Alpha 1-acid glycoprotein is upregulated in severe COVID-19 patients and decreases neutrophil NETs in SARS-CoV-2 infection.

Orosomucoid, or alpha-1 acid glycoprotein (AGP), is a major acute-phase protein expressed in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. AGP's biological functions in coronavirus disease 2019 (COVID-19) are not understood. We sought to investigate the role of AGP in severe COVID-19 infection patients and neutrophils infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Epidemiological data, AGP levels, and other laboratory parameters were measured in blood samples from 56 subjects hospitalized in the ICU with SARS-CoV-2 infection. To evaluate the role of AGP in NETosis in neutrophils, blood samples from health patients were collected, and neutrophils were separated and infected with SARS-CoV-2. Those neutrophils were treated with AGP or vehicle, and NETosis was analyzed by flow cytometry. AGP was upregulated in severe COVID-19 patients (p<0.05). AGP level was positively correlated with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and negatively correlated with lactate (p=0.004). AGP treatment downregulated early and late NETosis (respectively, 35.7% and 43.5%) in neutrophils infected with SARS-CoV-2 and up-regulated IL-6 supernatant culture expression (p<0.0001). Our data showed increased AGP in COVID-19 infection and contributed to NETosis regulation and increased IL-6 production, possibly related to the Cytokine storm in COVID-19.

Caracterização dos sintomas na hospitalização de pacientes em cuidados paliativos / Caracterización de síntomas en la hospitalización de pacientes en cuidados paliativos / Characterization of symptoms in the hospitalization of patients in palliative care

Objetivo:avaliar a presença e intensidade dos sinais e sintomas de pacientes em cuidados paliativos nos três primeiros dias de internação. Método:estudo observacional, com pacientes adultos e idosos. Foi utilizado questionário para a coleta dos dados sociodemográficos e clínicos e um instrumento validado para a avaliação dos sinais e sintomas. Resultados:dentre os 50 participantes, a maioria é mulher (56%) com idade média de 66,7 anos e escolaridade de 6,1 anos. A principal doença de base foi câncer de pulmão (12%). Apresentaram elevados níveis de cansaço, sonolência, falta de apetite, depressão e ansiedade no primeiro dia de internação. No decorrer dos três dias de observação houve melhora em relação ao cansaço e à depressão e piora da sonolência. Conclusão:a assistência paliativa possui potencial para contribuir com o adequado manejo dos sintomas ao longo da internação, o que pode influenciar positivamente a qualidade de vida dos pacientes.

Objective:to evaluate the presence and intensity of signs and symptoms of patients in palliative care in the first three days of hospitalization. Method:observational, study with adult and elderly patients. A questionnaire was used to collect sociodemographic and clinical data and a validated instrument for the evaluation of signs and symptoms.Results:among the 50 participants, most are women (56%) with a mean age of 66.7 years and schooling of 6.1 years. The main underlying disease was lung cancer (12%). They presented high levels of tiredness, sleepiness, lack of appetite, depression, and anxiety on the first day of hospitalization. During the three days of observation, there was an improvement in terms of tiredness and depression and a worsening of sleepiness. Conclusion:palliative care has the potential to contribute to the adequate management of symptoms during hospitalization, which can positively influence patients' quality of life.

Objetivo:evaluar la presencia e intensidad de signos y síntomas de pacientes en cuidados paliativos en los tres primeros días de hospitalización. Método:estudio observacional, con pacientes, adultos y ancianos. Se utilizó cuestionario para recolectar datos socio demográficos, clínicos e instrumento validado para la evaluación de signos y síntomas. Resultados:entre los 50 participantes, la mayoría son mujeres (56%) con una edad media de 66,7 años y escolaridad de 6,1 años. La principal enfermedad de base fue el cáncer de pulmón (12%). Presentaron altos niveles de cansancio, somnolencia, inapetencia, depresión y ansiedad el primer día de hospitalización. Durante los tres días de observación, hubo una mejoría en términos de cansancio y depresión y un empeoramiento de la somnolencia. Conclusión:los cuidados paliativos tienen el potencial de contribuir al manejo adecuado de los síntomas durante la hospitalización, lo que puede influir positivamente en la calidad de vida de los pacientes.

Assessment of physicians' knowledge about brain death and organ donation and associated factors.

Precocity and assertiveness when diagnosing brain death are essential for identifying potential donors. To assess the knowledge of physicians about brain death and organ donation, cross-sectional web-based survey was carried out with physicians from different specialties. The knowledge about brain death and organ donation was assessed by a questionnaire with 12 multiple-choice or multiple-answer questions (possible range from 0 to 12). The nonparametric Mann-Whitney and Kruskal-Wallis tests were performed to verify the association between the physicians' knowledge and others variables. The project was approved by the Research Ethics Committee of the Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, under number 4.022.657, and all patients agreed to participate and provided free prior-informed consent. Three hundred sixty physicians were included in this study, most of them have postgraduate (55%) and 59.2% were intensive care physicians. The median of responses was 5 (obtained range from 0 to 10). The participants were classified in 2 groups: with satisfactory knowledge (scores above 5) or without satisfactory knowledge (scores equal/below 5). There was better performance among participants who: completed graduation between 6 and 10 years (P < .012); were intensive care physicians (P < .002); had participated in training courses (P < .001); and those who had worked in intensive care unit (ICU) from 6 to 10 years (P < .023); had performed over 10 brain death protocols (P < .001), and felt safe to talk to family members about brain death (P < .001). The results showed that the participants had low knowledge about diagnosis of brain death and organ donation protocols despite the majority working in ICUs. Be an intensive care physician, had large time experience in ICU, and had performed brain death protocols were associated with unsatisfactory knowledge concerning the subject.

MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients.

Respiratory symptoms are one of COVID-19 manifestations, and the metalloproteinases (MMPs) have essential roles in the lung physiology. We sought to characterize the plasmatic levels of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9) in patients with severe COVID-19 and to investigate an association between plasma MMP-2 and MMP-9 levels and clinical outcomes and mortality. MMP-2 and MMP-9 levels in plasma from patients with COVID-19 treated in the ICU (COVID-19 group) and Control patients were measured with the zymography. The study groups were matched for age, sex, hypertension, diabetes, BMI, and obesity profile. MMP-2 levels were lower and MMP-9 levels were higher in a COVID-19 group (p < 0.0001) compared to Controls. MMP-9 levels in COVID-19 patients were not affected by comorbidity such as hypertension or obesity. MMP-2 levels were affected by hypertension (p < 0.05), but unaffected by obesity status. Notably, hypertensive COVID-19 patients had higher MMP-2 levels compared to the non-hypertensive COVID-19 group, albeit still lower than Controls (p < 0.05). No association between MMP-2 and MMP-9 plasmatic levels and corticosteroid treatment or acute kidney injury was found in COVID-19 patients. The survival analysis showed that COVID-19 mortality was associated with increased MMP-2 and MMP-9 levels. Age, hypertension, BMI, and MMP-2 and MMP-9 were better predictors of mortality during hospitalization than SAPS3 and SOFA scores at hospital admission. In conclusion, a significant association between MMP-2 and MMP-9 levels and COVID-19 was found. Notably, MMP-2 and MMP-9 levels predicted the risk of in-hospital death suggesting possible pathophysiologic and prognostic roles.