.8 ± 3.7 nM and retains its activity against variant 3CLpro proteins from multiple SARS‐CoV‐2 lineages (IC50range of 2.8­–5.8 nM). 3CLpro protease activity progress curves showed significant curvature in a time‐ and EDP‐235‐concentration‐dependent manner indicative of slow‐onset inhibition. Slow reversal of inhibition of SARS‐CoV‐2 3CLpro enzyme activity was observed in a jump dilution experiment. Michaelis‐Menten kinetic studies with a FRET peptide substrate in the presence of EDP‐235 indicated that EDP‐235 is a substrate‐competitive inhibitor of SARS‐CoV‐2 3CLpro with an overall dissociation constant Kiof 3.0 ± 1.6 nM. SARS‐CoV‐2 3CLpro was crystallized bound to a close analog of EDP‐235 and structure elucidation revealed that the ligand bound at the active site and interacted with side chains of conserved residues Cys‐145, His‐163, and Glu‐166. EDP‐235 also potently inhibits 3CLpro enzymes from other α‐coronaviruses (IC50range of 2–4 nM) and β‐coronaviruses (SARS‐CoV IC50 of 5.4 nM, MERS‐CoV IC50 of 70 nM) which cause disease in humans to date. EDP‐235 resistance mutations in HCoV‐229E map to the active site of 3CLpro close to the predicted binding site and offer additional support to the mechanism of inhibition. EDP‐235 also showed a favorable selectivity profile (>300 selectivity index) when tested against a panel of 30 mammalian proteases. In summary, EDP‐235 acts as a slow‐onset, slow‐reversible, substrate‐competitive inhibitor of SARS‐CoV‐2 3CLpro. The outstanding preclinical profile of EDP‐235 supports its further evaluation as an oral therapeutic for the management of COVID‐19.

Coarctation of the aorta (CoA) is a congenital cardiac malformation that is well understood. Despite being well characterized, CoA is a commonly missed congenital heart disease (CHD) during the newborn period. We report a full-term nine-day-old male who presented to the pediatric emergency department (ED) with isolated tachypnea. After an initial sepsis workup, subsequent investigations revealed critical CoA. Because the primary workup focused on sepsis, there was a significant delay in prostaglandin E1 (PGE1) initiation. This case illustrates the importance of early CoA recognition and timely initiation of PGE1 in newborns who present with suspected sepsis along with tachypnea.