COVID-19 infection rate and time spent at home: analysis of the beginning of the pandemic / Taxa de infecção por COVID-19 e tempo gasto em casa: análise do começo da pandemia / Tasa de infección por COVID-19 y tiempo en casa: análisis del inicio de la pandemia

Background and Objectives: Evidence suggests that the failure of epidemiological control impedes the resumption of socioeconomic activities. Therefore, this study aimed to describe epidemiological aspects and the pattern of mobility on each continent and to verify the association between the COVID-19 infection rate and time spent at home. Methods: We analyzed reports from Global Positioning System of 97 countries and their epidemiological indicators until May 27, 2020. Results: Cases of COVID-19 ranged from 22 to 1,745,803, and deaths ranged from 0 to 102,107. The highest rates per 100,000 population were observed in Europe and America. Approximately 54% of COVID-19 cases occurred in America and 51% of deaths in Europe. Countries reduced mobility in retail and recreation (-43.45%±20.42%), grocery and pharmacy (-17.95%±20.82%), parks (-18.77%±37.34%), transit stations (-43.09%±20.31%), workplaces (-21.74%±19.92%), and increased time spent at home (13.00%±8.80%). Linear regression showed that European inhabitants stayed at home less when compared those on the American continent (ß=-4.933, SE=0.976, p<.001). In addition, every unit increase in the infection rate per 100,000 population increased 0.005 points in the mean time spent at home (ß=0.005, SE=0.001, p<.001). Conclusions: We provide evidence that increased infection rate of COVID-19 is associated with increased length of stay at home. As a main lesson, COVID-19 showed that in the absence of pharmacological resources, government authorities need to act quickly to contain the spread of infectious diseases.(AU)

Justificativa e objetivos: Evidências sugerem que as dificuldades no controle epidemiológico impedem a retomada das atividades socioeconômicas. Diante disso, tivemos os objetivos de descrever aspectos epidemiológicos e o padrão de mobilidade em cada continente e verificar a associação entre a taxa de infecção por COVID-19 e o tempo de permanência em casa. Métodos: Analisamos relatórios de Global Positioning System de 97 países e seus indicadores epidemiológicos até 27 de maio de 2020. Resultados: Casos de COVID-19 variaram de 22 a 1.745.803, e as mortes variaram de 0 a 102.107. Maiores taxas por 100.000 habitantes foram observadas na Europa e América. Aproximadamente 54% dos casos de COVID-19 ocorreram na América e 51% dos óbitos na Europa. Os países reduziram a mobilidade no varejo e recreação (-43,45% ± 20,42%), mercearia e farmácia (-17,95%±20,82%), parques (-18,77%±37,34%), estações de trânsito (-43,09%±20,31%), locais de trabalho (-21,74%±19,92%), e aumentaram o tempo em casa (13,00% ± 8,80%). A regressão linear mostrou que os habitantes europeus ficaram menos tempo em casa do que os habitantes do continente americano (ß=-4,933, EP=0,976, p<0,001). Além disso, cada unidade de aumento na taxa de infecção por 100.000 habitantes aumentou 0,005 pontos no tempo médio de permanência em casa (ß=0,005, EP=0,001, p<0,001). Conclusões: Fornecemos evidências de que o aumento da taxa de infecção por COVID-19 está associado ao aumento do tempo de permanência em casa. Como lição principal, a COVID-19 mostrou que, na ausência de recursos farmacológicos, as autoridades governamentais precisam agir rapidamente para conter a propagação de doenças infecciosas.(AU)

Justificación y Objetivos: Dificultades en el control epidemiológico dificultan la reactivación de actividades socioeconómicas. Nuestros objetivos fueron describir aspectos epidemiológicos y el patrón de movilidad en cada continente y verificar la asociación entre tasa de infección por COVID-19 y duración de estancia en casa. Métodos: Examinamos informes del Global Positioning System de 97 países y sus indicadores epidemiológicos hasta 27 de mayo de 2020. Resultados: Casos de COVID-19 oscilaron entre 22 y 1.745.803, y muertes entre 0 y 102.107. Tasas más altas por 100.000 habitantes ocurrieron en Europa y América. Aproximadamente 54% de los casos de COVID-19 ocurrieron en América y 51% de las muertes en Europa. Los países redujeron la movilidad en comercio y recreación (-43,45%±20,42%), tienda de comestibles y farmacia (-17,95%±20,82%), parques (-18,77%±37,34%), estaciones de tránsito (-43,09%±20,31%), lugares de trabajo (-21,74%±19,92%), y aumentaron la duración de la estancia en casa (13,00%±8,80%). La regresión lineal (R²=0,906) mostró que los europeos permanecían menos tiempo en casa en comparación con los del continente americano (ß=-4,933, EE=0,976, p<0,001). Además, cada unidad de aumento de la tasa de infección por 100.000 habitantes aumentó la duración media de la estancia en casa en 0,005 puntos (ß=0,005, EE=0,001, p<0,001). Conclusiones: Mostramos que el aumento de la tasa de infección de COVID-19 se asocia con una mayor duración de la estancia en casa. Como lección clave, COVID-19 demostró que, en ausencia de recursos farmacológicos, las autoridades gubernamentales deben actuar rápidamente para contener la propagación de enfermedades infecciosas.(AU)

Alterations in CD39/CD73 Axis of T cells associated with COVID-19 severity (preprint)

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in COVID-19 patients. Lower plasma ATP and adenosine levels were identified in mild and severe COVID-19 patients associated with proinflammatory cytokine profiles compared to healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+CD25+CD39+ (activated/memory Treg) and CD4+CD25+CD39+CD73+ T cells, and increased frequencies of high differentiated (CD27-CD28-) CD8+T cells compared to health controls. Severe COVID-19 patients also showed higher frequencies of CD4+CD39+, CD4+CD25-CD39+ (memory T effector cell), high differentiated CD8+ T cells (CD27-CD28-) and diminished frequencies of CD4+CD73+, CD4+CD25+CD39+ mTreg, CD4+CD25+CD39+CD73+, CD8+CD73+ and low-differentiated CD8+ T cells (CD27+CD28+) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+Annexin-V+ and CD8+Annexin-V+ T cells, showing increased T cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of PBMC from severe COVID-19 patients with adenosine reduced the NF-kB activation in T cells and monocytes. Together, these data add new knowledge regarding the immunopathology of COVID-19 through purinergic regulation, especially concerning adenosine deficiency. Brief Commentary Background Host factors modulates the type and the strength of the immune response during the viral infection, as well as the disease outcomes. However, to date, the role of purinergic signaling in SARS-CoV-2 infection remains unclear. We sought to evaluate alterations in extracellular adenine nucleotides and CD39/CD73 axis in T cells and their relationship with acute COVID-19 immunopathogenesis. Translational Significance COVID-19 patients present lower extracellular ATP and adenosine levels associated with altered CD39 and CD73 expression in CD4+ and CD8+ T cells. Purinergic signaling correlated with alterations in the differentiation status of CD8+ T cells, lymphocyte mitochondrial membrane polarization and T cell apoptosis. Our demonstration of the lower NF-κB activation in T cells and monocytes after in vitro adenosine treatment may indicate the regulatory effect of adenosine in the inflammation and cytokine storm of COVID-19. This study adds new knowledge regarding the immunopathology of COVID-19 through purinergic regulation.

Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients (preprint)

This study aimed to evaluate the link between microbial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR+ infected patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19+ patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, LPS concentrations and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-β1, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, increased microbial translocation during hospitalization coexist with the inflammatory condition of SARS-CoV-2 infection and could lead to higher monocyte activation in non-survivors COVID-19 patients.

Genetically Modified Mesenchymal Stromal/Stem Cells: Application in Critical Illness.

Critical illnesses including sepsis, acute respiratory distress syndromes, ischemic cardiovascular disorders and acute organ injuries are associated with high mortality, morbidity as well as significant health care system expenses. While these diverse conditions require different specific therapeutic approaches, mesenchymal stem/stromal cell (MSCs) are multipotent cells capable of self-renewal, tri-lineage differentiation with a broad range regenerative and immunomodulatory activities, making them attractive for the treatment of critical illness. The therapeutic effects of MSCs have been extensively investigated in several pre-clinical models of critical illness as well as in phase I and II clinical cell therapy trials with mixed results. Whilst these studies have demonstrated the therapeutic potential for MSC therapy in critical illness, optimization for clinical use is an ongoing challenge. MSCs can be readily genetically modified by application of different techniques and tools leading to overexpress or inhibit genes related to their immunomodulatory or regenerative functions. Here we will review recent approaches designed to enhance the therapeutic potential of MSCs with an emphasis on the technology used to generate genetically modified cells, target genes, target diseases and the implication of genetically modified MSCs in cell therapy for critical illness.