Molecular and Cellular Biomarkers of COVID-19 Prognosis: Protocol for the Prospective Cohort TARGET Study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, the world's attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. OBJECTIVE: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19. METHODS: To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction-confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care. RESULTS: The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase. CONCLUSIONS: This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008). TRIAL REGISTRATION: Brazilian Registry of Clinical Trials RBR-62zdkk; https://ensaiosclinicos.gov.br/rg/RBR-62zdkk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24211.

The challenge of concomitant infections in the coronavirus disease 2019 pandemic era: Severe acute respiratory syndrome coronavirus 2 infection in a patient with chronic Chagas disease and dimorphic leprosy.

Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines.

The challenge of concomitant infections in the coronavirus disease 2019 pandemic era: Severe acute respiratory syndrome coronavirus 2 infection in a patient with chronic Chagas disease and dimorphic leprosy

Abstract Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines.

Pre-operative anesthetic assessment of patients with rheumatoid arthritis.

The management and surgical interventions of problems directly or indirectly arising from rheumatoid arthritis vary drastically. Anesthesiologists and rheumatologists should be aware of the peculiarities of the anesthetic preoperative assessment of these patients, including the assessment of possible disorders of the airways, in addition to the intra-operative management and analysis of relevant pharmacological parameters. It is critical that the anesthetist is familiar with the peculiarities of the disease and the specific characteristics of drugs used in its treatment: thus, he/she will be able to plan the best possible anesthetic technique for the surgery in question, offering safety and comfort to his/her patient. It is up to the rheumatologist to know the procedure to which the patient will be submitted to and be aware of the most appropriate anesthetic technique in each case. This will allow a better interaction between the rheumatologist and the anesthesiologist in the pre-anesthetic evaluation, through the sharing of relevant information on the articular and systemic involvement by the disease that might interfere with preoperative and intraoperative management. Furthermore, the information on the pre-anesthetic assessment and the choice of anesthetic technique will enable the rheumatologist to clarify any doubts that his/her patient and family may have, as well as to guide them as to whether or not the medications in use should be maintained, and eventually about the need for a supplemental dose of corticosteroid. The objective of this review is to acquaint the rheumatologist with key concepts related to the anesthetic preoperative assessment of patients diagnosed with RA, mainly including general notions that dictate the choice of the anesthetic technique.

Avaliação anestésica pré-operatória de pacientes com artrite reumatoide / Pre-operative anesthetic assessment of patients with rheumatoid arthritis

O manejo e as intervenções cirúrgicas de problemas decorrentes direta ou indiretamente da artrite reumatoide variam drasticamente. O anestesiologista e o reumatologista devem estar atentos às peculiaridades da avaliação anestésica pré-operatória desses pacientes, incluindo a avaliação de possíveis distúrbios das vias aéreas, além do manejo intraoperatório e da análise dos parâmetros farmacológicos pertinentes. É essencial que o médico anestesiologista esteja familiarizado com as peculiaridades da doença e com as características específicas dos medicamentos usados no seu tratamento, pois, assim, ele poderá planejar da melhor forma possível a técnica anestésica para o ato cirúrgico em questão, oferecendo segurança e conforto ao paciente. Ao reumatologista, cabe conhecer o procedimento a que o paciente será submetido e ter noção da técnica anestésica mais indicada em cada caso. Isso permitirá melhor interação entre o reumatologista e o anestesiologista na avaliação pré-anestésica, através do compartilhamento de informações relevantes sobre o acometimento articular e sistêmico pela doença que possam interferir com o manejo pré e intraoperatório. Além disso, as informações sobre a avaliação pré-anestésica e a escolha da técnica de anestesia contribuirão para que o reumatologista possa esclarecer dúvidas que o paciente e seus familiares porventura apresentem, bem como orientá-los quanto à manutenção ou não das medicações em uso e, eventualmente, da necessidade de suplementação da dose do corticosteroide. O objetivo desta revisão é familiarizar o reumatologista com os principais conceitos relacionados à avaliação anestésica pré-operatória de pacientes com diagnóstico de AR, incluindo, principalmente, as noções gerais que ditam a escolha da técnica anestésica.

The management and surgical interventions of problems directly or indirectly arising from rheumatoid arthritis vary drastically. Anesthesiologists and rheumatologists should be aware of the peculiarities of the anesthetic preoperative assessment of these patients, including the assessment of possible disorders of the airways, in addition to the intra-operative management and analysis of relevant pharmacological parameters. It is critical that the anesthetist is familiar with the peculiarities of the disease and the specific characteristics of drugs used in its treatment: thus, he/she will be able to plan the best possible anesthetic technique for the surgery in question, offering safety and comfort to his/her patient. It is up to the rheumatologist to know the procedure to which the patient will be submitted to and be aware of the most appropriate anesthetic technique in each case. This will allow a better interaction between the rheumatologist and the anesthesiologist in the pre-anesthetic evaluation, through the sharing of relevant information on the articular and systemic involvement by the disease that might interfere with preoperative and intraoperative management. Furthermore, the information on the pre-anesthetic assessment and the choice of anesthetic technique will enable the rheumatologist to clarify any doubts that his/her patient and family may have, as well as to guide them as to whether or not the medications in use should be maintained, and eventually about the need for a supplemental dose of corticosteroid. The objective of this review is to acquaint the rheumatologist with key concepts related to the anesthetic preoperative assessment of patients diagnosed with RA, mainly including general notions that dictate the choice of the anesthetic technique.

Differing phagocytic function of monocytes and neutrophils in Chagas' cardiopathy according to the presence or absence of congestive heart failure

A função fagocitária e a produção de radicais microbicidas de oxigênio pelos monócitos e neutrófilos foram avaliadas em 9 pacientes com cardiopatia chagásica com insuficiência cardíaca congestiva e 9 sem a síndrome em comparação com 11 indivíduos controles normais pelo teste de fagocitose de Saccharomyces cerevisiae e redução do nitroblue tetrazolium pelos fagócitos do sangue periférico. O índice fagocitário dos monócitos dos chagásicos sem insuficiência cardíaca foi significantemente 6,7 e 10,6 vezes menor do que o dos controles e chagásicos com a síndrome congestiva, respectivamente, devido ao menor envolvimento na fagocitose e a menor capacidade destas células de ingerirem partículas. Nos chagásicos sem insuficiência cardíaca os neutrófilos também apresentaram o IF 11,2 e 19,8 vezes menor que os controles e chagásicos com insuficiência cardíaca, respectivamente. A porcentagem de redução do NBT foi normal e similar para os três grupos. Efeitos opostos equilibrados das disfunções devidas às alterações cardiovasculares e imunes podem ter atuado nos pacientes chagásicos com insuficiência cardíaca paradoxalmente recuperando a função fagocitária alterada.

Differing phagocytic function of monocytes and neutrophils in Chagas' cardiopathy according to the presence or absence of congestive heart failure.

We evaluated the in vitro phagocytic function and the production of microbicidal oxygen radicals by monocytes and neutrophils of 9 Chagas' heart disease subjects with heart failure and 9 without the syndrome in comparison with 11 healthy subjects, by assessing phagocytosis of Saccharomyces cerevisiae and NBT reduction by peripheral blood phagocytes. Phagocytic index of monocytes of chagasics without heart failure was significantly 6.7 and 10.6 times lower than those of controls and chagasics with the congestive syndrome, respectively, due to a lesser engagement in phagocytosis and to an inability of these cells to ingest particles. Neutrophils also show in chagasics without heart failure PI 11.2 and 19.8 times lower than that of controls and chagasics with heart failure, respectively. The percent of NBT reduction was normal and similar for the three groups. Balanced opposite effects of cardiovascular and immune disturbances may be acting in Chagas' disease subjects with heart failure paradoxically recovering the altered phagocytic function.

Digitalis inhibits and furosemide does not change the in vitro phagocytic function of neutrophils of healthy subjects.

This work evaluated the in vitro influence of digitalis and furosemide on the phagocytic function of neutrophils of healthy individuals. Phagocytosis of Saccharomyces cerevisiae by peripheral blood neutrophils of 20 healthy individuals was assessed in the absence or presence of deslanoside or furosemide. The Wilcoxon test was employed to compare the data expressed as median and extreme values. Digitalis reduced the number of yeasts ingested by neutrophils (2.23, 1.23-4.01 versus 1.89, 0.87-2.79; p = 0.019). It did not influence the percentage of these cells engaged in phagocytosis, although there was a tendency for reduction (71%, 23-95% versus 57%, 8-93%; p = 0.11), which resulted in decreasing the phagocytic index from 192 (30-381) to 125 (10-218) (p = 0.028). Furosemide had no significant influence on the number of S. cerevisiae phagocytosed (2.23, 1.23-4.01 versus 1.96, 0.70-4.45; p = 0.89), the percent of phagocytosing neutrophils (71%, 23-95% versus 73%, 9-96%; p = 0.86) and the phagocytic index (192, 30-381 versus 152, 10-428; p = 0.95). These findings indicate the inhibitory influence of digitalis on in vitro neutrophil phagocytic function of healthy subjects, and suggest that this effect might impair the innate immune defense response. On this basis, they could contribute to improve digitalis therapy and advise that this drug class should not be associated with other drugs that may also impair the immune function, or might be used with caution or even avoided in subjects with infections.