Placental Thrombosis Resulting in Hypoxic Ischemic Encephalopathy in an Infant of a Mother with Covid-19

Case Report: Since the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic, there has been much work to understand the negative effects of SARS-CoV-2 on tissues expressing the Angiotensin Converting Enzyme-2 (ACE2) receptor, including the placenta. However, there is limited information regarding placental pathology findings in mothers with COVID-19 and the effects of SARS-CoV-2 on the placenta. The available research reports effects on the fetus ranging from minimal to intrauterine fetal demise. Case Description: A 4680g baby boy was born at 38+1 weeks of gestation to 36y old G4P1021 female via repeat cesarian section. The pregnancy was complicated by advanced maternal age, chronic hypertension with superimposed pre-eclampsia with severe features, BMI of 80, and SARS-CoV-2 infection. The mother had mild COVID-19 symptoms and did not require hospitalization or oxygen support. Prenatal ultrasounds were limited due to body habitus. At the time of delivery, there was clear amniotic fluid. Upon delivery the infant was cyanotic and limp and was brought to the warmer immediately. Non-invasive positive pressure ventilation was initiated at 5 minutes of life with improvement in infant color and oxygen saturation. He was then admitted to the Neonatal Intensive Care Unit (NICU). APGARs were 2, 3, 5, and 7 at 1, 5, 10, and 15 minutes respectively. Cord gases showed severe metabolic acidosis. The patient was diagnosed with hypoxic-ischemic encephalopathy (HIE) and therapeutic hypothermia was initiated. Both the NICU and obstetric teams were unable to identify a clear perinatal cause of HIE in this patient. Later, the placenta pathology report revealed a large placenta for estimated gestational age corresponding to the 75th percentile, villous parenchyma with focal chorangiosis and thrombi, with unremarkable fetal membrane and three vessel umbilical cord. The cause of HIE was then thought to be due to the placental thrombi likely caused by SARS-CoV-2 infection. Discussion(s): Fetal vascular malperfusion and fetal vascular thrombus have been noted as a common finding in the placentas of pregnant women who test positive for SARS-CoV-2. There are various causes of HIE, from maternal, placental and fetal factors. This patient had no clinically evident hypoxic event, but information was limited due to the lack of monitoring of the fetus in utero. Given the mother's SARS-CoV-2 infection and the placental pathology findings, it is likely that the cause of this patient's HIE was related to the effects on the placenta from SARS-CoV-2. Conclusion(s): As more information comes to light about the effects of SARS-CoV-2 on the placenta, it is important to consider a maternal SARS-CoV-2 infection during pregnancy as a cause of HIE in a newborn.

Persistence of Symptoms One Year after Multisystem Inflammatory Syndrome in Children

Background: Long term evolution of Multisystem Inflammatory Syndrome in children (MIS-C) is poorly understood. In this report, we described the frequency of persistent symptoms and sequels after one-year monitoring in a cohort of MIS-C patients. Method(s): This is a prospective observational study in under-18-aged patients diagnosed with MIS-C between October 2020 and April 2021 in a tertiary hospital. Data from initial episode was obtained from the Spanish national database and the medical history. A standardized phone questionnaire was done one year after the acute episode. As patients pared by age and sex were included with i) history of acute COVID-19, from the same national database, and ii) with peritonitis diagnosis in the electronic medical record. Data was collected using REDCap and analysed with R. Ethics committee approval was obtained. Result(s): A total of 48 patients were included in the study, 16 in each group. Average age at hospitalization was 11,2 years old [IQR: 6,6-14,4] and 52% (23/48) were male. MIS-C patients presented high frequently 94% (15/16) cardiological complications during hospitalization, in contrast with 19% (3/16) of acute COVID-19 patients and 25% (4/16) of peritonitis group (p< 0.01). All of them resolved after a year except the ones associated to hypoxic ischemic encephalopathy in a patient with MIS-C that need ECMO assistance. Summary characteristics during acute episode are shown in Table 1. After one-year follow-up, 88% MIS-C patients suffered one or more symptoms, more frequently: headache (44%), fatigue (38%), insomnia (38%) and concentration problems (38%). A total of 56% of COVID-19 patients presented persisted symptoms, mainly fatigue and concentration problems (19%), and 31% in peritonitis group (19% loss of appetite and abdominal pain), (p< 0.001). MIS-C patients visited more frequently the medical professionals due to emotional change, behaviour or interpersonal relationships after the disease [4/16 (25%) in MIS-C vs. 0/16 (0%) in both control groups, p= 0.028]. Conclusion(s): Majority of MIS-C patients have persistent symptoms one year after acute episode, even with the resolution of cardiological complications. Frequency of long term symptoms in MIS-C patients is significantly higher than in COVID-19 hospitalized and than in a control group of surgical peritonitis patients. Summary characteristics during acute episode.

Special considerations in the premature and ex-premature infant

Advances in neonatal medicine have progressively increased the survival of premature infants. Increased survival has however come at the cost of increased number of infants with prematurity-related complications. This is represented by high rates of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, periventricular leukomalacia (PVL), intraventricular haemorrhage (IVH), cerebral palsy, hypoxic ischaemic encephalopathy (HIE) and visual and hearing problems in survivors. In addition to prolonged hospital stay after birth, readmission to hospital in the first year of life is common if chronic lung disease exists. Around 3% of newborns have a congenital physical anomaly with 60% of congenital anomalies affecting the brain or heart and around 1% having multiple anomalies. Individual congenital conditions requiring surgical intervention in the neonatal period are rare. Neonates have a higher perioperative mortality risk largely due to the degree of prior illness, the complexity of their surgeries, and infant physiology. The maintenance of oxygenation and perfusion in the perioperative phase is critical as both affect cerebral perfusion and neurocognitive outcome but the triggers for intervention and the thresholds of physiological parameters during neonatal anaesthesia are not well described. After even minor surgical procedures, ex-premature infants are at higher risk for postoperative complications than infants born at term.Copyright © 2022

The post-pandemic re-organization of birth centres and its impact on perinatal asphyxia in the province of Reggio Emilia

Objective. The pandemic forced the re-organization of birth hospitals in the province of Reggio Emilia. In 2018 there were four difference birth centres, in 2021 only two out of four were still working. The OBJECTIVE of the study was to evaluate if the centralization of birth centres had worsened the stillbirth rate and perinatal asphyxia (PA) outcome during the SARSCoV- 2 pandemic period (years 2020-21) compared to the pre-pandemic period (years 2018-19). Materials and Methods. Retrospective review of birth rate, recovery for PA rate and stillbirth rate in the province of Reggio Emilia. Results. Statistical data showed a decrease of overall births from 2018 to 2021 (7516 newborns in 2018-19 to 6363 in 2020- 21), in accordance with the national trend. The percentage of newborns in the NICU in Reggio Emilia increased from the pre-pandemic period (59.66%) to the pandemic period (83.66%). Regarding the stillbirth rate, we observed a decrease from the pre-pandemic period (3.20%) to the pandemic period (2.36%). As far as concerned the PA rate, the percentage showed a reduction from the pre-pandemic (0.44%) to the pandemic period (0.36%). We also observed a decrease of the hypoxic-ischemic encephalopathy (HIE) rate from 0.16% to 0.12%. Finally, three different outcomes were evaluated in patients admitted for perinatal asphyxia: mortality, brain imaging lesions and seizures. During the pandemic we observed a significant decrease in all of these (Table 1). Conclusions. Centralization of birth centres did not worsen perinatal diseases as far as concerns stillbirth, PA and HIE rate. On the contrary, we observed an enhancing of patients' outcomes.

Abstracts of 16th Congress of Pediatric Emergencies and Common Diseases

The proceedings contain 52 papers. The topics discussed include: cardiac presentation of multisystem inflammatory syndrome in children (MIS-C);monitoring of the patient with shock;factors influencing the prognosis of HIE of the newborn;problems and solutions in the field of neonatal research;new biomarkers in the diagnosis of hypoxic ischemic encephalopathy;is umbilical cord nucleated red blood cell count related to a premature baby prognosis?;COVID-19 and children with renal disease;accuracy of ultrasound in the diagnosis of skull fractures in the pediatric emergency department;comparing emergency residents with pediatric residents for their skills of ECG interpretation;adolescent's spiritual health in COVID-19 pandemic: a qualitative study;fluid challenge in children patients with COVID-19 disease;and drug-induced pulmonary toxicity: lots of drugs and chemical agents can cause acute and chronic lung injury.

Ischemic and Hemorrhagic Cerebrovascular Events Related to COVID-19 Coagulopathy and Hypoxemia.

Since the very beginning of the COVID-19 pandemic, numerous researchers have made an effort to determine the molecular composition of the SARS-CoV-2 virus, and the exact pathomechanism through which the virus exerts such a devastating effect on the host/infected organism. Recent scientific evidence highlights the affinity of the virus towards ACE2 receptors, which are widespread in multiple human systems, including the central nervous system (CNS) and cerebral vessels. Such an affinity may explain endothelial dysfunction and damage that is observed in COVID-positive patients in histopathological studies, with subsequent dysregulation of the cerebral circulation leading to transient or acute cerebrovascular accidents. In this paper, we aimed to evaluate the effects of COVID-related hypoxemia and direct viral invasion on the cerebral circulation, with special respect to the postulated pathomechanism, vulnerable groups of patients, clinical course and outcomes, as well as diagnostic imaging findings.

Mesenchymal Stem/Stromal Cells: ENDOGENOUS NON-TUMORIGENIC PLURIPOTENT MUSE CELLS;BASIC RESEARCH AND CLINICAL TRIALS

Background & Aim: Multilineage-differentiating stress enduring (Muse) cells, collectable as pluripotent surface marker SSEA-3-positive, are naturally existing non-tumorigenic pluripotent stem cells that distribute in the bone marrow, peripheral blood, connective tissue of every organ, and exhibit triploblastic differentiation and self-renewability at a single cell level. They are also contained in cultured MSCs and fibroblasts as several percent, and are expandable to a clinical scale. Circulating Muse cells, both endogenous and intravenously injected exogenous cells, selectively home to damaged tissue by sensing sphingosine-1-phosphate (S1P), one of the general alert signals produced by the damaged tissue, and then spontaneously differentiate into multiple tissue-constituent cells to replace damaged/ apoptotic cells. In this manner, they repair tissues. In addition, they have a specific immunomodulatory system, represented by HLA-G expression, allowing allogenic-Muse cells to directly administrate to patients without HLA-matching or long-term immunosuppressant (Figure Presented) treatment, and to remain in the host tissue as differentiated functional cells for more than half a year, as shown by animal models. Methods, Results & Conclusion: For these characteristics, intravenous drip is the main route of treatment and do not require surgery for their administration, nor do they require gene introduction or cytokine treatment to be rendered pluripotency and/or differentiation. Currently, clinical trials using intravenously administered donor- Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, amyotrophic lateral sclerosis and COVID19-ARDS, all by intravenous drip of donor-derived Muse cell formula, CL2020, without HLA-matching or immunosuppressant treatment. The result of randomized, double-blind, placebo-controlled clinical trial in stroke patients confirmed safety and efficacy of Muse cell-based product for up to 52 weeks (1 year). Muse cells may safely provide beneficial effects compatible with the ‘body’s natural repair systems’ by a simple cost- effective strategy;collection, expansion and intravenous drip.

Coronavirus 2019:clinical and neuropathological aspects

Objective: To describe the clinicopathological correlations of 141 confirmed postmortem cases of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome-coronavirus -2 (SARS-CoV-2). Background: Analysis of 50 cases of COVID-19 with available neuropathology revealed three CNS findings. First, hypoxia-ischemia does not account for all relevant neuropathological features. Second, elevated levels of circulating cytokines suggest activation of post-infectious immunity indicative of a cytokine storm, with increased hypercoagulability leading to a risk for thrombotic and hemorrhagic parenchymal tissue infarction. Third, a minority of cases have acute demyelinating encephalomyelitis-(ADEM) like features or indolent brainstem encephalitis. Such cases may present with early altered sensorium and brainstem signs. Fourth, SARS-CoV-2 staining could not be confirmed due to paucity of available tissue specimens. Design/Methods: Ninety-four additional cases with available postmortem CNS neuropathology showed four additional findings. Results: First, positive SARS-CoV-2 genome by PCR testing is present in brain tissues especially in olfactory bulb neurons and glial cells lending support to a route of entry into the CNS and the importance of early anosmia. Second, SARS-CoV-2-positive neurons appear to be TUNEL positive and caspase-positive, displaying reversible pT231 Tau localization in some cell soma that may be highly neurotoxic and a driver of tauopathy. Third, expression of ACE2 in oligodendrocytes is associated with viral entry, while TMPRSS2 and TMPRSS4 staining is implicated in pruning of viral-decorating spikes. Fourth, meningeal and interstitial brainstem inflammation by cytotoxic T-cells coincides with the localization of SARS-CoV-2 viral proteins in cranial nerves and interstitial areas of lower brainstem encephalitis. The detection of brain microglial activation and sparse perivascular and leptomeningeal T-cell infiltrates correlates with critical illness encephalopathy. Conclusions: Genetic diversity, recombination, and viral mutation carries the foreseeable risk of continued fatality due to the direct and indirect effects of SARS-CoV-2 that include inflammatory vasculopathy, encephalitis, silent infarctions, and critical illness encephalopathy.

Therapeutic Hypothermia in Neonatal Encephalopathy: Creating a Post-Pandemic Playbook

Objective: The aim of this initiative was to look into the impact of the COVID-19 pandemic on inpatient EEG, particularly in neonatal encephalopathy. Background: Hypoxic Ischemic Encephalopathy (HIE) is the most common cause of neonatal seizures (Glass et al., 2009). Higher seizure burden is associated with more severe brain injury and worse neurodevelopmental outcomes (Srinivasakumar et al., 2015). During the COVID-19 pandemic, a monumental shift in care delivery diverted resources to focus on patients with COVID-19. While this led to known delays in outpatient and elective EEG studies, many guidelines maintained the necessity for inpatient EEG, particularly for Neonatal Hypoxic Ischemic Encephalopathy. Design/Methods: At a tertiary care academic center between March 2020-September 2021, 30 neonates diagnosed with neonatal encephalopathy underwent therapeutic hypothermia (TH). Adherence to institutional TH protocol was defined as continuous EEG (cEEG) within 6 hours of TH initiation with repeat at 12-24 hours of normothermia. Time to cEEG placement was evaluated. Results: In this cohort, time to cEEG appeared to positively correlate with overall COVID-19 hospitalization rates in the region. During Summer 2020 (June-September), time to cEEG consistently was below 6 hours, with an average of 3.4 hours. When COVID-19 cases increased in Fall 2020 to Spring 2021 (November-March), time to cEEG drastically increased to an average of 14.2 hours. Conclusions: This data shows an increase in the average time to initiation of cEEG in TH was significantly different between these two time periods of the pandemic (p=0.0044). There are likely a number of factors which contribute to these findings, including EEG availability, staff and tech availability, as well as overall hospital resources. We are limited by a small sample size. However, this data illustrates the need for new strategies to maintain optimal patient care during times of limited resources.

Early detection of cerebral palsy among a high-risk cohort in low resource settings

Objective: Delayed diagnosis of cerebral palsy (CP) limits access to early interventions when the infant brain has the most neuroplastic potential, particularly in low-and middle-income countries (LMICs). The 2017 clinical guideline on the early diagnosis of CP outlines best practice tools to support diagnosis. We aimed to assess the feasibility of implementing these tools for early detection of CP in Bangladesh. Design: Prospective cohort study. Method: Neonates admitted to a regional tertiary hospital neonatal intensive care unit (NICU) in Bangladesh with major risk factors for CP (preterm birth, hypoxic ischemic encephalopathy/ neonatal encephalopathy [HIE/NE], neonatal sepsis and/or severe jaundice/kernicterus) were enrolled. A physician identified eligible neonates via physical assessment, medical record review and parent interview using a risk factor questionnaire developed for this study. General Movements Assessment (GMA) were completed at the time of recruitment (writhing period) and 13 weeks corrected age (fidgety age);neuroimaging data collected from the NICU;and Hammersmith Infant Neurological Examination (HINE) conducted at 12 months corrected age. Due to the impact of COVID-19, a proportion of the cohort were not able to have GMA fidgety videos completed and the first HINE assessment was delayed to 12 months. GMA data is not currently reported in this . Results: A total of 227 high risk neonates were recruited between November 2019 to March 2020. All neonates had evidence for prematurity and infection/sepsis on physical examination, 83.7% (n = 190) had HIE/NE and 14.5% (n = 33) had severe jaundice/kernicterus. Only 1.8% (n = 4) had cranial ultrasound and none had magnetic resonance imaging. Of the surviving (76.7%, n = 174) infants, 77.0% (n = 134) were assessed at 12 months. Among them, writhing videos and fidgety videos were previously collected for 100% (n = 134) and 29.9% (n = 40) respectively. At 12 months, 32.1% (n = 43) infants were identified to have CP of whom 90.7% (n = 39) infants had global HINE score <66 (sensitivity 90.7% and specificity: 97.8%). Conclusion: Despite study attrition and the impact of COVID-19, it was feasible to collect GMA videos in inpatient setting and infants at risk of CP were diagnosed as early as 12 months in a LMIC. Use of the structured risk factor questionnaire and adherence to best practice guidelines ensured a highly sensitive screening process and diagnostic outcomes. Our interim findings demonstrate the scope of this simple and scalable protocol in supporting clinicians for the early identification of infants with CP to facilitate early intervention and shared decision-making with families for best outcomes in LMICs.

CIRCULATING CELL-FREE DNA IS A BIOMARKER OF PREMATURE BIRTH AND COVID-19 AND PREDICTS PRENATAL CEREBRAL ISCHEMIA IN NEWBORNS

Circulating cell-free DNA is a possible marker of not only apoptosis, but also COVID-19 in pregnant, which can also be a trigger factor for premature birth and predicts prenatal hypoxic-ischemic encephalopathy injury in newborns. DNA fragmentation in tissues and blood plasma was measured with the diphenylamine assay. The material for the study was the peripheral blood from pregnant women and newborns, cord blood, tissue of the placenta. A comparison of the level of cfDNA in the serum of healthy pregnant and pregnant women with premature birth suggests a high level of it in women with premature birth. Pregnant women with COVID-19 had significantly higher cfDNA values as compared to those in healthy pregnant women in cord blood, placenta and in newborns from women with COVID-19. The level of cfDNA increased with the severity of neonatal hypoxicischemic encephalopathy injury in newborns from women with premature birth.

Neuroimaging findings in hospitalized patients with COVID-19

Background: Variable neuroimaging findings have been reported in patients with coronavirus disease 2019 (COVID-19). In addition to respiratory symptoms, many neurologic manifestations of COVID-19 are increasingly reported and variable neuroimaging findings have been observed in patients with COVID-19. Our aim was to describe findings observed in hospitalized patients with COVID-19, presenting with acute neurologic manifestations and undergoing computed tomography (CT) or magnetic resonance imaging (MRI) of the brain. Methods: We performed a retrospective study involving patients with laboratory-confirmed SARS-COV-2 infection, admitted to our hospital between July 1 and December 30, 2020. Patients who presented with acute neurologic symptoms and required neuroimaging were only included in the study. Neuroimaging examinations were evaluated for the presence of, infarction, hemorrhage and encephalopathy. The frequency of these findings was correlated with clinical variables, including presence of comorbidities, requirement for intensive care unit admission, and duration between admission and onset of neurologic signs and symptoms as documented in the hospital medical records. Results: A total of 135 patients underwent at least one cross-sectional imaging of the brain, the median age of these patients was 63 years, and 72% were men. Disturbed level of consciousness was the most common neurologic symptom (80.7%). Acute neuroimaging findings were found in 34 patients (25.2%) including;acute ischemic infarcts (16/135;11.9%), intracranial hemorrhages (9/135, 6.7%), cerebral venous thrombosis (2/135;1.5%), posterior reversible encephalopathy syndrome (1/135;0.7%), and hypoxic-ischemic encephalopathy (6/135, 4.4%). There was no statistically significant difference in patient age (p = 0.062), sex (0.257), presence of comorbidities (p = 0.204), intensive care unit admission (p = 0.326) and duration between admission and onset of neurologic signs and symptoms (p = 0.755), in patients with positive versus negative neuroimaging studies. Conclusions: Our study showed that cerebrovascular complications, ischemic and hemorrhagic were the most frequent imaging finding in hospitalized patients with COVID-19. Knowledge about these potentially serious complications can help optimize management for these patients.

Cerebrovascular injury associated with COVID-19 and non-COVID-19 acute respiratory distress syndrome

Background: Neurologic complications of Coronavirus Disease 2019 (COVID-19) may be associated with neurotropism of the virus or secondary brain injury from systemic inflammation. Acute respiratory distress syndrome (ARDS) is associated with cerebrovascular injury, including both ischemia and hemorrhage. We aimed to compare brain MRI findings of COVID-19 associated ARDS with non-COVID-19 ARDS. Methods: A registry of patients with COVID-19 from March 2020 through July 2021 from a hospital network was reviewed. Patients who met criteria for ARDS by Berlin definition and underwent MRI during their hospitalization were included. These patients were matched 1:1 by age and sex with patients who underwent MRI from another registry of patients of ARDS in the same hospital between 2010 and 2018. Cerebrovascular injury was classified as either acute cerebral ischemia (ischemic infarct or hypoxic ischemic brain injury) or intracranial hemorrhage (ICH) including intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma, and cerebral microbleeds (CMBs). Results: Of 13,319 patients with COVID-19 infection, 26 patients had ARDS and MRI. Sixty-six of 678 non-COVID-19 ARDS patients had an MRI and were matched 1:1 by age and sex resulting in 23 matched pairs. The median age was 66 and 59% of patients were male. Patients with COVID-19 ARDS were more likely to have hypertension and chronic kidney disease but otherwise baseline medical characteristics were similar. ARDS severity as determined by PaO2/FiO2 ratio at ICU admission was similar between both groups. No difference was seen in the prevalence of cerebrovascular injury (52% vs 61%, p=0.8), cerebral ischemia (35% vs 43%, p=0.8), ICH (43% vs 48%, p=1.0), or CMBs (43% vs 39% p=1.0) on MRI between the COVID-19 and non-COVID-19 cohorts. However, two unique patterns of injury were seen only among COVID-19 patients: hemorrhagic leukoencephalitis (3 patients, 12%) and bilateral cerebral peduncular ischemia with microhemorrhage (2 patients, 8%). Conclusion: Cerebrovascular injury was common in both COVID-19 and non-COVID-19 ARDS without significant frequency difference. However, COVID-19 ARDS had unique neuroimaging patterns that may indicate distinct patterns of brain injury of COVID-19.

Review of Unrelated Donor Cord Blood Transplantation in Children over the Past 3 Decades

Four decades ago, Hal Broxmeyer demonstrated that umbilical cord blood (CB) contained hematopoietic stem cells (HSC) and hypothesized that CB could be used as a source of donor HSC for rescue of myeloablated bone marrow. In 1988, Gluckman et al reported the first successful cord blood transplant (CBT) of a child with Fanconi Anemia using matched sibling CB. This patient survives and 35 years later still has durable hematopoiesis from the CB donor graft. In 1991, Rubinstein et al established an unrelated donor (UD) CB bank and in 1993 the first UD CBT was using a unit from this bank. Since that time, >40,000 CBTs have been performed worldwide. We hypothesized that changes in cord blood banking (increased size, diversity, and quality of banked units enabling selection of units with higher cell doses and closer HLA matching) and in transplantation (less use of steroids, availability of newer therapies for prophylaxis and treatment of graft versus host disease [GVHD], improved antifungal and antiviral detection and therapeutics) have improved outcomes of CBT today. To address this hypothesis, we performed a retrospective study combining data from Eurocord and Duke University in a large cohort of children transplanted with a single UD CB unit (CBU) from 1993-2019. Standard transplant outcomes (overall survival [OS], disease free survival [DFS], acute and chronic GVHD, treatment related mortality [TRM], and relapse) and changes in outcomes over 3 time periods (1:<2005, n=1297;2:2005-2010, n=1735;and 3:>2010, n=1802) were studied. Relative contributions of cell dose and HLA matching to transplant outcomes over time were assessed. A total of 4834 patients (4015 from Eurocord and 819 from Duke) were analyzed. The majority of patients, (59%, n=2839) had malignant diagnoses including 1422 with ALL, 887 with AML and 167 with MDS. Of the 1995 with non-malignant diagnoses, 761 had inborn errors of metabolism, 644 had primary immunodeficiency, 325 had a bone marrow failure syndrome and 206 had a histiocytic disorder. Half of the patients had positive serologies for CMV prior to transplant. The median age of the cohort fell from 5.2 to 3.25 years over time. In patients with malignancies, use of total body irradiation decreased over time. The median total nucleated cell (TNC) and CD34+ cell doses administered were 8.07x10e7 and 6.17x10e5 cells/kg and increased over time. HLA matching and transplantation of patients in earlier disease states also increased over time, p<0.001 for both. The probability of 5-year OS in the entire cohort was 53.48% and improved over time: 42%;57.4%;and 60.4%, in periods 1,2,3 respectively (p<0.0001). OS improved with closer HLA matching, higher cell dose, myeloablative conditioning, and negative pre-transplant CMV serologies. For patients with malignancies, DFS increased and TRM and acute GVHD decreased over time. In contrast, leukemic relapse did not change throughout the years. OS was higher in patients with inborn errors of metabolism and also improved over time with 57.8% surviving before 2005, 69.4% from 2005-2010, and 71% after 2010 (p=0.0141). Similar results were seen in the cohort with immune deficiencies. In the entire cohort, the median time to neutrophil engraftment decreased from 25 days (period 1) to 19 days (period 3). In multivariate analysis for engraftment, a higher TNC dose (p=0.001) up to but not beyond the median cell dose (8.07x10e7 cells/kg), total body irradiation, and the use of ATG improved engraftment. Acute GVHD decreased from 35% before 2005 to 27.1% after 2010 (p=0.0556) while the incidence of chronic GvHD was stable. The use of ATG reduced the risk of acute GVHD and closer HLA matching reduced the risk of both acute and chronic GVHD. In this population of patients receiving high cell doses, outcomes were predominantly influenced by HLA matching and increasing cell dose did not abrogate HLA mismatching. In conclusion, we analyzed the largest cohort of pediatric patients undergoing CBT over the past 3 decades. OS, DFS and engraftment have improved over time accompanied b decreases in TRM and acute GVHD. Relapse and chronic GVHD were stable and remain low. These improvements are explained by the increased availability of high quality banked CBUs enabling selection of closer HLA matching and units with higher cell doses. The numbers of CBTs have decreased in the past decade, but these results support the ongoing use of CBT in children lacking matched related or unrelated donors. [Formula presented] Disclosures: Kurtzberg: Neurogene: Consultancy;CryoCell: Patents & Royalties: Duke licensed IP, and data and regulatory packages for manufacturing and use of cord blood and cord tissue MSCs in the treatment of patients with hypoxic ischemic encephalopathy, cerebral palsy, autism, acute ischemic stroke, COVID-ARDS, and COVID-MIS-C.;Sinocell: Patents & Royalties: Duke licensed IP, data, and regulatory packages for use of autologous and sibling cord blood to treat children with cerebral palsy.;Celularity: Current holder of stock options in a privately-held company. Troy: SinoCell: Patents & Royalties;CryoCell: Patents & Royalties;Bristol Myers Squibb: Research Funding;Synthetic Biologics: Honoraria;Gamida Cell: Consultancy;The EMMES Corporation: Consultancy;The Community Data Roundtable: Consultancy;AegisCN: Consultancy.

Radiographic and clinical neurologic manifestations of COVID-19 related hypoxemia.

The novel coronavirus SARS-CoV-2 is known to cause hypoxemia and acute respiratory distress syndrome (ARDS) in a significant portion of those with severe disease. Survivors of critical illness and ARDS often experience neurocognitive impairment but, to date, there is scant literature correlating radiographic hypoxic brain injury to hypoxemia related to ARDS. In this case series, we describe three cases of hypoxic brain injury seen on magnetic resonance imaging (MRI) in patients with hypoxemia secondary to COVID-19-related ARDS. The lack of severe observed hypoxemia in two of the cases suggests that unrecognized or asymptomatic hypoxemia may play a role in hypoxic brain injury related to COVID-19.