Inherited deficiency of the OAS-RNase L pathway in children with MIS-C

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Consistent with the absence of pneumonia in these patients, epithelial cells and fibroblasts defective for this pathway restricted SARS-CoV-2 normally. This contrasted with IFNAR1-deficient cells from patients prone to hypoxemic pneumonia without MIS-C. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV- 2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-but not RNase L- deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.Copyright © 2023 Elsevier Inc.

The Effect of COVID on Oral Reading Fluency During the 2020–2021 Academic Year

Education has faced unprecedented disruption during the COVID pandemic. Understanding how students have adapted as we have entered a different phase of the pandemic and some communities have returned to more typical schooling will inform a suite of policy interventions and subsequent research. We use data from an oral reading fluency (ORF) assessment—a rapid assessment taking only a few minutes that measures a fundamental reading skill—to examine COVID’s effects on children’s reading ability during the pandemic. We find that students in the first 200 days of the 2020–2021 school year tended to experience slower growth in ORF relative to prepandemic years. We also observe slower growth in districts with a high percentage of English language learners and/or students eligible for free and reduced-price lunch. These findings offer valuable insight into the effects of COVID on one of the most fundamental skills taught to children. © The Author(s) 2022.

Ring of disaster: Complication in percutaneous dilatational tracheostomy on ECMO

Introduction: Venous-venous extracorporeal membrane oxygenation (VV-ECMO) is becoming more utilized especially during the SARS-COV-2 pandemic. Although percutaneous dilatational tracheostomy (PDT) can be done and used safely to facilitate mechanical ventilation weaning, the procedure is associated with a higher complication rate when done in VV-ECMO patients. Case: 28-year-old male with past medical history significant for seizure disorder was transferred from outside hospital after getting treated for aspiration induced acute respiratory distress syndrome (ARDS). Decision was made to place the patient on VV-ECMO given refractory hypoxemia and hypercapnia with persistently high peak airway pressures. He was also placed on inhaled nitricoxide. Over the next 10 days, the patient was able to wean down to minimal ECMO settings. The decision was made to proceed with PDT to facilitate long term ventilation weaning. The tracheostomy was placed with minimal bleeding. Coagulopathy was optimized at that time. 24 hours after the procedure, the patient developed significant bleeding around the nasopharynx and the tracheostomy site. Patient's tidal volumes significantly decreased on pressure support ventilation leading to urgent inspection bronchoscopy. New clot burden was noted within the right bronchus intermedius. In addition, while entering the airway through the tracheostomy lumen, there was a valve-like ring of mucosal tissue that was semi-obstructing the lumen with each ventilation. The tissue was unable to be removed at the time. Unfortunately, the patient had a respiratory acidosis associated PEA arrest. He was able to regain pulse after 2 rounds of CPR and adjustment of sweep on ECMO. Second look bronchoscopy was done. Previously noted mucosal tissue appeared to be dislodged into the right main stem along with fibrous clot burden. Patient regained the previous tidal volume on the ventilator after the mucosal tissue and fibrous clot burden was removed. The bleeding was eventually controlled with supportive care. Eventually, the patient was able to be successfully decannulated from the ECMO and transferred back to the prior institution for further ventilation weaning. Discussion: ECMO patients often have increased hemorrhagic risk and post procedural complications given the circuit-blood interaction that affects coagulation and platelet function. Our case demonstrated rare potential severe complication peri-procedure. Insertion of a tracheostomy in an edematous airway can sheer mucosa and create the flap that can potentially lead to cardiac arrest. Early bronchoscopy surveillance may be warranted after PDT on patients with VV-ECMO to avoid unexpected complication. VV-ECMO setting should be adjusted when ventilation issues occur.