Factors Associated with Hospitalization with Symptomatic Coronavirus Disease 2019 among Pregnant Individuals: A Multicenter Retrospective Cohort Study

Background: Pregnant individuals are at increased risk of coronavirus disease 2019 (COVID-19) hospitalization and death, and primary and booster COVID-19 vaccination is recommended for this population. Method(s): Among a cohort of pregnant individuals who received prenatal care at 3 healthcare systems in the United States, we estimated the cumulative incidence of hospitalization with symptomatic COVID-19 illness. We also identified factors associated with COVID-19 hospitalization using a multivariable Cox proportional hazards model with pregnancy weeks as the timescale and a time-varying adjustor that accounted for severe acute respiratory syndrome coronavirus 2 circulation;model covariates included site, age, race, ethnicity, insurance status, prepregnancy weight status, and selected underlying medical conditions. Data were collected primarily through medical record extraction. Result(s): Among 19 456 pregnant individuals with an estimated due date during 1 March 2020-28 February 2021, 75 (0.4%) were hospitalized with symptomatic COVID-19. Factors associated with hospitalization for symptomatic COVID-19 were Hispanic ethnicity (adjusted hazard ratio [aHR], 2.7 [95% confidence interval {CI}, 1.3-5.5]), Native Hawaiian or Pacific Islander race (aHR, 12 [95% CI, 3.2-45.5]), age <25 years (aHR, 3.1 [95% CI, 1.3-7.6]), prepregnancy obesity (aHR, 2.1 [95% CI, 1.1-3.9]), diagnosis of a metabolic disorder (aHR, 2.2 [95% CI, 1.2-3.8]), lung disease excluding asthma (aHR, 49 [95% CI, 28-84]), and cardiovascular disease (aHR, 2.6 [95% CI, 1.5-4.7]). Conclusion(s): Although hospitalization with symptomatic COVID-19 was uncommon, pregnant individuals should be aware of risk factors associated with severe illness when considering COVID-19 vaccination. Copyright © 2022 Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Lifestyles in adults in total quarantine and partial quarantine, during the COVID-19 pandemic

The pandemic containment strategy implemented in the country in its first months considered keeping the population in preventive quarantine, either total (CT) or partial (CP). The study aimed to determine the differences and similarities between the lifestyles (EV) of adults in CT and CP, during the COVID-19 pandemic. A comparative cross-sectional descriptive study was carried out. Four hundred adults from country ' s central zone, aged between 20 to 59 years were selected with a non-probabilistic sampling for convenience using different virtual communication networks. The EV were assessed by the FANTASTIC Questionnaire. Student's t-test and Mann-Whitney U test were used to compare the CT and CP groups;and Cohen's d to measure effect size. The main results were that both groups reported moderate and high levels of EV, highlighting the total absence of Dangerous EV. In comparative terms, the CP group presented better EV scores in general and at a specific level in the domains of Associativity and physical activity, Nutrition, Tobacco, Alcohol and other drugs, Sleep and stress, Insight and Other behaviors;all with a small effect size. It is conclud-ed that adults in PC have healthier EV than those in CT. It is deduced that the conditions proposed by CT negatively affect healthy EV in adults.

Gender inequalities in a tourist region: the case of the Canary Island companies in a pre-pandemic scenario

The Canary Islands conform the most populated ultra-peripheral region of the European Union with almost two million inhabitants, receiving more than 13 million tourists in 2019, in a pre-pandemic scenario. Therefore, the islands represent a very particular setting to explore the impact of the global pandemic in business in general, and also in gender diversity and the situation of women on corporate boards in particular. Firms from several industries were observed in detail, as retail, wholesale, construction, manufacturing, repair and sale of vehicles and accommodation. The study explores the setting just before the advent of the coronavirus to their lives in a region which is obviously highly fragile to these events. The study reveals huge gaps in gender equality, with women less present and with less executive power than men, particularly in companies with better results and from certain industries, which confirms previous stereotypes. Further research will be required by means of longitudinal studies. © 2022 Institution for Marine and Island Cultures, Mokpo National University.

Drafting e-commerce regulations for a sustainable economic recovery: Lesson from DEPA analysis

The current international pandemic situation caused by the COVID-19 outbreak has disrupted economic activity and development worldwide. However, digital enabled activities have proven a relative stronger resilience, and, worldwide, most economic sectors have shifted to digital platforms to continue operating. In this context, the drafting of digital economy regulations has become a relevant policy issue for governments across the Asia Pacific region. Nevertheless, the absence of multilateral regulations in this area has become an obstacle for achieving common regulatory frameworks to deal with digital economy issues, for which regional and bilateral agreements have begun to draft regulations. The proliferation of digital economy provisions in preferential agreements may lead to the so called "spaghetti bowl”. From here, the objective of this paper is to contribute to the governance of digital economy among APEC economies, through the characterization of free trade agreements signed between APEC and Latin American economies. This selection was made due to the diversity of agreements that can be found within this subregion. In this context, the Digital Economy Partnership Agreement (DEPA), led by Chile, New Zealand, and Singapore has become a reference point that could serve as a steppingstone towards common regulatory frameworks in this matter. The paper concludes that DEPA may be used as a benchmark for the development of regulations that will help boost cross border e-commerce in APEC economies for a post pandemic sustainable recovery. © 2022, University of Passo Fundo. All rights reserved.

Riding the Waves: Infection by SARS-CoV-2 Variants in Solid Organ Transplant Recipients at Texas Children's Hospital

Background. Texas Children's Hospital is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exist about SARS-CoV-2 infection (COVID-19) in the pediatric SOT population. We evaluated the impact of different SARS-CoV-2 variants in a cohort of PCR positive SOT recipients. Methods. SOT recipients with a positive SARS-CoV-2 PCR test from 3/1/2020 to 2/28/2022 were included in the cohort. The study period was divided into 3 eras based on the predominant circulating variant of SARS-CoV-2: 3/20-6/21 original strain/ Alpha, 7/21-11/21 Delta, and 12/21-2/22 Omicron variants. Retrospective medical record review was performed;Chi-squared and Fischer exact test were used to compare groups. Results. A total of 269 of 1031 (26%) SOT recipients tested positive for SARS-CoV-2 during the study period. By organ, 87/335 (26%) heart, 57/224 (25%) kidney, 92/405 (23%) liver, and 25/67 (37%) lung recipients had COVID-19 infection. By era, there were 99 (37%) original strain/ Alpha, 65 (24%) Delta, and 105 (39%) Omicron. The patients' median age was 12.72 years (IQR 6.6, 15.1) with a minority of recipients being female (42%). Common comorbidities included hypertension (50%), obesity (13%), diabetes (10%), and chronic kidney disease (10%);34% had no comorbidities aside from chronic immunosuppression post-transplant. Overall, 80% of recipients were symptomatic (Figure 1), and 50 (19%) required hospitalization. Hospitalization rates were highest (29%) during Delta, compared with 18% for original/ Alpha and 13% for Omicron (p=0.02) eras. Need for respiratory support, ICU admission, and all-cause mortality did not vary by era (Table 1). Three SOT recipients (2 original/Alpha and 1 Delta) were diagnosed with multi-inflammatory syndrome in children (MIS-C). Conclusion. Our study suggests that pediatric SOT recipients have a high risk for hospitalization and short-term complications with COVID-19;Omicron appears to cause less severe disease, including MIS-C. Additional studies are needed to understand long-term complications of COVID-19 in SOT recipients.

The MET Project: Distinguishing Multisystem Inflammatory Syndrome in Children from Typhus Using Artificial Intelligence

Background. Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection shares features with other inflammatory states, notably Kawasaki Disease. The rickettsial infection murine typhus is also in the differential for MIS-C in endemic areas. As the therapeutic approaches differ, it is essential to distinguish these disorders soon after presentation, well before confirmatory serologic testing results. Our objective was to develop an algorithm to accurately predict MIS-C versus typhus. Methods. Retrospective review extracted demographic, clinical, and laboratory features available within 6 hours of presentation for 133 MIS-C and 87 typhus patients. 33 features were broken into 44 inputs and passed through an attention module to compute importance. Inputs were then entered into machine learning algorithms as MIS-C or typhus. Patients were divided into training and test cohorts respecting proportions in the dataset. An equation was built to calculate the 'MET' (MIS-C versus endemic typhus) score. Results. MIS-C patients were younger (8.4 v 11.2 years, p< 0.0001) and the majority (71%) presented on day 4-6 of fever;most typhus patients (84%) presented with >=6 days (mean 4.9 v 7.3 days, p< 0.0001). Typhus patients were more likely to have rash (86% v 51%, p< 0.0001) and MIS-C patients red eyes (71% v 36%, p< 0.0001), other features were similar. MIS-C patients had higher C-reactive protein levels (17.7 v 9.8 mg/dL), procalcitonin (14.0 v 0.48 ng/mL), fibrinogen (558 v 394 mg/ dL) and neutrophil-to-lymphocyte ratio (12 v 3.5), all p< 0.0001, other parameters were similar. MIS-C patients were also more likely to have elevated troponin (0.48 v 0.01 ng/mL, p< 0.0001) and require intensive care (66% v 6%, p< 0.0001). A long short term memory network outperformed 6 other models (99% accuracy using all 33 elements). The MET score predicted MIS-C versus typhus with 90% accuracy using only 10 features (sensitivity 90%, specificity 90%). Conclusion. The clinical and laboratory similarities between typhus and MIS-C present challenges, but they can be reliably distinguished using artificial intelligence with as little as 10 features. Our ongoing interprofessional collaboration aims to make the MET score readily available to clinicians for use in patient encounters.

Epidemiology of Chronic High Level (CHL) Epstein-Barr virus (EBV) DNAemia in Pediatric Solid Organ Transplant Recipients (SOTR) at Texas Children's Hospital (TCH)

Background: EBV infections cause significant morbidity and mortality in pediatric SOTR and can be complicated by post-transplant lymphoproliferative disorder (PTLD). Contemporary data on CHL EBV DNAemia and the development of PTLD are limited. Methods: A retrospective cohort study of patients ≤ 21 years of age who received heart, lung, liver, kidney, or multi-organ transplants at TCH between 2011–2018 was conducted. Primary outcome was CHL EBV DNAemia, defined as peripheral blood lymphocyte EBV values ≥ 500 copies/ug or whole blood EBV values ≥ 10,000 IU/mL for ≥ 6 months. Associations with CHL EBV DNAemia were measured using chi-squared or Fisher exact test and multivariate logistic regression. Time to CHL EBV DNAemia was assessed using Kaplan-Meier method. Results: Among 687 SOTR (152 heart, 87 lung, 259 liver, 175 kidney, 14 multi-organ), 87 (13%) developed CHL EBV DNAemia;this included 15 (9%) heart, 9 (10%) lung, 59 (22%) liver, 2 (1%) kidney, and 2 (14%) multi-organ recipients. Receiving a heart [OR 2.1, 95% CI (2.1 – 62.4)], lung [7.7, 95% CI (1.5 – 39.3)], liver [OR 31.8, 95% CI (4.9 – 208.7)], or multi-organ [OR 18.3, 95% CI (2.0 – 170)] transplant and being 1–5 years of age [OR 4.0, 95% CI (1.6 – 9.8)] were associated with CHL EBV DNAemia. SOTR transplanted from 2015–2018 were less likely to develop CHL EBV DNAemia than those transplanted from 2011–2014 [OR 0.5, 95% CI (0.3 – 0.8)]. EBV risk status, CMV risk status, gender, and induction therapy were not associated with developing CHL EBV DNAemia.The median maximum peripheral blood lymphocyte and whole blood EBV values for those with CHL EBV DNAemia were 9475 (993 – 258151) copies/ug and 22093 (564 – 550000) IU/mL, respectively. Organ transplanted (p< 0.01), age (p< 0.01), and EBV risk status (p< 0.01) were associated with time to CHL EBV DNAemia (Figure 1). PTLD occurred in 28 (4%) of SOTR;14 (50%) had preceding CHL EBV DNAemia (p< 0.01).Figure 1 Time to CHL EBV DNAemia. Conclusion: This cohort of pediatric SOTR demonstrates a low prevalence of CHL EBV DNAemia and PTLD. Receiving a heart, lung, liver, or multi-organ transplant and being 1–5 years of age were associated with developing CHL EBV DNAemia. SOTR who developed CHL EBV DNAemia were more likely to develop PTLD, suggesting that further interventions targeting this group may be warranted. Disclosures: Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support Elizabeth A. Moulton, MD, PhD, Pfizer: Co-investigator for SARS-CoV-2 pediatric vaccine trials.

Impact of Covid-19 on Youth's Trust in Institutions: The Case of Las Palmas de Gran Canaria

There is a considerable consensus on how youth´s trust in governments and institutions had decreased in recent years, in particular because of recurrent crisis. For that reason, the accumulation of empirical evidence is essential in this particular arena. In this article, derived from a project funded by the Department of Youth of the Municipality of Las Palmas de Gran Canaria, the level of trust of youth in the institutional framework will be analysed both in the pre-pandemic and in the post-pandemic times at the Municipality of Las Palmas de Gran Canaria, the most populous urban area in the Canary Islands and the Macaronesia. With this goal, data have been obtained from two surveys (one pre-pandemic and the other post-pandemic) and subsequently, it has been developed an analysis of principal components and explanatory factors, taking into account different socio-demographic variables (sex, age, social origin, educational level, employment situation) in order to assess how the institutional trust of youth is affected by these variables both before the pandemic and after it. © 2022 RESTORATIVE JUSTICE FOR ALL.

Academic Satisfaction of Pedagogy Students Regarding Learning in Virtual Mode

The Covid-19 pandemic in Chile was declared as such in March 2020. As a result, the Ministry of Education compiled guidelines to provide continuity to the formative processes, through which the concept of remote learning emerged. This research paper aims at identifying academic satisfaction of pedagogy students in a higher education institution (HEI) regarding learning in the virtual mode in the pandemic context. A quantitative, non-experimental, cross-sectional methodology was used. The sample consisted of 337 students in 6 pedagogical courses at an HEI in the Araucanía region to whom a questionnaire on satisfaction with virtual teaching was administered. Results indicated that student satisfaction was low regarding the way content was handled and evaluation mechanisms used in the virtual mode. However, high satisfaction was shown in the items corresponding to teacher-student interaction. In addition, we found no statistically significant differences in the items related to the fulfillment of expectations and learning achieved in the virtual mode, either by gender, level of study, program, or academic performance. Finally, there was high dissatisfaction with virtual teaching during the present academic cycle. We recommend the systematic evaluation of the indicators of educational quality, mainly linked to the treatment of the content, the evaluation mechanisms used, and the teacher-student interaction channels, since they improve the academic performance of HEIs. © Authors.

Remdesivir in the treatment of children 28 days to < 18 years of age hospitalised with COVID-19 in the CARAVAN study

P168 Table 1Overall safety showing proportion of participants with AEsParticipants, n (%) Cohort 1n=12 Cohort 2n=12 Cohort 3n=12 Cohort 4n=12 Cohort 8n=5 TotalN=53 Any AE 11 (92) 7 (58) 9 (75) 7 (58) 4 (80) 38 (72) Grade ≥3 AE 6 (50) 2 (17) 1 (8) 4 (33) 2 (40) 15 (28) SAE 5 (42) 2 (17) 0 3 (25) 1 (20) 11 (21) Treatment discontinuation due to AE 2 (17) 0 0 0 0 2 (4) Treatment-emergent death 1 (8) 1 (8) 0 0 1 (20) 3 (6) Grade 3–4 laboratory abnormalities 9 (75) 2 (17) 4 (33) 4 (36) 3 (60) 22 (42) ConclusionsRDV was generally well tolerated in children hospitalised for COVID-19 who were 28 days and older, weighing at least 3 kg. No new safety trends for RDV were identified and a high proportion of participants had clinical improvement. CARAVAN is ongoing for enrolment of full term and preterm neonates.

A New Chapter in an Evolving Pandemic: Successful Pediatric Liver Transplantation with COVID+ Donors

Purpose: We report the first two pediatric liver transplants utilizing allografts from COVID+ donors, infected at time of organ procurement, demonstrating a pivotal step toward donor pool maximization amid a viral pandemic with poorly understood transmissibility in the pediatric patient. Method(s): This is a prospective and retrospective review of two pediatric liver transplants and their donors who tested positive for SARS-CoV-2 at time of procurement. Data was obtained through the electronic medical record system and UNet DonorNet platform. Result(s): The first donor is a 3-year-old male succumbing to head trauma. 1 of 5 nasopharyngeal swab RT-PCR tests demonstrated COVID-19 positivity while 1 of 3 bronchoalveolar lavage RT-PCR tests indicated SARS-CoV-2 infection. Preceding procurement in the second donor, a 16-month-old male with unknown etiology of cardiorespiratory arrest, 2 nasopharyngeal swab RT-PCR tests and 1 bronchoalveolar lavage RT-PCR test failed to detect SARS-CoV-2 infection. Diagnosis was not made until the Medical Examiner's office repeated a nasopharyngeal swab RT-PCR and archive plasma RT-PCR which were both positive for SARS-CoV-2. The two 2-yearold pediatric liver recipients underwent transplantation in November 2021. Continued follow-up demonstrates successful transplant void of viral transmission or hepatic artery thrombosis as liver chemistries have anticipatorily normalized with excellent graft function. One recipient experienced early portal vein thrombosis treated by interventional radiology with discharge on postoperative day 20. Conclusion(s): This report is the first to describe successful pediatric liver transplants from COVID+ donors. This data reinforces case reports in the adult transplant population of successful use of COVID + donor organs and further supports the judicious use of COVID+ donors for extrapulmonary pediatric organ transplant. The concern for donor-derived transmission must now be weighed against the realized benefit of successful, life-saving transplantation for end stage liver disease in the pediatric patient. (Figure Presented).

A HIGH-THROUGHPUT MULTIPLEXED MICROFLUIDIC DEVICE FOR COVID-19 SEROLOGY ASSAYS

The need to develop high-throughput diagnostic platforms for infectious diseases has never been more evident than with the emergence of SARS-CoV-2 and the ensued COVID-19 pandemic. Microfluidics, in tandem with its multiplexing capabilities, high sensitivity, and potential for automation, provides a unique advantage towards the development of high-throughput serological diagnostic platforms. Here, we present a microfluidic device that detects IgG or IgM raised against four SARS-CoV-2 antigens (spike, S;S1 subunit, S1;the receptor-binding domain, RBD;and nucleocapsid, N) from 50 serum samples in parallel. We validated the platform with a cross-sectional cohort of 66 samples from confirmed COVID-19 patients and a pre-pandemic control of 34 serum samples collected in 2018. The analysis of both antibodies against all four viral antigens provided a sensitivity of 90.4% and a specificity of 94.1%, with both parameters increasing to 100% in late-stage samples (21-30 days after symptoms onset). We expect our device to open the door to massive serological testing, impacting diagnostics, vaccine development, and epidemiological understanding of COVID-19. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

Nutritional status, level of physical activity and eating habits, in university students from the Maule Region during the COVID-19 pandemic period

The present study aims to determine the eating habits, nutritional status and level of physical activity in pandemic period of university students in the Maule Region. It corresponded to a descriptive, cross-sectional, non-experimental quantitative approach. The population was made up of 1.253 young adults (21.22??2.27 years) who are studying between the first and last year of undergraduate university. Two questionnaires were applied: National Health Survey (Chile) and International Questionnaire of Physical Activity (IQPA). Regarding the results, it was observed that: on average the entire sample increased two kilograms of body weight compared to the pre-pandemic period. Regarding the level of physical activity and in relation to the MET??S spent by both men and women, they do not reach the minimum weekly recommendations. In addition, women reported a higher prevalence of sedentary lifestyle. Students during the period of confinement as a result of the pandemic, report good eating habits, most of them have a normal nutritional status (BMI) and regarding the level of physical activity, a high percentage does not reach the minimum recommendations established by the WHO.

A Simulated Hospital in a COVID-19 Pandemic Environment for Undergraduate Neurology Students

Objective: To determine the impact of a simulated hospital on a neurology clerkship of 5-year medical students during the coronavirus pandemic in Bogota, Colombia. Background: The COVID-19 pandemic has led to the disruption of all sectors of the economy including education. According to UNESCO, over 1.37 million young people, including medical students, were affected by the closure of the education system. The main challenge for medical education has consisted in offering clerkships within a biosafety environment. The simulated hospital emerges as a teaching tool that guarantees the development of medical skills in a biosafety environment. Design/Methods: A quasi-experimental design was conducted in a population of 5th-year medical students during their neurology clerkship. Our sample comprised two similar groups, one received a traditional face-to-face format during 2019, whereas the second group received a mixed virtual and simulation-based clerkship in 2020. All students in the pandemic group answered a Likert scale survey regarding their satisfaction with the simulated hospital. To evaluate theoretical knowledge acquisition students of both groups were required to perform a mid-term and a final examination. Results: Most of the students considered the simulated hospital a useful addition that should be incorporated into their medicine curriculum regardless of the pandemic. From the results, it is clear that students perceived that exposure to a simulated hospital facilitated their learning process (93.1%) and allowed greater interaction with the teacher compared to a face-to-face environment (77.3%). The difference in test results was not clinically significant. Conclusions: Our study shows that a simulated hospital is a highly efficient method to acquire clinical skills in trainees with improvement in medical knowledge and satisfaction evidenced by the Likert scales and comparable results in academic evaluations. Our experience indicates that exposure to a simulated hospital should be integrated into the curricular milestones of the medical education program regardless of the pandemic.

Adaptation and development of IR services in response to the COVID-19 pandemic: preliminary results of a focused survey

Purpose: The cyclic nature of active and recovery phases of the COVID-19 pandemic, has demanded fast adaptations and preparation for health care workers world-wide. We aimed to assess how interventional radiologists are handling the pandemic during active and recovery phases with regard to work and team structures, as well as mental health and how the pandemic could have increased the awareness of minimally-invasive therapies as alternatives to postponements of non-urgent procedures. Material and methods: 7125 CIRSE members were invited to participate. For this interim report, responses were collected between 23 November 2021 and 17 December 2021. Results: 114 responses were obtained for this preliminary report, of which 102 were complete. 94% (n=99) of respondents were interventional radiology specialists. Most respondents reported having established a routine to handle different waves of the pandemic (89.5%;n=102). Compared to active phases, fewer respondents indicated at least one pandemic-associated measure in their department during recovery phases (46%-71% vs 13%). 56% reported an increase in ambulatory care patients either during active and/or recovery phases. 54% reported more referrals during active and/or recovery phases. 25% reported increased hours at the hospital during recovery phases, 52% indicated increased sick leave, care leave, quarantine, and burn-out of team members and only 39% reported to get enough time to rest during recovery phases. Conclusion: While the COVID-19 pandemic is continuing to burden IR departments and the mental health of IRs, more than half of respondents reported an increase in referrals for minimally-invasive therapies and ambulatory care.

Impact of the COVID-19 pandemic on rheumatology nursing consultation

Objective: The COVID-19 pandemic has brought major changes to the model of patient care in Rheumatology. Our aim was to compare the change in the care delivered in a rheumatology nursing consultation before and during the pandemic.& nbsp;Material and methods: Descriptive and observational study. Patient care was registered before and during the COVID-19 outbreak. The variables collected were age, sex, prevalent rheumatic disease, type of visit and reason for consultation.& nbsp;Results: 254 consecutive patients were included before the COVID-19 pandemic for 20 days and 251 patients during COVID-19 for 10 working days. The mean age was 61 years before and 57 during the pandemic. Of both groups, 74% were women. The most frequently attended pathologies before and during COVID-19 were rheumatoid arthritis and spondyloarthropathies. Scheduled face-to-face visits decreased during COVID-19 (46.5% versus 1.6%), with an increased number of phone scheduled visits (2.8% versus 52.2%) and spontaneous consultations either by phone or e-mail (28.3% versus 45%). The type of scheduled visits during COVID-19 were for stable diseases (20% versus 37%) and monitoring (12% versus 38%). The reason for spontaneous consultation increased during COVID-19 and were mainly doubts regarding prevention measures and treatment optimization (13.8% versus 31.1%).& nbsp;Conclusions: The first wave of COVID-19 brought to rheumatology nursing consultation a global increase in all activities in the number of visits per day, in the number of stable patient controls, in monitoring and answering patient concerns. (C)& nbsp;2021 Published by Elsevier Espa?a, S.L.U.

REMDESIVIR TREATMENT for COVID-19 in HOSPITALIZED CHILDREN: CARAVAN INTERIM RESULTS

Background: Remdesivir (RDV) has been shown to shorten time to recovery in hospitalized adults with COVID-19. Some children who develop COVID-19 require hospitalization. Here we characterize the safety profile of RDV in 53 pediatric patients age 28 days to <18 years and describe clinical and virologic outcomes. Methods: CARAVAN (NCT04431453) is an ongoing open-label, single arm study of RDV in hospitalized patients <18 years with PCR-confirmed COVID-19. IV RDV was given for up to 10 days: 200mg on Day 1 followed by 100mg daily in Cohort 1 and 8 (<18y, weight ≥40kg) or 5mg/kg on Day 1 followed by 2.5mg/kg daily in Cohorts 2-4 (28 days to <18y, stratified by weight). Safety was assessed by adverse events (AEs) and lab tests (hematology, chemistry, urine, inflammatory, coagulation). Clinical outcomes included improvement on a 7-point ordinal scale, time to discharge, and oxygenation modality. Virologic outcomes included days to confirmed negative SARS-CoV-2 PCR (defined as 2 consecutive negative results). Results: At enrollment, median (IQR) age was 7y (2, 12) and weight was 24.6 (12.8, 55.1) Kg, 57% were female, 76% required supplemental oxygen, including 23% on invasive ventilation and 34% on high-flow oxygen (Table). Median number of RDV doses was 5 (4,8). Most patients (72%) experienced ≥1 AE;most common was constipation (17%). Serious AEs were reported for 21% of patients and none were study-drug related. Two patients with baseline transaminitis had non-serious AE of increased ALT contributing to premature discontinuation. Two patients died within the 30-day study period. Grade ≥ 3 lab abnormalities were reported in 42%;most common being decreased haemoglobin (n=9) and decreased eGFR levels (n=7). No safety trends related to RDV were apparent. In total, 85% showed clinical improvement on the 7-point ordinal scale by last assessment. Median (IQR) time to discharge was 8 (5, 17) days. By last assessment, 8% required supplemental oxygen, all of whom were invasively ventilated. Time to confirmed negative SARS-CoV-2 PCR CoV-2 PCR was 5 and 7 days from nasal/oropharyngeal samples in cohort 2 and 3, respectively, and not estimable in the other cohorts. Conclusion:RDV was safe and well tolerated among children 28 days to <18y treated for COVID-19. Overall, no safety trends for RDV were apparent and a high proportion, 85%, had clinical improvement. The study is ongoing with enrolment of full term and preterm neonates pending dose determination.

SARS-CoV-2 Infection in Solid Organ Transplant Candidates and Recipients at Texas Children's Hospital: A Retrospective Review

Background. Texas Children's Hospital (TCH) is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exists about SARS-CoV-2 infection (COVID-19) in the pediatric SOT populations. We evaluated the impact of COVID-19 in a cohort of PCR positive SOT candidates and recipients. We hypothesized that COVID-19 would more severely impact SOT recipients compared to transplant candidates. Methods. Patients with SOT or transplant candidates at TCH with a positive SARS-CoV-2 RT-PCR test since March 1, 2020 to April 12, 2021 were included in the cohort. Retrospective medical record review was performed, and descriptive statistics were used. Results. A total of 103 SOT patients were identified, 13 candidates and 90 recipients. Of the SOT candidates, there were 1 heart, 3 kidney, and 9 liver transplant candidates. The SOT recipient cohort included 33 heart, 6 lung, 20 kidney, 33 liver and 2 multi-visceral recipients. A significant difference in age was observed between candidates and recipients with candidates being younger with median age of 4.5 years as opposed to recipient's median age of 12.8 years (p=0.0003). The majority of patients, 70 of 101 (69%), were symptomatic. Most common symptoms reported were fever in 34/70 (49%), cough in 31/70 (44%), and headache in 19/70 (27%). A higher percentage of candidates (31%, 4 of 13) were hospitalized for acute COVID-19 infection compared to (17%, 15 of 90) of recipients. A transplant candidate who ultimately died from underlying illness and COVID-19 was the only patient in the cohort who required mechanical ventilation. More deaths (2/13, 15%) occurred in transplant candidates with COVID-19 compared to transplant recipients with COVID-19 (1/90, 1%, p=0.04);however, 2 of the deaths occurred after recovery from acute COVID-19 illness. Conclusion. Our study suggests that pediatric candidates who are actively listed for transplant with underlying conditions have more severe acute COVID-19 illness than pediatric SOT recipients despite their immunosuppression based on the higher mortality observed in the transplant candidates. Prospective studies are needed to better understand which specific patients are at increased risk for mortality from COVID-19.

Performance of the Brighton Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C) among a Large Single Center Cohort

Background. Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, life-threatening, hyperinflammatory condition presumed to follow SARS-CoV-2 infection. Whether MIS-C can also follow SARS-CoV-2 vaccination is not clear, making MIS-C an adverse event of special interest following immunization. Monitoring for post-vaccine MIS-C is complicated by the clinical overlap of MIS-C with numerous other inflammatory conditions including Kawasaki Disease, toxic shock syndrome, and viral myocarditis. A case definition for MIS-C was recently created with the Brighton Collaboration (BC). We aimed to determine the performance of the BC MIS-C case definition among a large, single-center MIS-C cohort. Methods. Retrospective review was performed for the first 100 MIS-C cases at our institution (May 2020-February 2021). All cases met the Centers for Disease Control and Prevention (CDC) case definition. Data on age, presentation, laboratory results and cardiac studies were collected and used to determine cases that fulfilled the BC case definition for MIS-C (see figure). Case Definition: Definite Case Results. Of 100 children (age < 21 years) diagnosed with MIS-C using the CDC case definition, 93 patients also fulfilled the BC definition. All 100 patients had elevated laboratory markers of inflammation and positive SARS-CoV-2 antibodies. However, 1 patient was excluded for significant respiratory symptoms (pulmonary hemorrhage), 5 were excluded due to only 1 clinical feature, and an additional patient was excluded for having none of the measures of disease activity. Among the 93 patients fulfilling the revised case definition, 88 (95%) met criteria for a definite case. Five of the 93 patients (5%) were considered probable cases, 1 reported only 1 day of fever and 4 had only 1 measure of disease activity. Conclusion. The original case definitions for MIS-C were created rapidly following the first emerging reports of this hyperinflammatory state. Knowledge of the varied clinical presentations of this disorder has grown substantially. Modification of the case definition to include features truly representative of MIS-C will allow for more precise diagnosis in the face of conditions which mimic MIS-C, and for accurate and reliable monitoring for adverse events following immunization.

Convalescent Plasma in Hospitalized Pediatric and Obstetric patients with COVID-19

Background. Published data on COVID-19 convalescent plasma (CCP) use in children and obstetric patients is limited. We describe a single-center experience of hospitalized patients who received CCP for acute COVID-19. Methods. We performed a retrospective review of children 0-18-years-old and pregnant patients hospitalized with laboratory-confirmed acute COVID-19 who received CCP from March 1st, 2020 to March 1st, 2021. Clinical and laboratory data were collected to assess the safety of CCP administration. Antibodies to SARS-CoV-2 were measured before and at various timepoints post CCP transfusion. Correlation between SARS-CoV-2 immunoglobulin administered versus the SARS-CoV-2 anti-Spike immunoglobulin response in patient serum was assessed. Results. Twenty-two children and 10 obstetric patients were eligible. 12 pediatric and 8 obstetric patients had moderate disease and 10 pediatric and 2 obstetric patients had severe disease. 5 pediatric patients died. 18/37 (48.6%) CCP units that were measured met FDA criteria for a high IgG titer. There were no complications with transfusion based on CDC, NHSN Biovigilance Component: Hemovigilance Module Surveillance Protocol. Two pediatric patients had fevers a few hours after CCP with low suspicion for a transfusion reaction. Median SARS-CoV-2 anti-spike antibody levels of pediatric patients post-transfusion for 0-7 days was 80.6AU/mL (range: 2-1070), 8-21 days was 180AU/mL (range: 12-661) and >21 days was 210AU/mL (range: 4.1-1220). For obstetric patients, post-transfusion antibody levels were only obtained 0-7 days post-transfusion with median 45AU/mL (range: 9.5-100). High-titer CCP showed a positive correlation with rise in patient immunoglobulin levels only in the obstetric patients but not in pediatric patients. Conclusion. CCP was administered safely to our moderately to severely ill pediatric and obstetric patients. Among pediatric patients, the median serum antibody level increased over time after transfusion and suggested that CCP did not interfere with the endogenous antibody production. Antibody dose of high-titer CCP correlated with post-transfusion response in only obstetric patients. Randomized trials in pediatric and obstetric patients are needed to further understand how to dose CCP and evaluate efficacy.