Subjective impact of COVID-19 pandemic on youth with tic and OCD spectrum disorders

Objectives: This study investigated the perceived impact of the COVID-19 pandemic on youth with chronic tic disorders (CTD) and/or obsessive-compulsive disorder (OCD) based on subjective reports, objective measures, and parental feedback. This study also sought to investigate whether and how these reported experiences differed based on the presence of underlying tic and/or OCD spectrum diagnoses. Method(s): Children with CTD, OCD, and Tics + OCD and their parents were recruited to complete an online survey from July 2020 through April 2021. Forty-eight responses were received;child respondents had a median age of 12 years. Result(s): On average, youth reported that the pandemic negatively impacted them in several domains, particularly after-school activities, relationships with friends, and social/community gatherings. Despite the small sample size, youth with OCD appeared to experience a greater negative impact compared to other subgroups. Median screen use in this sample was 3-8 hours a day, and youth who reported > 8 hours on weekends trended towards increased depressive symptoms. Conclusion(s): Consistent with the physician-authors' clinical experiences, youth with CTD, OCD, and Tics + OCD and their parents reported a subjective negative impact of the pandemic on various symptoms and psychosocial domains. Going forward, if another lockdown loomed, it would be valuable to stay attuned to these vulnerable youth, particularly those with OCD symptoms, and consider providing support in specific psychosocial domains, such as relationship with peers and home life.Copyright © 2023 Elsevier Inc.

Retour d'expérience de deux structures d'urgences de centres hospitaliers généraux pendant la crise de la Covid-19

La Covid-19 s'est abattue sur l'Alsace en quelques jours, mettant à mal les hôpitaux de Mulhouse et de Colmar. Bien que proches, des différences notables existent au sein de ces deux structures en termes architecturaux et de ressources humaines. Comment cette vague a-t-elle modifié les organisations de chacun ? Quelles alternatives ont pu être mises en place ? Après la présentation de chaque site sont analysées les adaptations nécessaires afin d'absorber les flux de patients et leur proposer une prise en charge décente malgré des conditions parfois très dégradées. Nouvelles filières, modifications organisationnelles, renforts de personnel en interne puis en externe, augmentation capacitaire nette, recherches de solutions alternatives aux voies classiques d'approvisionnement des matériels… ont été une partie de la solution. Malgré les alertes du terrain, l'action nationale est restée en décalage de compréhension de la gravité de la situation locale, avec des recommandations et des actions soit inapplicables, soit trop tardives. Les établissements et professionnels de santé ont eu un sentiment d'isolement, renforcé par l'absence de représentant des tutelles et notamment de l'Agence régionale de santé sur le terrain. Deux éléments majeurs peuvent être mis en avant : une cohésion majeure de l'ensemble du centre hospitalier avec travail d'équipe et de terrain entre soignants et direction, et une implication de l'ensemble des acteurs de la médecine d'urgence (public, privé, libéraux, service départemental d'incendie et de secours) ;ils ont été les déterminants dans notre capacité à faire face à cet événement inédit.Alternate abstract: COVID-19 fell down on Alsace in few days, putting a strain on both hospitals of Mulhouse and Colmar. Although close, there are significant differences between these two structures in terms of architecture and human resources. How has this wave modified both organizations? After the presentation of each site, we analyzed the necessary adaptations made to absorb the flow of patients and offer them decent care despite sometimes very deteriorating conditions. New pathways, organization modifications, internal then external staff reinforcements, net capacity increase, search for alternative solutions to traditional equipment supplies routes, etc. have been a part of the solution. Despite the alerts from the ground, national action remained out of step with understanding of the seriousness of the local situation, with recommendations and actions either inapplicable or too late to implement. There was a strong feeling of isolation among health care organizations and professionals, reinforced by the absence of representatives from health institutions and particularly from the regional health agency in the field. Two main elements can be highlighted: a strong cohesion of the whole hospital center through teamwork and groundwork between the caregivers and the management, as well as the implication of all the actors of the emergency medicine (public staff, private staff, liberal staff, departmental fire, and rescue service);they were the determining factors in our capability to face this unprecedented event.

Sense of Place and Belonging: Lessons from the Pandemic

This study investigates how students experienced a sense of place and a sense of belonging in both in-person and virtual learning environments by analyzing student interview data. As educators and university students grapple with the ongoing COVID-19 pandemic, we consider how students experience the presence and absence of sense of place and belonging, and how this could inform faculty and staff practices. We conclude by offering recommendations for university educators, with a particular focus on the benefits of building communities of practice. © 2022 University of Calgary. All rights reserved.

A Correct Face Mask Usage Detection Framework by AIoT

The COVID-19 pandemic, which affected over 400 million people worldwide and caused nearly 6 million deaths, has become a nightmare. Along with vaccination, self-testing, and physical distancing, wearing a well-fitted mask can help protect people by reducing the chance of spreading the virus. Unfortunately, researchers indicate that most people do not wear masks correctly, with their nose, mouth, or chin uncovered. This issue makes masks a useless tool against the virus. Recent studies have attempted to use deep learning technology to recognize wrong mask usage behavior. However, current solutions either tackle the mask/non-mask classification problem or require heavy computational resources that are infeasible for a computational-limited system. We focus on constructing a deep learning model that achieves high-performance results with low processing time to fill the gap in recent research. As a result, we propose a framework to identify mask behaviors in real-time benchmarked on a low-cost, credit-card-sized embedded system, Raspberry Pi 4. By leveraging transfer learning, with only 4-6 h of the training session on approximately 5,000 images, we achieve a model with accuracy ranging from 98 to 99% accuracy with the minimum of 0.1 s needed to process an image frame. Our proposed framework enables organizations and schools to implement cost-effective correct face mask usage detection on constrained devices.

Forecasting container freight rates using the Prophet forecasting method

This study applies three innovative methods in forecasting container freight rates. Firstly, we extracted 471 major disruptive events from the ‘Lloyds List' database from 2010 until 2020, that may affect freight rates. Secondly, we use Machine Learning (ML) and natural language processing techniques to categorize these events into six distinct categories. These include: "congestion”, "peak demand”, "policy”, "price up”, "overcapacity”, and "coronavirus”. Thirdly, we apply Prophet forecasting on six major container routes by incorporating the six categories of events. The results reveal that ‘overcapacity' and ‘coronavirus' led to improved forecasting accuracy of freight rates when compared to the Prophet model without accounting for events. This study provides a more reliable mixed-method approach to improving the accuracy of container freight rate forecasts. The proposed forecasting technique will help policy makers and practitioners to develop and deploy strategies to mitigate the risks associated with the volatility of freight rates and supply chain costings. © 2023 The Authors

One-month Humoral Response Following Two Doses of Covid-19 Vaccines in Specific populations - ANRS0001S COV POPART Cohort Study

Background. We evaluated the immune response to COVID-19 vaccines in several specific populations at high risk of severe COVID-19. Methods. Participants from the French national multi-center prospective cohort studyANRS0001S COV-POPART were included (11 specific subpopulations: and 2 control groups (18-64 years and over 65 years)). In this preliminary analysis patients and controls who had received at least two vaccine doses have been included. Percentages (95% confidence intervals (CI)) of participants with anti-Spike SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies (in vitro neutralization assay) were evaluated at one month after the second dose of COVID-19 vaccine. Results. 3703 were included: 2650 participants from specific subpopulations (171 solid cancers, 160 SOT, 100 HCT, 91 chronic renal failures, 141 systemic autoimmune diseases, 157 autoimmune inflammatory rheumatic diseases, 361 multiple sclerosis (MS) or neuromyelitis optica spectrum disorders, 61 hypogammaglobulinemia, 401 diabetic, 739 obeses non-diabetic and 476 HIV) and 1053 controls (893: 18- 64 years and 160 over 65 years). Median age was 51.7 years [InterQuartile range: 40.8 - 60.9] and 50.7% were male. Most of the participants received BNT162b2 vaccine (86.4%). In the control group, 100% (95%CI: 99.6;100.0) of those aged 18-64 and 99.4% (96.6;100.0) of those over 65 years developed anti-Spike IgG antibodies. PLWHIV, cancer and diabetic patients had high rate of responders after two doses with 98.3% (97.2;99.1), 93.0% (88.1;96.3) and 92.0% (88.9;94.5), respectively. The lowest percentage of responders was found in patients with SOT (13.8% (8.8;20.1), HSCT (34.0% (24.8;44.2) and hypogammaglobulinemia (52.5% 39.3;65.4). In both control groups, the frequency of neutralizing antibodies was similar to the anti-Spike IgG antibody response. In the immunodeficient populations, neutralizing antibodies responders tended to be less frequent than anti-Spike antibodies responders. Similar trends than for IgG antibody were identified (Figure 1). Anti-Spike and Neutralizing antibody (Ab) responses (95% CI) one month after the second dose of COVID-19 vaccine in specific and control populations. Conclusion. Lower COVID-19 vaccine humoral response was observed in specific populations than in controls, especially in patients with hypogammaglobulinemia, HSCT and SOT. (Figure Presented).

Face Recognition Based on Deep Learning and Data Augmentation

Face recognition is one of the most popular applications in video surveillance systems and computer vision. The researches of face recognition in recent years have been shown that their applications are widely used in practice. Particularly, during the pandemic of Covid-19, there were a lot of researches relating to face recognition with and without mask. The accuracy of the face recognition algorithms is depended on technical issues, implemented solutions and models of data processing. In this paper, we propose an improved method for face recognition based on deep learning techniques and data augmentation. Our contribution of the proposed method is focused on the following steps: (1) obtaining and pre-processing data for training dataset based on image processing techniques (i.e. noise removal, mask wearing). (2) Creating a trained model of new dataset based on the Inception Resnet-v1. (3) Building an application for face recognition in timekeeping of a company. We use the two popular face datasets which are open source and publicity available: Casia-WebFace [1] for training and LFW [2] for validation. Comparing the several methods, the accuracy of our method is higher in case with mask and the processing time is very fast in the real time. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

A Correct Face Mask Usage Detection Framework by AIoT

The COVID-19 pandemic, which affected over 400 million people worldwide and caused nearly 6 million deaths, has become a nightmare. Along with vaccination, self-testing, and physical distancing, wearing a well-fitted mask can help protect people by reducing the chance of spreading the virus. Unfortunately, researchers indicate that most people do not wear masks correctly, with their nose, mouth, or chin uncovered. This issue makes masks a useless tool against the virus. Recent studies have attempted to use deep learning technology to recognize wrong mask usage behavior. However, current solutions either tackle the mask/non-mask classification problem or require heavy computational resources that are infeasible for a computational-limited system. We focus on constructing a deep learning model that achieves high-performance results with low processing time to fill the gap in recent research. As a result, we propose a framework to identify mask behaviors in real-time benchmarked on a low-cost, credit-card-sized embedded system, Raspberry Pi 4. By leveraging transfer learning, with only 4–6 h of the training session on approximately 5,000 images, we achieve a model with accuracy ranging from 98 to 99% accuracy with the minimum of 0.1 s needed to process an image frame. Our proposed framework enables organizations and schools to implement cost-effective correct face mask usage detection on constrained devices. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

EFFECT OF ACE AND COPING ON COVID SELF-EFFICACY

It is well established that exposure to Adverse Childhood Experiences (ACEs) can have a profound negative impact on physical and mental health and other health-related processes (e.g. decision making;Chang et al. 2019). Research has also indicated that individual differences in coping styles represent one pathway through which exposure to ACEs can confer risk for negative health outcomes (Sheffler et al. 2019). It is less clear however, whether the negative effects of exposure to ACEs extend also to one's self-efficacy for preventing and overcoming COVID-19. The current study aimed to examine the relationship between ACEs, measured as the total number of adverse childhood experiences endorsed on the Adverse Childhood Experiences Scale, and self-efficacy for preventing and overcoming COVID-19, measured using a modified version of the Self-Efficacy for Middle East Respiratory Syndrome. In addition, we examined whether the use of avoidant coping strategies (denial, venting, and behavioral disengagement) derived from a principal components analysis of the Brief Coping Questionnaire, statistically mediated the association between ACE scores and COVID-19 self-efficacy. Young adults (N = 86, Mage = 23.6;69% female;34% Asian, 33% white, 23% Latinx, 8% Mixed Race, 2% Black or African American) completed measures as part of a larger study. A series of linear regression analyses indicated that both exposure to a greater number of ACEs (β = -.23, p = .033) and greater use of avoidant coping strategies (β = -.36, p < .001) were associated with lower COVID-19 self-efficacy. On the other hand, ACE scores did not significantly predict the use of avoidant coping strategies (β = .09, p = .41) and when entered into a model simultaneously, both ACEs (β = -.20, p = .049) and coping (β = -.34, p = .001) remained significant predictors of COVID-19 self-efficacy. These results indicate that ACE scores and the use of avoidant coping strategies independently affect COVID-19 self-efficacy, and confirm that the negative health effects of ACEs extend also to perceptions of ability to prevent and overcome COVID-19.

The impact of the COVID-19 pandemic on the stressful relationship between parents and children

The stressful relationship between children and parents is the pain both go through when they find themselves unable to cope as a parent or a child. In order to find out the status, causes, and impacts of the COVID-19 pandemic and suggest some solutions to reduce stress between parents and children, we surveyed the impact of the COVID-19 pandemic on stressful relationships between parents and children at high school age in Da Nang city. The findings of a survey conducted on 550 randomly selected parents and 550 high school students using the Perceived Stress Scale reveal a high rate of tension between parents and their children, particularly up to 51.1% and 38.5%, respectively. In reality, many factors are affecting the stressful relationship between parents and their children at this age, in which psychological fear about health;social distancing policy;closed schools;students staying at home 24 hours a day and learning online;the disruption in children's daily routine;excessive use of electronic devices are major causes of stress in the relationship between parents and their children. From this practice, our research team has proposed such solutions as participating in creative activities and consulting the handbook instructing parents' behaviour rules toward children and vice versa, designing extra-curricular activities, and organizing training courses on life values for both parents and children to increase happiness and reduce stress in the parent-child relationship.

COVID-19 infection in the elderly in French-speaking Switzerland: an inventory of beliefs, convictions and certainties

Most patients hospitalized for COVID-19 are aged over 70 years old, and half of those who die are over 83 years old. Older patients do not always present with typical symptoms (fever, cough and dyspnoea) but sometimes are and remain asymptomatic (contact screening), or have aspecific presentations (altered general condition, falls, delirium, unusual fatigue). Rectal swab, which minimizes exposition risk, appears useful in long-term care patients with diarrhea. Older age is associated with worse prognosis, but the analysis should be refined by means of prognostic indexes that account for the heterogeneous health, functional, and cognitive status of the elderly population. Gathering elderly patients’ wishes and assessing their remaining life expectancy allows to anticipate care decisions according to the level of tension in the health system.

COVID-19-RELATED MYOCARDITIS RESULTING IN CARDIOGENIC SHOCK

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus-19 (COVID-19) myocarditis showed increased mortality despite team work of experts. We present a case of a middle-aged male with COVID-19 related myocarditis leading to cardiogenic shock. CASE PRESENTATION: 64-year-old male with history of hypertension, hyperlipidemia, hypothyroidism and positive COVID-19 infection with related stroke presented with 2 weeks of myalgias, malaise, and dyspnea. He was tachycardic on exam with bibasilar crackles and mild pedal edema. Labs revealed elevated inflammatory markers, cardiac biomarkers and leukocytosis with peripheral eosinophilia. Pulse dose steroids were initiated for suspected vasculitis. Transthoracic echocardiogram (TTE) revealed global hypokinesis and cardiac catheterization revealed LVEDP of 28 mmHg, LVEF of 10%, and cardiac index of 1.7 L/min/m2 without ischemic disease. Inotropes were started, and the patient was transferred to the center for advanced heart failure and cardiac transplant evaluation. Cardiac MRI (CMRI) revealed late enhancing subendocardial myocardial scarring of anteroseptal segments and endomyocardial biopsy revealed focal ischemic injury suggestive of COVID-19 related myocarditis in the setting of multisystem inflammatory syndrome (MIS-A). DISCUSSION: MIS-A is a rare subacute complication of COVID-19, thought to be caused by direct cell injury from ACE2 upregulation and a dysregulated immune response resulting in acute myocarditis. Elevated troponins have been reported in these patients due to ventricular dilation and direct myocardial injury. Electrocardiograms have poor sensitivity for myocarditis, thus TTE is performed which reveals wall abnormalities with reduced ventricular function and has been reported in 60% of COVID-19 related myocarditis cases. CMRI is preferred to evaluate myocarditis and may reveal hyperemia, edema, and myocardial necrosis. Endomyocardial biopsy (EMB) is the gold standard for diagnosing myocarditis, but should be a shared decision due to lack of studies to support EMB diagnosis in suspected COVID-19 myocarditis. Patients with cardiogenic shock need vasopressors and inotropes, and mechanical circulatory support via extracorporeal membrane oxygenation or intra-aortic balloon pumps if needed. It is unclear if intravenous immunoglobulins or steroids have benefit treating COVID-19-related myocarditis and requires further evaluation. CONCLUSIONS: Myocarditis should be suspected in patients with COVID-19 infection presenting with acute heart failure. Given limited data for COVID-19 related myocarditis, we need more studies to better treat these patients. REFERENCE #1: Morris SB, Schwartz NG, Patel P, et al. Case series of multisystem inflammatory syndrome in adults associated with sars-cov-2 infection — united kingdom and united states, march–august 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1450–1456. REFERENCE #2: Sawalha K, Abozenah M, Kadado AJ, et al. Systematic review of COVID-19 related myocarditis: insights on management and outcome. Cardiovasc Revasc Med. 2021;23,107-113. REFERENCE #3: Siripanthong B, Nazarian S, Muser D, et al. Recognizing covid-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management. Heart Rhythm. 2020;17(9):1463-1471. DISCLOSURES: No relevant relationships by Suong Nguyen, source=Web Response No relevant relationships by Nikola Perosevic, source=Web Response No relevant relationships by Evan Wasserman, source=Web Response

CAN OUTCOMES IN PATIENTS WITH COVID-19 PNEUMONIA AND ACUTE RESPIRATORY BE PREDICTED WITH ADMISSION SERUM LACTIC ACID LEVELS?

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Within the last year, Coronavirus-19 (COVID-19) has been observed to cause extensive multi-system complications including death and has become a challenge for health care providers. Lactic acid is a biomarker that accumulates when the body has increased anaerobic production or decreased clearance. It has been used to predict mortality in acute illnesses causing multiorgan failure secondary to hypoxia and hypoperfusion. In patients infected with COVID-19, a known complication is cytokine storm due to a dysregulated inflammatory response leading to refractory hypoxemia, lactic acidosis and acute respiratory distress syndrome (ARDS). The objective of this study was to determine if admission lactic acid levels correlated with outcomes including hospital length of stay (LOS), intensive care unit (ICU) LOS and mortality in patients with acute respiratory failure due to COVID-19 pneumonia. METHODS: One-hundred and five (105) patients, admitted for acute respiratory failure due to COVID-19, were retrospectively studied. Patient demographics including patient age, gender, ICU LOS, hospital LOS, admission serum lactic acid levels, and mortality were obtained through reviewing medical records. Statistical analysis to determine the correlation between admission lactic acid levels, hospital LOS, ICU LOS and mortality was performed using Pearson’s correlation with a p ≤0.05 being statistically significant. Independent t-test was used to determine impact of admission serum lactic acid levels on mortality. RESULTS: Of the 105 patients studied, 84 patients had an admission lactic acid level. Of these 84 patients, 70% were male, and the mean age was 65.65 ± 16.05 years. Pearson’s correlation analysis revealed significant correlation between admission lactic acid levels and mortality (r = -0.265;p = 0.01). The mean admission lactic acid level was 2.3 ± 2.2 mmol/L in non-survivors compared to 1.4 ±1.1 mmol/L in survivors (p = 0.01, independent t-test). However, there was no statistically significant correlation between admission lactic acid levels and hospital LOS (r= 0.03, p = 0.77) or ICU LOS (r=0.1, p = 0.34). CONCLUSIONS: The study demonstrated a significant correlation between admission lactic acid levels and mortality in patients with acute respiratory failure due to COVID-19 pneumonia, but not with lCU or hospital length of stay. The mean lactic acid levels on admission were also higher in non-survivors. CLINICAL IMPLICATIONS: Admission lactic acid levels might help in triaging and prognostication patients with acute respiratory failure due to COVID-19 pneumonia. Patients with higher lactic acid levels might be better managed in units with closer monitoring and intensive care. Further studies may also outline if there is a specific serum lactic acid level that correlates with the increased mortality risk in patients with acute respiratory failure due to COVID-19. DISCLOSURES: No relevant relationships by Debapriya Datta, source=Web Response No relevant relationships by Manasvi Gupta, source=Web Response No relevant relationships by Gaurav Manek, source=Web Response No relevant relationships by Suong Nguyen, source=Web Response

IMPACT OF ADMISSION TROPONIN AND TROPONIN RISE DURING HOSPITALIZATION ON MORTALITY IN COVID-19 PNEUMONIA WITH ACUTE RESPIRATORY FAILURE

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: COVID-19 can cause multi-organ failure and death. Troponin levels may be elevated in such patients from demand ischemia due to hypoxia versus direct myocardial injury. The information regarding association between troponin levels and mortality is limited in COVID 19 patients. In our study, we specifically determined the correlation of admission troponin as well as troponin rise during hospitalization in COVID-19 patients with acute respiratory failure with mortality. METHODS: Medical records of seventy one (71) patients with COVID-19 pneumonia and acute respiratory failure were reviewed to determine demographic features, admission troponin, rise in troponin (peak troponin - admission troponin) and survival. Pearson’s correlation analysis was performed to evaluate the correlation between admission troponin, rise in troponin and mortality. Independent t-test was used to determine the impact of admission troponin on hospital mortality. P < 0.05 was deemed statistically significant. RESULTS: Seventy-three percent (73%) of studied patients were male. Average age was 47.7 ± 16.7 years. Twenty-two percent (22%) of patients expired. Mean admission troponin was: 0.18 ± 1.1 ng/mL. Mean troponin rise (peak troponin - admission troponin) during hospital stay was: 0.7 ± 3.18 ng/mL. Admission troponin in survivors was 0.03 ± 0.04 ng/mL and in non-survivors was: 0.9 ±2.6 ng/mL (p = 0.02, independent t-test). Troponin rise in survivors was 0.7 ± 3.5 ng/mL and in non-survivors was: 0.55 ± 1.6 ng/mL (p=0.8, independent t-test). Pearson’s correlation analysis showed significant correlation between admission troponin and mortality (r = -0.292, p= 0.028) but no correlation between troponin rise and mortality (r = 0.02;p= 0.83). CONCLUSIONS: A higher troponin at admission has a significant correlation with mortality in COVID19 patients with acute respiratory failure. However, there was no significant correlation between rise in troponin levels and mortality which may have been due to a small sample size in our study. CLINICAL IMPLICATIONS: Troponin levels on admission can be utilized to predict outcomes in patients with COVID-19 pneumonia and acute respiratory failure. Further studies need to be done to determine whether a rise in troponin levels can also be predictor of mortality. Future studies can also determine if increased mortality is seen at specific troponin levels in patients with COVID 19 pneumonia DISCLOSURES: No relevant relationships by Debapriya Datta, source=Web Response No relevant relationships by Manasvi Gupta, source=Web Response No relevant relationships by Gaurav Manek, source=Web Response No relevant relationships by Suong Nguyen, source=Web Response

Predicting the length of stay in hospital emergency rooms in rhode island

Predicting a patient’s length of stay (LOS) in a hospital setting has been widely researched. Accurately predicting an individual’s LOS can have a significant impact on a healthcare provider’s ability to care for individuals by allowing them to properly prepare and manage resources. A hospital’s productivity requires a delicate balance of maintaining enough staffing and resources without being overly equipped or wasteful. This has become even more important in light of the current COVID-19 pandemic, during which emergency departments around the globe have been inundated with patients and are struggling to manage their resources. In this study, the authors focus on the prediction of LOS at the time of admission in emergency departments at Rhode Island hospitals through discharge data obtained from the Rhode Island Department of Health over the time period of 2012 and 2013. This work also explores the distribution of discharge dispositions in an effort to better characterize the resources patients require upon leaving the emergency department. © 2021 by Emerald Publishing Limited.

LARGE SCALE MANUFACTURING AND POTENCY ASSAY DEVELOPMENT FOR HMSCS IN REGENERATIVE MEDICINE

Background & Aim: A consortium of leading human mesenchymal stem/stromal cell (hMSC) therapy developers, Sentien Biotechnologies, GenCure Biomanufacturing and RoosterBio, are developing a large-scale hMSC biomanufacturing process with a deep Quality focus, culminating in a potency assay qualified with human clinical samples. Methods, Results & Conclusion: A Xeno-Free (XF), fed-batch, microcarrier-based bioreactor process for hMSC manufacturing had been developed and optimized [1], and scaled to a 50L process, with demonstrated comparability between the hMSC critical quality attributes (CQAs) from the bioreactor process and from 2D control cells of similar population doubling (PDL) [2]. Based on this previous process development, GenCure and RoosterBio are leading the first stage of biomanufacturing through upstream (2D seed train & bioreactor expansion) and downstream process (continuous counterflow centrigufation, formulation & fill, and cryopreservation). Bioreactor runs at the 50 L scale were performed using the most commonly used hMSC sources in regenerative medicine: bone marrow (BM-MSCs), umbilical cord (UC-MSCs) and adipose (AD-MSCs). Critical process parameters (CPPs) are defined and critical quality attributes (CQAs) of the harvested cell product are characterized. An initial production run produced over 33billion BM-MSCs that passed the ISCT minimal criteria for MSCs. The subsequent expansion of UC- and AD-MSCs will be presented. Sentien's proprietary platform was used to ask questions on how the MSCs reacted to different stimuli with results showing that BM-MSCs were able to sense and respond with different secretomes to inflammatory stimuli. Our data also showed that BMMSCs induced changes in CD4, CD8 and CD19 cells and significantly reduced TNF-a levels in activated PBMCs, demonstrating their immunomodulatory capabilities. The same assays will be performed using the resulting MSCs from umbilical cord and adipose tissue expanded in the 50L bioreactor. Sentien, which has treated 16 subjects with acute kidney injury (AKI, open IND) and is currently running a trial in severe COVID-19 patients with AKI, will contribute biomarker data from the clinical-scale bioreactor and patient samples. Testing the in vitro developed potency hypothesis against the clinical samples will form the basis of a true potency assay. Through this work, the consortium will develop a generalized quality framework for large scale MSC manufacturing and potency assay development for broad use in regenerative medicine.

Séroprévalence SARS-Cov-2 chez les professionnels de santé : étude multicentrique avec analyse des facteurs de risque professionnels et extraprofessionnels

Introduction L’objectif de notre étude était d’évaluer la séroprévalence SARS-Cov-2 chez les professionnels de santé, après la première vague Covid-19, et d’analyser les facteurs professionnels et extraprofessionnels modifiant cette prévalence. Matériels et méthodes Suite aux instructions gouvernementales proposant de réaliser une sérologie Covid-19 à tout professionnel de santé après la première vague, nous avons réalisé une étude transversale, multicentrique. Tous les professionnels volontaires des quatre centres participants étaient invités à réaliser une sérologie et à remplir un questionnaire concernant leurs données démographiques, leurs caractéristiques professionnelles, l’utilisation des équipements de protection individuelle et l’exposition extra professionnelle au Covid-19. Nous avons calculé la prévalence SARS-Cov-2 et utilisé une régression logistique en appliquant un effet centre. Résultats Un total de 3454 professionnels ont participé à l’étude dont 83,4 % de femmes. L’âge moyen était de 40,6 ans [31,8–50,3]. En médiane, la prévalence sérologique SARS-Cov-2 était de 5 % (95 % IC, 4,3 %–5,8 %). Les facteurs associés à une plus forte séroprévalence étaient : l’âge<30 ans (aOR=1,59, (95 % IC, 1,06–2,37)), le statut d’étudiant (aOR=3,38, (95 % IC, 1,62–7,05)) avec une séroprévalence de 16,9 % dans cette catégorie. L’unité de travail, y compris le fait d’avoir travaillé en unité Covid ou en réanimation, ainsi que l’exposition à des patients (quel que soit leur statut infectieux) n’étaient pas associé à une augmentation de la séroprévalence. Par contre les professionnels rapportant un contact avec un patient Covid, sans protection adaptée, ou ayant pratiqué des taches aérosolisantes, y compris avec un masque FFP2, avaient un surrisque d’infection Covid-19 (respectivement aOR à 1,66 et 1,7). Enfin, l’exposition à un collègue infecté ou à un cas familial était également associée à une augmentation de la prévalence sérologique. Conclusion Les mesures mises en place pour limiter la transmission du SARS-Cov-2 des patients aux professionnels de santé semblent efficaces. En complément de la vaccination, l’éviction systématique des professionnels infectés, la formation des étudiants et le rappel des mesures d’hygiène durant les temps de pause pourraient limiter la contamination des professionnels de santé.