Guidelines for prophylaxis and anti-thrombotic treatment for patients with COVID-19. Consensus of the Latin American Cooperative Group on Hemostasis and Thrombosis (CLAHT) / Guía de profilaxia y tratamiento antitrombótico para pacientes con COVID-19. Consenso del Grupo Cooperativo Latinoamericano en Hemostasia y Trombosis (CLAHT)

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.

La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.

Environmental education in Portuguese Speaking Nations: a survey of current practices and priorities

Since the Community of Portuguese Speaking Nations (CPLP) was created in 1996, environmental education (EE) has gained recognition for enhancing multilateral cooperation on environmental protection and sustainability promotion. Conducted online in 2020 in all member states during the COVID-19 pandemic, this second Environmental Education Survey of CPLP explores the conditions and approaches of EE within the overall setting of the 2030 UN Agenda, taking the concepts of Canaparo's geo-epistemology and Öhman and Östman's selective traditions as the underlying framework of analysis. The survey received 196 valid responses from EE Experts and Promoters who hold positions in various institutional backgrounds. Addressing the current state of EE in all nine countries, a picture emerges of significant and ecologically prudent human intervention based on fact-based, normative, and pluralist EE approaches. Most encouraging is the overall finding that EE is vibrant, relevant for sustainable transformation, young people focussed, and in good heart.

Environmental education in Portuguese Speaking Nations: a survey of current practices and priorities

Since the Community of Portuguese Speaking Nations (CPLP) was created in 1996, environmental education (EE) has gained recognition for enhancing multilateral cooperation on environmental protection and sustainability promotion. Conducted online in 2020 in all member states during the COVID-19 pandemic, this second Environmental Education Survey of CPLP explores the conditions and approaches of EE within the overall setting of the 2030 UN Agenda, taking the concepts of Canaparo’s geo-epistemology and Öhman and Östman’s selective traditions as the underlying framework of analysis. The survey received 196 valid responses from EE Experts and Promoters who hold positions in various institutional backgrounds. Addressing the current state of EE in all nine countries, a picture emerges of significant and ecologically prudent human intervention based on fact-based, normative, and pluralist EE approaches. Most encouraging is the overall finding that EE is vibrant, relevant for sustainable transformation, young people focussed, and in good heart. [ FROM AUTHOR]

Chronic diseases, chest computed tomography, and laboratory tests as predictors of severe respiratory failure and death in elderly Brazilian patients hospitalized with COVID-19: a prospective cohort study.

BACKGROUND: The primary risk factors for severe respiratory failure and death in the elderly hospitalized with COVID-19 remain unclear. OBJECTIVE: To determine the association of chronic diseases, chest computed tomography (CT), and laboratory tests with severe respiratory failure and mortality in older adults hospitalized with COVID-19. METHOD: This was a prospective cohort with 201 hospitalized older adults with COVID-19. Chronic diseases, chest CT, laboratory tests, and other data were collected within the first 48 h of hospitalization. Outcomes were progression to severe respiratory failure with the need of mechanical ventilation (SRF/MV) and death. RESULTS: The mean age was 72.7 ± 9.2 years, and 63.2% were men. SRF/MV occurred in 16.9% (p < 0.001), and death occurred in 8%. In the adjusted regression analyses, lung involvement over 50% [odds ratio (OR): 3.09 (1.03-9.28; 0.043)], C-reactive protein (CRP) > 80 ng/mL [OR: 2.97 (0.99-8.93; 0.052)], Vitamin D < 40 ng/mL [OR: 6.41 (1.21-33.88; 0.029)], and hemoglobin < 12 g/mL [OR: 3.32 (1.20-9.20; 0.020)] were independent predictors for SFR/MV, while chronic atrial fibrillation [OR: 26.72 (3.87-184.11; 0.001)], cancer history [OR:8.32 (1.28-53.91; 0.026)] and IL-6 > 40 pg/mL [OR:10.01 (1.66-60.13; 0.012)] were independent predictors of death. CONCLUSION: In hospitalized older adults with COVID-19, tomographic pulmonary involvement > 50%, anemia, vitamin D below 40 ng/mL, and CRP above 80 mg/L were independent risk factors for progression to SRF/MV. The presence of chronic atrial fibrillation, previous cancer, IL-6 > 40 pg/mL, and anemia were independent predictors of death.

pyKVFinder: an efficient and integrable Python package for biomolecular cavity detection and characterization in data science.

BACKGROUND: Biomolecular interactions that modulate biological processes occur mainly in cavities throughout the surface of biomolecular structures. In the data science era, structural biology has benefited from the increasing availability of biostructural data due to advances in structural determination and computational methods. In this scenario, data-intensive cavity analysis demands efficient scripting routines built on easily manipulated data structures. To fulfill this need, we developed pyKVFinder, a Python package to detect and characterize cavities in biomolecular structures for data science and automated pipelines. RESULTS: pyKVFinder efficiently detects cavities in biomolecular structures and computes their volume, area, depth and hydropathy, storing these cavity properties in NumPy arrays. Benefited from Python ecosystem interoperability and data structures, pyKVFinder can be integrated with third-party scientific packages and libraries for mathematical calculations, machine learning and 3D visualization in automated workflows. As proof of pyKVFinder's capabilities, we successfully identified and compared ADRP substrate-binding site of SARS-CoV-2 and a set of homologous proteins with pyKVFinder, showing its integrability with data science packages such as matplotlib, NGL Viewer, SciPy and Jupyter notebook. CONCLUSIONS: We introduce an efficient, highly versatile and easily integrable software for detecting and characterizing biomolecular cavities in data science applications and automated protocols. pyKVFinder facilitates biostructural data analysis with scripting routines in the Python ecosystem and can be building blocks for data science and drug design applications.

Multifactorial Basis and Therapeutic Strategies in Metabolism-Related Diseases.

Throughout the 20th and 21st centuries, the incidence of non-communicable diseases (NCDs), also known as chronic diseases, has been increasing worldwide. Changes in dietary and physical activity patterns, along with genetic conditions, are the main factors that modulate the metabolism of individuals, leading to the development of NCDs. Obesity, diabetes, metabolic associated fatty liver disease (MAFLD), and cardiovascular diseases (CVDs) are classified in this group of chronic diseases. Therefore, understanding the underlying molecular mechanisms of these diseases leads us to develop more accurate and effective treatments to reduce or mitigate their prevalence in the population. Given the global relevance of NCDs and ongoing research progress, this article reviews the current understanding about NCDs and their related risk factors, with a focus on obesity, diabetes, MAFLD, and CVDs, summarizing the knowledge about their pathophysiology and highlighting the currently available and emerging therapeutic strategies, especially pharmacological interventions. All of these diseases play an important role in the contamination by the SARS-CoV-2 virus, as well as in the progression and severity of the symptoms of the coronavirus disease 2019 (COVID-19). Therefore, we briefly explore the relationship between NCDs and COVID-19.

Incidence, diagnosis, treatment methods, and outcomes of clinically suspected venous thromboembolic disease in patients with COVID-19 in a quaternary hospital in Brazil.

BACKGROUND: Prothrombotic states have been associated with viral infections and the novel Sars-COV-2 infection has been associated with elevated D-dimer levels, although no causal relation has been clearly established. OBJECTIVES: This study presents an epidemiological analysis of manifest VTE episodes in a group of patients hospitalized because of COVID-19. METHODS: Medical records of patients who presented symptomatic deep vein thrombosis and/or pulmonary embolism in concomitance with confirmed COVID-19 were retrospectively studied. Demographic characteristics, prevalence of VTE, site of occurrence, D-dimer variation over time, management, and outcomes were analyzed. RESULTS: During the study period, 484 confirmed cases of COVID-19 were admitted, 64 of which displayed VTE symptoms and 13 of which had confirmed symptomatic VTE(2.68% of total sample and 20.31% of symptomatic cases). Most cases (76.92%) occurred in intensive care. On the day attributed to VTE onset, D-dimer levels were over 3,000 ng/mL in 8 (80%) patients, a significant increase from baseline admission levels (p < 0.05). A significant decrease was also observed in D-dimer values at hospital discharge (p < 0.05). All patients received pharmacological thromboprophylaxis and/or anticoagulation as indicated. Two deaths occurred during the study, both patients with severe comorbidities. At the end of our study protocol, nine patients had been discharged and two remained hospitalized, but had no signs of VTE worsening. CONCLUSIONS: VTE prevalence in hospitalized COVID-19 patients was 2.7%, and higher in intensive care units. Early institution of prophylaxis and immediate full anticoagulation when VTE is diagnosed should be the goals of those who treat this kind of patient.

CONTEXTO: Os estados pró-trombóticos têm sido associados a infecções virais. A nova infecção pela síndrome respiratória aguda grave do coronavírus 2 (SARS-CoV-2) sabidamente eleva os níveis de D-dímero, embora a relação causal não tenha sido bem estabelecida. OBJETIVOS: Este estudo apresenta uma análise epidemiológica de episódios sintomáticos de tromboembolismo em um grupo de pacientes hospitalizados pela doença do novo coronavírus (COVID-19). MÉTODOS: Foi realizada uma revisão retrospectiva de prontuários de pacientes internados por COVID-19 que apresentaram trombose venosa profunda e/ou embolia pulmonar sintomáticas. Foram avaliados os dados demográficos, a prevalência de tromboembolismo, a variação do D-dímero ao longo do tempo, o manejo e os desfechos. RESULTADOS: Dos 484 casos confirmados de COVID-19 admitidos entre março e julho de 2020, 64 apresentaram sintomas de tromboembolismo, que foram investigados, e 13 tiveram tromboembolismo confirmado (2,68% do total e 20,31% dos sintomáticos). A maioria dos casos ocorreu em regime de terapia intensiva (76,92%). Houve um aumento significativo no número de pacientes com D-dímero acima de 3.000 ng/mL no dia atribuído ao diagnóstico de tromboembolismo com relação aos níveis do momento da admissão (80%, p < 0,05).Uma queda significativa de pacientes nesse limiar também foi observada no momento da alta (p < 0,05). Todos os pacientes receberam tromboprofilaxia ou anticoagulação conforme indicado. Houve dois óbitos na amostra, ambos pacientes com comorbidades severas. Ao fim do protocolo, nove pacientes receberam alta e dois permaneceram hospitalizados, mas sem sinais de piora. CONCLUSÕES: A prevalência de tromboembolismo em pacientes hospitalizados por COVID-19 foi de 2,7%, sendo mais frequente em regime de terapia intensiva. A instituição precoce de profilaxia e anticoagulação imediata ao diagnóstico é primordial nesse grupo de pacientes.

Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy

ABSTRACT Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy

ABSTRACT Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection

ABSTRACT In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation). RESUMO Em dezembro de 2019, uma série de pacientes com pneumonia grave foi identificada em Wuhan, província de Hubei, na China. Esses pacientes evoluíram para síndrome respiratória aguda grave e síndrome do desconforto respiratório agudo. Posteriormente, a COVID-19 foi atribuída a um novo betacoronavírus, o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Cerca de 20% dos pacientes com diagnóstico de COVID-19 desenvolvem formas graves da doença, incluindo insuficiência respiratória aguda hipoxêmica, síndrome respiratória aguda grave, síndrome do desconforto respiratório agudo e insuficiência renal aguda e requerem admissão em unidade de terapia intensiva. Não há nenhum ensaio clínico randomizado controlado que avalie potenciais tratamentos para pacientes com infecção confirmada pela COVID-19 no momento da publicação destas recomendações de tratamento. Dessa forma, essas recomendações são baseadas predominantemente na opinião de especialistas (grau de recomendação de nível C).

Coagulation profile of COVID-19 patients admitted to the ICU: An exploratory study.

BACKGROUND: Coagulation abnormalities in COVID-19 patients have not been addressed in depth. OBJECTIVE: To perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19. METHODS: Conventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10. RESULTS: Thirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM-FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ​​than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability. CONCLUSION: COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system.

Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adults with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks / Consenso colombiano para la prevención, el diagnóstico y el tratamiento de condiciones trombóticas en adultos con COVID-19: aplicando el Marco de la Evidencia a la Decisión (EtD) GRADE

Introducción estudios recientes han reportado fenómenos trombóticos o coagulopatía en pacientes con COVID-19. Hay posiciones divergentes en cuanto a la prevención, el diagnóstico y el tratamiento de estos fenómenos, y la práctica clínica actual está basada únicamente en deducciones por extensión a partir de estudios retrospectivos, series de casos, estudios observacionales y guías internacionales desarrolladas previas a la pandemia. Objetivo establecer una serie de recomendaciones sobre prevención, diagnóstico y manejo de las complicaciones trombóticas asociadas a COVID-19. Métodos se desarrolló una guía rápida en la que se aplicó el marco de la evidencia a la decisión (EtD) de GRADE y un sistema de participación iterativo, con análisis estadísticos y cualitativos de sus resultados. Resultados se generaron 31 recomendaciones clínicas enfocadas a: a) Pruebas de coagulación en adultos sintomáticos con sospecha de infección o infección confirmada por SARS-CoV-2; b) Tromboprofilaxis en personas adultas con diagnóstico de COVID-19 (escalas de riesgo, tromboprofilaxis de manejo ambulatorio, intrahospitalario y duración de tromboprofilaxis después del egreso de hospitalización), c) Diagnóstico y tratamiento de las complicaciones trombóticas y d) Manejo de personas con indicación previa a usar agentes anticoagulantes. Conclusiones las recomendaciones clínicas de este consenso orientan la toma de decisiones clínicas respecto a prevención, diagnóstico y tratamiento de fenómenos trombóticos en pacientes con COVID-19, y representan un acuerdo que ayudará a disminuir la dispersión en las prácticas clínicas acorde con el desafío que impone la pandemia.

Abstract Introduction: recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. Objective: to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: a rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.

Evidence-Based Practical Guidance for the Antithrombotic Management in Patients With Coronavirus Disease (COVID-19) in 2020.

This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection.

In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).