Economic policy and economic research in Brazil during the pandemic

How did the COVID-19 crisis impact the field of economic policy and research in Brazil? In a country where inequality is among the highest in the world and the economic situation of the poor was steadily worsening, one could expect a radical shift towards welfare policies to protect income and jobs. Yet economic debate is far from reaching a consensus on the need for fiscal measures;it remains highly polarised among politicians and opinion makers. This chapter analyses economic policy and research in Brazil before and during the pandemic, focusing on the debate between economic austerity and welfare policies. It argues that COVID-19 has brought to the surface many concerns that were already haunting economic debate, such as the current fiscal rule (spending ceiling rule) revision and the increase in public debt. At the same time, it consolidated the fields of economic development and social economics as being among the priorities of Brazilian scholars. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Educaci?n en contextos rurales en tiempos de pandemia. Relatos Brasil-Argentina

Santiago (USACH), Resumen. Este articulo tiene como objetivo describir y visibilizar las intervenciones realizadas por docentes para dar continuidad a las clases de aulas rurales durante la pandemia de la covid-19 en dos regiones de America Latina. Durante los meses de mayo y junio del ano 2020 se aplico un estudio de casos multiples en el estado de Minas Gerais (Brasil) y la provincia de Misiones (Argentina). Se entrevistaron 20 docentes y se utilizo el analisis de contenido categorico para procesar los relatos. Los hallazgos permitieron conocer tanto las dificultades presentes en las aulas rurales como la ineficacia y falta de especificidad territorial de las politicas educativas implementadas durante la pandemia. Por ultimo, los relatos de las y los docentes sirven de archivo historico al cual se puede volver y utilizar como guia para futuras intervenciones. Palabras clave: educacion rural;pandemia;Brasil;Argentina. Educacao em contextos rurais em tempos de pandemia. Relatos Brasil-Argentina Resumo. Este artigo tem como objetivo descrever e trazer a tona as intervencoes realizadas por pro-fessores para dar continuidade as aulas em salas de aula rurais durante a pandemia de COVID-19 em duas regioes da America Latina. Durante os meses de maio e junho de 2020, foi aplicado um estudo de caso multiplo no estado de Minas Gerais (Brasil) e na provincia de Misiones (Argentina). Vinte professores foram entrevistados e a analise de conteudo categorial foi usada para processar os relatos. As descobertas permitiram conhecer tanto as dificuldades presentes nas salas de aula rurais quanto a ineficacia e falta de especificidade territorial das politicas educacionais implementadas durante a pandemia. Por ultimo, os relatos dos professores servem como um arquivo historico que pode ser retomado e utilizado como guia para futuras intervencoes. Palavras-chave: educacion rural;pandemia;Brasil;Argentina. Rural education in pandemic times. Brazil-Argentina reports . This article aims to describe and make visible the interventions carried out by teachers to provide continuity to rural classrooms during the covid-19 pandemic in two regions of Latin America. During May and June 2020, we applied a multiple case study design in Minas Gerais (Brazil) and Mi-siones (Argentina). We interviewed twenty teachers and used categorical content analysis to process the reports. The findings revealed the difficulties in rural classrooms and the ineffectiveness of the territorial specificity of the educational policies implemented during the pandemic. Finally, the teachers' reports serve as a historical archive to which we can return and use as a guide for future interventions.

Scenarios of social isolation during the first wave of the COVID-19 pandemic in Rio de Janeiro, Brazil

This work analyses the construction of social isolation as a public problem during the first wave of COVID-19, drawing on experiences in Rio de Janeiro which, in addition to being one of the country's major cities, had among the highest mortality rates in Brazil in 2020. We consider both the legal measures enacted by government agencies to contain the contagion and media coverage on the effects of these measures at the local level. The results show that, in the absence of compulsory confinement measures, urban public spaces were deployed both by government agencies and the media in a process by which social isolation was framed as a public problem. Legal measures affected daily patterns of movement, mobility, and sociability, and intervened in the dynamics of central urban functions and in access to and use of public spaces. Media reports gave voice to levels of public agreement or disagreement with regulations and emphasised the significance of legal measures to contain the spread of the virus. Public spaces are at the core of debates about compliance with legal measures to enforce social isolation because they are privileged places where social issues become visible and problematic material expressions of relationships between citizens and the law.

Regional and sectorial impacts of the COVID-19 pandemic in Sergipe, Brazil

This paper aims at estimating the regional and sectoral impacts of the Covid-19 pandemic in the state of Sergipe, Brazil in 2020. We use an input-output model with partial hypothetical extraction. The main results suggest a significant reduction in economic activity in the state, particularly in the Transport and Industry sectors. On the other hand, the Real estate and Food and Accommodation sectors have a greater capacity for recovery with the introduction of an emergency aid program. The municipalities with the largest absolute impact on gross domestic product are Aracaju, Canindé de São Francisco and Nossa Senhora do Socorro, two of them located in the metropolitan area of Aracaju. © 2023 Wiley Periodicals LLC.

Last year challenge of Nuclear Medicine: medical radioisotopes supply

Aim/Introduction: 99mTc is used in about 80% of the convencional diagnostic nuclear imaging procedures and represent yearly approximately 30 million examinations/year worldwide a year in diagnostic tests in hospitals, among others by oncology, cardiology and neurology.The production of radiopharmaceuticals for use in Nuclear Medicine has a complex system. It involves carefully calculated production schedules that take into account supply, demand and many logistical operations.The aim of this study is to show how our nuclear medicine department manage the impact of the shortly 99Mo supply chain and consequently, in the 99mTc availability and other radiopharmaceuticals produced in nuclear reactora. Material(s) and Method(s): European nuclear medicine organizations had just pay attention to how the COVID-19 pandemic might affect different parts of the 99Mo supply chain when had to dealt again faced with a new problem;the shortness 99Mo production. There are only five nuclear reactors involved in the production of 99Mo on industrial scale. These aging reactors are subject to unscheduled shutdowns and longer maintenance periods making the 99Mo supply chain vulnerable. In the last few months at our nuclear medicine department we had to reinvent ourselves so as not to completely stop carrying out the previously scheduled exams and therapies. Result(s): The use of technetium generators in Europe represents about 17% - 25% of the worldwide consumption of 99Mo, representing 30,000 exams per day and about 1.1 million doses per month. The main consequences at the IPO-Porto was;Delays in diagnosis/staging, rescheduling exams, change of surgery dates (Sentinel Ganglion and Myocardial Perfusion Cardiacs), weeks of overbooking, delay in follow-up of Glomerular Filtration Rate in pre- or post-transplant patients, postponement of 131I Therapies, Scintigraphy and Whole Body Scintigraphy in patients who were already in hypothyroidism. we had to reinvent the use of 99mTc generators, change exams appointments times, reagroup exams types by defined days and other radiopharmaceutical management tools that were not commonly used. Conclusion(s): Approximately 2/3 of scheduled exams were postponed and we had to deal with weekly and daily stock updates. Our department suggest some measures and procedures that could help with future 99Mo shortages, in order to be ready in future situations and to avoid shortness of production: the creation of a centralized European radiopharmacy system, European policies to encourage long-term investment, homogenization of marketing specifications in the Member States, solid databases of radiopharmaceuticals used/ available in Europe and encouraging cooperation between other countries outside the European Union.

Last year challenge of Nuclear Medicine: medical radioisotopes supply

Aim/Introduction: 99mTc is used in about 80% of the convencional diagnostic nuclear imaging procedures and represent yearly approximately 30 million examinations/year worldwide a year in diagnostic tests in hospitals, among others by oncology, cardiology and neurology.The production of radiopharmaceuticals for use in Nuclear Medicine has a complex system. It involves carefully calculated production schedules that take into account supply, demand and many logistical operations.The aim of this study is to show how our nuclear medicine department manage the impact of the shortly 99Mo supply chain and consequently, in the 99mTc availability and other radiopharmaceuticals produced in nuclear reactora. Material(s) and Method(s): European nuclear medicine organizations had just pay attention to how the COVID-19 pandemic might affect different parts of the 99Mo supply chain when had to dealt again faced with a new problem;the shortness 99Mo production. There are only five nuclear reactors involved in the production of 99Mo on industrial scale. These aging reactors are subject to unscheduled shutdowns and longer maintenance periods making the 99Mo supply chain vulnerable. In the last few months at our nuclear medicine department we had to reinvent ourselves so as not to completely stop carrying out the previously scheduled exams and therapies. Result(s): The use of technetium generators in Europe represents about 17% - 25% of the worldwide consumption of 99Mo, representing 30,000 exams per day and about 1.1 million doses per month. The main consequences at the IPO-Porto was;Delays in diagnosis/staging, rescheduling exams, change of surgery dates (Sentinel Ganglion and Myocardial Perfusion Cardiacs), weeks of overbooking, delay in follow-up of Glomerular Filtration Rate in pre- or post-transplant patients, postponement of 131I Therapies, Scintigraphy and Whole Body Scintigraphy in patients who were already in hypothyroidism. we had to reinvent the use of 99mTc generators, change exams appointments times, reagroup exams types by defined days and other radiopharmaceutical management tools that were not commonly used. Conclusion(s): Approximately 2/3 of scheduled exams were postponed and we had to deal with weekly and daily stock updates. Our department suggest some measures and procedures that could help with future 99Mo shortages, in order to be ready in future situations and to avoid shortness of production: the creation of a centralized European radiopharmacy system, European policies to encourage long-term investment, homogenization of marketing specifications in the Member States, solid databases of radiopharmaceuticals used/ available in Europe and encouraging cooperation between other countries outside the European Union.

Clinical Outcomes of Outpatients With Suspected Covid-19 Treated With Chloroquine Compounds in Brazil: A Nationwide Telemedicine Study

Introduction: Following the inception of the COVID-19 pandemic, chloroquine compounds were proposed as potential therapeutic strategies, at the cost of a potential increase in cardiovascular risk. We aimed to evaluate clinical outcomes of patients with COVID-19, comparing those using chloroquine compounds to individuals without specific treatment. Method(s): Outpatients with suspected COVID-19 in Brazil who had at least 1 ECG transmitted to a Telehealth Network, were prospectively enrolled in 2 arms (G1: treatment with chloroquine compounds and G2: without specific treatment) and G3: registry of other specific treatments. Outcomes were assessed through follow-up phone calls on days 3 and 14, and also administratively collected from national mortality and hospitalization databases. The primary outcome was composed of: hospitalization and all-cause death. The association between treatment groups and the primary outcome was evaluated by logistic regression. Significant variables (p<0.10) were included in 4 multivariate models: 1: unadjusted;2: adjusted for age and sex;3: adjusted for model 2 plus cardiovascular risk factors and 4: adjusted for model 3 plus COVID-19 symptoms (when available from phone contact). Result(s): In 303 days, 712 (10.2%) patients were allocated in G1 (chloroquine), 3623 (52.1%) in G2 (control) and 2622 (37.7%) in G3 (other treatments). Median age was 49 (IQR 38 - 62) years, 57% women. Of these, 1969 had successful phone contacts (G1: 260;G2: 871;G3: 838). The primary outcome was more frequent in groups 1 and 3 compared to the control group, when assessed exclusively by phone (G1: 38,5% vs. G2: 18,0% vs. G3: 34,2%, p<0,001) or combined with administrative data (G1: 19,5% vs. G2: 11,0% vs. G3: 18,2%, p<0,001). In the adjusted models, chloroquine independently associated with a greater chance of the primary outcome: phone contact (model 4): OR=3.24 (95% CI 2.31 - 4.54), p<0.001;phone + administrative data (model 3): OR=1.99 (95% CI 1.61 - 2.44), p<0.001. Chloroquine also independently associated with higher mortality, as assessed by phone + administrative data (model 3): OR=1.67 (95% CI 1.20 - 2.28). Conclusion(s): Chloroquine compounds associated with a higher risk of poor outcomes in outpatients with COVID-19 compared to standard care.

Experience report on an extension project with rural university students in times of a pandemic: training for research

In view of the pandemic scenario, caused by the new coronavirus (SARS-CoV-2), the Degree in Rural Education at the Federal University of Minas Gerais promoted, through the extension project "Povos do Campo and the COVID-19 Pandemic", actions aimed at bringing the University closer to the reality of the peasant population. Among the activities promoted, the mini -course "ABNT Standards for Academic Works and Academic Research Tools" was offered, whose main objectives, meeting the needs of students, help graduates, especially those in the process of writing the monograph, to master techniques of academic research, writing, formatting and standardization, as well as making them aware of the importance of academic research for society. The results of the mini-course showed that, even in pandemic times and in the midst of great difficulties in accessing resources, it was possible to promote strategies aimed at the inclusion of peasant peoples and overcoming social inequalities.

Do income policy mitigate the economic impacts of Covid-19 on tourism in Brazil?

This paper aims to estimate the hole of the government compensatory policy in order to mitigate the economic impact of pandemic COVID-19 on the tourism sector in Brazil. Tourist activities were the first to be strongly affected by the pandemic, and these impacts are expected to be the most prolonged ones. In this research, the method of partial hypothetical extraction, underling the input-output modeling, was used to simulate the economic impacts of two scenarios affecting the tourist activities and workers in this sector. As far as to our knowledge, this type of approach has never been applied before in the tourism context. The results show a potential decline of 31% in Gross Domestic Product (GDP) of tourist activities derived from the withdrawal of informal workers and tourist demand contraction. In addition, the government compensatory policy could mitigate these negative effects reducing it to 17%. Lodging services would be the most affected tourist activity.

Higher Angiotensin Converting Enzymes Activities Are Observed In Covid-19 Positive Volunteers

The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, Angiotensin Converting Enzyme 2 (ACE2). The depletion of the biological functions of ACE2, due to the internalization of the receptor along with SARS-CoV-2, leads to impairment of Renin Angiotensin System (RAS), which can contribute to COVID-19 pathogenesis. In addition, genetic differences in RAS may be associated with more severe symptoms and complications observed in COVID-19 patients. This study aims to perform a comparative analysis between COVID-19 positive patients and uninfected individuals, to correlate such disease profiles with ACE I/D (Insertion/Deletion) and ACE2 G8790A polymorphisms, and their enzymatic activities. The anthropometric, demographic, clinical and cardiovascular parameters of 764 individuals from Ipaussu/SP (Brazil) were evaluated. ACE and ACE2 activities were measured by fluorometric assays, and assessment of both enzymes polymorphisms was performed by PCR. In this cohort, 35,2% (269 of 764) the volunteers were positive for COVID-19. The prevalence of COVID-19 was higher among women (67%) and individuals aged between 18 and 49 years. Also, comorbidities as obesity and arterial hypertension were more frequent in the positive group, when considered individuals under 60 years old. Higher ACE and ACE2 enzymatic activities were observed in positive group (46.4 vs 41.6 and 11.3 vs 8.5, respectively). Individuals with ID genotype in the positive group presented higher ACE activity compared to individuals with same genotype in control group (46.9 vs 41.7). In the positive group, ACE activity was increased in the DD (54.5) when compared to ID (46.9) and II (37.9) genotypes. No significant differences related to ACE2 activity and polymorphism were observed. ACE/ACE2 activity ratio was higher in the COVID-19 negative group (4.7 vs 3.7). The increased ACE activity for the DD genotype was in line with the literature data for hypertension and cardiovascular diseases. We can suggest a synergic effect between ACE DD genotype and COVID-19 infection enhancing ACE activity, what may contribute to pro-inflammatory phenotype and more severe symptoms of COVID-19.

RECURRENCE OF CEREBRAL VENOUS THROMBOSIS IN PATIENTS IMMUNIZED AGAINST SARS-COV-2: A COHORT STUDY

Background and aims: Cerebral venous thrombosis (CVT) is a rare neurological condition. Several cases of CVT have been described in patients with SARS-CoV-2 infection and following vaccination against COVID-19 with ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines through vaccineinduced thrombotic thrombocytopenia (VITT). This study aims to analyze the CVT recurrence rate in patients immunized against SARS-CoV-2. Methods: Ambispective cohort study. Patients aged > 18 years and diagnosed with CVT between 2000-2021 were included and prospectively evaluated for vaccine-related events. Results: A total of 67 patients were included, 18 of which are still under etiological investigation (26.9%). Mean age was 43.5 ± 13.5 years and 47 patients were female (70.1%). Use of oral contraceptives was the most frequent cause in the sample (35.8%). Two patients in the sample had CVT from vaccine-induced thrombotic thrombocytopenia (VITT) with ChAdOx1 nCoV-19 vaccines (3.0%) and one had CVT from SARS-CoV-2 infection (1.5%). After the index CVT event, 33 patients have been immunized against SARS-CoV-2 with two doses (49.3%), 7 patients have been immunized with one dose (10.4%), 6 patients have not yet been immunized (9.0%). Of the 40 patients immunized after the index event, 28 (70%) were using oral anticoagulants and the remaining 12 patients had already completed one year of anticoagulation. There was no recurrence of CVT after immunization. Conclusions: Despite being related to a higher occurrence of CVT through VITT, vaccines against SARS-CoV-2 do not appear to increase the risk of CVT recurrence in this population.

Social vulnerability increased the non-motor worsening in people living with Parkinson's disease during the COVID-19 pandemic

Objective: To investigate the social vulnerability impact on motor and non-motor worsening in people living with PD during the COVID- 19 pandemic. Background: The COVID-19 pandemic has imposed a large variety of unparalleled challenges, many of which appear to be disproportionately impacting the mental and physical health of people living in different social vulnerability condition. People living with Parkinson's disease (PD) experimented a clinical worsening during the pandemic explained by multidimensional factors (Silva-Batista et al.,2021). Methods: One hundred people with a confirmed diagnosis of Idiopathic PD, 45 females, mean age of 67.3 years (SD = 9.2), in stage 1-3 of disease evolution according to Hoehn and Yahr classification, participated in the present study. After presenting the informed consent form, and expressing agreement to participate in the study, participants were asked to answer, through telephone interviews, a previously established questionnaire that investigates: (1) general information;(2) socioeconomic status;(3) information associated with PD;(4) quality of life worsening;(5) health conditions related to COVID-19;(6) mental health worsening;(7) fear of falling;(8) level of physical activity;(9) cognitive health conditions and (10) motor and non-motor aspects of daily life experience. The participants were divided into two groups, according to the social vulnerability condition: high social vulnerability group (HSV) and low social vulnerability group (LSG). The comparison in worsening severity of all factors between the two groups was analyzed by ANOVA one-way. Results: The groups were comparable in demographic and clinical aspects. The ANOVA showed a significant statistical difference between the groups only for pain (F(1,95) = 6.98, p = .009), urinary problems (F (1,96) = 4.47 p = .03), and apathy F(1,95) = 4.52, p = .03). The Tukey post-hoc confirmed a more severe worsening for HSV (p < .001). Conclusion: People with PD living in a high social vulnerability condition demonstrated increased non-motor worsening during the COVID-19 pandemic. These results emphasize the importance of developing support social and health assistance to alleviate the social vulnerability impact during the COVID-19 pandemic and other similar unexpected stress situations on people living with PD.

Gender differences in stress and mental health due to COVID-19 pandemic in people living with Parkinson's disease

Objective: To investigate the gender differences in the motor and non-motor worsening associated with COVID-19 pandemic in people living with PD. Background: The COVID-19 pandemic has imposed a large variety of unparalleled challenges, many of which appear to be disproportionately impacting the mental health and well-being of men and women. People living with Parkinson's disease (PD) experimented a clinical worsening during the pandemic explained by multidimensional factors, however, gender was not one of them. Investigate the gender influence on the response to adverse effects of stressful effects of unexpected conditions may help to guide preventive programs for people living with PD. Methods: 100 people with Idiopathic PD, 45 females, mean age of 67.3 years (SD = 9.2), in stage 1-3 of disease evolution according to H&Y classification, participated in the present study. After expressing agreement to participate in the study, participants were asked to answer, through telephone interviews, a previously established questionnaire that investigates: (1) general information;(2) socio-economic status;(3) information associated with PD;(4) quality of life worsening;(5) health conditions related to COVID-19;(6) mental health worsening;(7) fear of falling;(8) level of physical activity;(9) cognitive health conditions and (10) motor and non-motor aspects of DLA. The participants were divided into two groups, according to gender. The comparison in worsening severity of all factors between the two groups (male and female), was analyzed by ANOVA one-way. Results: The groups were comparable in demographic and clinical aspects. The ANOVA showed a significant statistical difference between the groups only for discouragement, sadness, hopelessness (F(1, 95) = 5.6, p = .01) and adaptation difficulty (F(1, 95) = 11.4, p = .001. The Tukey post-hoc confirmed a more severe worsening of mental health in females (p < .001). Conclusion: Females living with PD demonstrated higher levels of discouragement, sadness, hopelessness, and higher difficulty to adapt the social isolation during the COVID-19 pandemic. These results emphasize the importance of developing support assistance to mitigate the extensive negative impacts of the COVID-19 pandemic and other similar unexpected stress situations on people living with PD, as also of the development of specific interventions to the gendered impacts on mental health and well-being.

'No risk in the rural': information on COVID-19 among rural university

This article analyzed the reception, evaluation and circulation of information on COVID-19 between people living in rural communities located in municipalities in the interior region of the state of Minas Gerais, Brazil. This research is part of an extension project created in April 2020 with 128 students from a training course aimed at teachers for rural schools, offered by a Brazilian federal public university. Questionnaires with closed and open questions were applied in three stages: 35 students in the first stage (April/May 2020), 46 students in the second stage (July 2020) and 29 students in the third stage (June/July 2021). Data were analyzed using categorical content analysis. The results were organized into the following categories: a) means of communication to access information, b) focus of information, c) immunization through vaccine and d) false or misleading information. There is an excess of false information that could have aggravated the effects of the pandemic among rural and peasant populations in the analyzed context. Thus, given the insecurities of the pandemic scenario and the way in which the pandemic affects and is perceived by rural populations, there is still a need to create qualified spaces for access to scientific information as well as health guidelines for these people.

Chatbot as a Telehealth Intervention Strategy in the COVID-19 Pandemic: Lessons Learned from an Action Research Approach

The COVID-19 pandemic and the need for social distancing have created a demand for new and innovative solutions in healthcare systems worldwide. One of the strategies that have been implemented are chatbots, which can be helpful in providing reliable health information and preventing people from seeking assistance in healthcare centers and being unnecessarily exposed to the virus. In this context, although a high number of chatbots have been implemented worldwide, little has been discussed about the process and challenges in developing and implementing this technology. This paper reports on an action research, which designed a novel chatbot as a prompt response to the COVID-19 pandemic. The chatbot is intended to be a first layer of interaction with the public, performing triage of patients and providing information about COVID-19 on a large scale and without human contact. Our contribution is twofold: (i) we reflected on the development process and discussed lessons learned and recommendations to support a multidisciplinary development and evolution process of the chatbot;and (ii) we identified some interactive and technological features that can be used as a reference framework for this kind of technology. These contributions can be useful to other researchers and multidisciplinary teams facing similar challenges. © 2021 Latin American Center for Informatics Studies. All Rights Reserved.

Circulating Levels of Ang/Tie2 and VEGF-a Pathway Mediators Are Associated with Clinical Severity, Endothelial Barrier Disruption and Coagulation Activation in COVID-19

Background: the pathogenesis of severe COVID-19 involves the deregulated activation of different compartments of immunothrombosis, which are otherwise important for pathogen eradication and tissue repair. Coagulation activation, angiogenesis and alterations of endothelial barrier (EB) are elements of immunothrombosis that have been shown to be involved in the pathogenesis of COVID-19. Angiopoietins (Ang) 1 and 2 and their receptor Tie2 and VEGF-A are well-known pro-angiogenic mediators that, during inflammation also mediate EB disruption. Recently, it has also been demonstrated that the Ang/Tie2 pathway is involved in coagulation activation. Here we explored whether increased levels of angiogenesis/EB regulators (which have been previously associated with disease severity in COVID-19) are also associated with both EB disruption and coagulation activation in this condition. Methods: the study population consisted of 30 patients with COVID-19 confirmed by RT-PCR and presenting typical CT findings admitted due to hypoxemia. Thirty sex- and age-matched healthy individuals were recruited at the same time, from the same geographic region. Patients were part of a clinical trial (REBEC: U1111-1250-1843) but samples were obtained before any study intervention, within 24 hours from diagnosis confirmation. Circulating levels of angiogenesis/EB regulation mediators and coagulation biomarkers were measured by commercial assays (immunological or functional). Monolayers of endothelial cells from umbilical veins (HUVECs) or lung (HULECs) were used for measurement of EB integrity using an impedance sensor system (ECIS, Electric Cell-substrate Impedance Sensing System). Cells were stimulated with serum from patients or healthy individuals and EB integrity was continuously monitored for 36 hours. Clinical outcomes were obtained from the digital medical records. Results: mean length of hospital stay (LOS) was 12.9 ± 9.8 days. Twelve patients (40%) required intensive care (ICU) and 28/30 patients survived. Mean D-dimer was 3,609 ± 14,440 ng/mL. Circulating levels of Ang1, Ang2, sTie2 and VEGF-A were all significantly increased in patients compared to healthy individuals (Ang1: 463.2 ± 194.6 vs 237.4 ± 104.9 pg/mL, p<0.0001;Ang2: 1,926 (1,275 - 3,134) vs 1,215 (9 - 1,440 pg/mL), p<0.0001;Tie2: 10,753 ± 2,377 vs 8,603 ± 1,851 pg/mL, p<0.0001 and VEGF-A: 94.7 (73.4 - 116.0) vs 45.9 (39.7 - 57.0 pg/mL), p<0.0001.). In contrast, soluble VE-cadherin levels were decreased in patients compared to healthy individuals (1,234 ± 318 vs 1,539 ± 363 ng/mL, P=0.001). Serum from COVID-19 patients induced decreases of EB integrity in monolayers of both HUVECs and HULECs as early as 15 minutes, lasting up to 5 hours after stimulation (figure 1). The magnitude of EB disruption was correlated with clinically relevant outcomes such as time of ICU stay and LOS (figure 1). Interestingly, levels of Ang1, Ang2 and soluble VE-cadherin levels were also significantly correlated with the magnitude of EB disruption, as well as with biomarkers of coagulation activation such as fibrinogen, Von Willebrand Factor antigen levels, PAI-1, P-selectin and urokinase receptor (uPAR). Conclusions: Ang-1/Ang-2 mediated Tie2 signaling has been shown to be important for the fine regulation of barrier integrity and coagulation activation at the endothelial level, which are two critical elements of immunothrombosis. Our results provide evidence supporting that the interplay between these processes can play a role in the mechanisms driving COVID-19 severity, and suggest that targeting the Ang/Tie2 and VEGF-A pathways could be attractive strategies to modulate not only changes of the alveolar-capillary barrier, but also of coagulation activation in COVID-19. Figure 1. In (a), endothelial barrier (EB) integrity of HUVEC monolayers upon stimulation by serum from COVID-19 patients and healthy individuals (n=27-30 per group). The lower the normalized resistance, the higher the magnitude of EB disruption. Significant differences (* to ****) are evident from 15 min to 5 hours (An va corrected for multiple comparisons). In the lower panels, the correlation of EB disruption with clinically relevant outcomes such as length of hospital stay (b) and days of intensive care (c) are shown. Negative correlations (Spearman test) indicate that the magnitude of EB disruption is associated with worse outcomes. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Association of the angiopoietin/TIE2 and VEGF-a pathways with clinical and laboratory markers of disease severity incovid-19

Background : Endothelial barrier (EB) disruption is an important part of immunothrombosis, allowing the access of leukocytes to inflamed tissues. Pathways involving angiopoietin (Ang) 1 and 2 and their receptor Tie2, and VEGF-A/VE-cadherin (VEC) are key regulators of EB integrity. While the association of these mediators with sepsis severity have been known for more than 15 years, it was only recently that their role in coagulation activation was described. Moreover, these proteins also mediate angiogenesis, which has been shown to be upregulated in COVID-19. Aims : To measure circulating levels of key mediators of Ang/Tie2 and VEGF-A pathways in COVID-19 patients, and to explore their association with disease severity and hemostatic activation. Methods : Samples were obtained from patients admitted to a COVID-19 ward, within 24 h from COVID-19 confirmation. EB mediator levels were measured by immunological methods (Elisa or multiplex assays). The study was approved by the IRB and all participants provided written informed consent. Results : Data were obtained from 30 patients and 30 age and sexmatched healthy individuals. Mean length of hospital stay (LOS) was 12.9 ± 9.8 days respectively, twelve patients (40%) required intensive care (ICU), and 28/30 patients survived. Mean D-dimer was 3,609 ± 14,440 ng/mL. Levels of EB mediators are shown in Table 1. Associations between these parameters with relevant clinical and laboratory markers of disease severity are shown in Table 2. Conclusions : All mediators of EB disruption were significantly elevated in COVID-19 patients. In addition, these mediators were consistently associated with proteins involved in immunothrombosis, in particular with fibrinogen, VWF:Ag, uPAR, PAI-1 and P-selectin. Clinically significant associations were observed between Ang-2 and VEGF-A and extension of lung disease (for both) and ICU stay (for VEGF-A). Additional studies are warranted to explore the crosstalk between Ang/Tie2 and VEGF-A pathways with hemostasis in COVID-19.