Oral lesions in patients with COVID-19 hospitalized in an intensive care unit: a case-series study.

This study evaluated the presence of oral lesions in patients with COVID-19 hospitalized in an intensive care unit (ICU). Data included demographic, clinical, and laboratory information. Clinical assessment of the oral cavity was performed on the 2 nd and 5 th days of orotracheal intubation. Thirty-eight patients were evaluated and 16 (42.1%) presented oral lesions during their ICU stay. The median age and length of stay were 75 years and 15 days, respectively. Among the patients with oral lesions, ulcerative oral lesions were reported in 14 (87.5%) patients, of which 11 (78.6%) were found on the lips. This study highlights the importance of oral examination for patients admitted to the ICU with COVID-19.

Serum glial fibrillary acidic protein is a body fluid biomarker: A valuable prognostic for neurological disease - A systematic review.

Astrocytes are the most abundant cell type in the human central nervous system, and they play an important role in the regulation of neuronal physiology. In neurological disorders, astrocyte disintegration leads to the release of glial fibrillary acidic protein (GFAP) from tissue into the bloodstream. Elevated serum levels of GFAP can serve as blood biomarkers, and a useful prognostic tool to facilitate the early diagnosis of several neurological diseases ranging from stroke to neurodegenerative disorders. This systematic review synthesizes studies published between January 2012 and September 2021 that used GFAP as a potential blood biomarker to detect neurological disorders. The following electronic databases were accessed: MEDLINE, Scopus, and Web of Science. In all the databases, the following search strategy was used: ¨GFAP¨ OR ¨glial fibrillary acidic protein¨ AND ¨neurological¨ OR ¨neurodegenerative¨ AND ¨plasma¨ OR ¨serum¨. The initial search identified 1152 articles. After the exclusion criteria were applied, 48 publications that reported GFAP levels in neurological disorders were identified. A total of16 different neurological disorders that have plasmatic GFAP levels as a possible biomarker for the disease were described in the articles, being: multiple sclerosis, frontotemporal lobar degeneration, Alzheimer's disease, Parkinson disease, COVID-19, epileptic seizures, Wilson Disease, diabetic ketoacidosis, schizophrenia, autism spectrum disorders, major depressive disorder, glioblastoma, spinal cord injury, asthma, neuromyelitis optica spectrum disorder and Friedreich's ataxia. Our review shows an association between GFAP levels and the disease being studied, suggesting that elevated GFAP levels are a potentially valuable diagnostic biomarker in the evaluation of different neurological diseases.

Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity.

BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative stress that could be used as severity markers in respiratory viral infections such as COVID-19. However, there is a lack of clinical studies evaluating the role of oxidative stress-related molecules including glial fibrillary acidic protein (GFAP), the receptor for advanced glycation end products (RAGE), high mobility group box-1 protein (HMGB1) and cyclo-oxygenase-2 (COX-2) in COVID-19 pathogenesis. AIM: To evaluate the role of oxidative stress-related molecules in COVID-19. METHOD: An observational study with 93 Brazilian participants from September 2020 to April 2021, comprising 23 patients with COVID-19 admitted to intensive care unit (ICU), 19 outpatients with COVID-19 with mild to moderate symptoms, 17 individuals reporting a COVID-19 history, and 34 healthy controls. Blood samples were taken from all participants and western blot assay was used to determine the RAGE, HMGB1, GFAP, and COX-2 immunocontent. RESULTS: We found that GFAP levels were higher in patients with severe or critical COVID-19 compared to outpatients (p = 0.030) and controls (p < 0.001). A significant increase in immunocontents of RAGE (p < 0.001) and HMGB1 (p < 0.001) were also found among patients admitted to the ICU compared to healthy controls, as well as an overexpression of the inducible COX-2 (p < 0.001). In addition, we found a moderate to strong correlation between RAGE, GFAP and HMGB1 proteins. CONCLUSION: SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19.

Seroprevalence of SARS-CoV-2 IgM and IgG antibodies in an asymptomatic population in Sergipe, Brazil.

OBJECTIVE: To estimate the prevalence of SARS-CoV-2 antibodies in an asymptomatic population in the state of Sergipe, Brazil.
. METHODS: This cross-sectional study with stratified sampling (sex and age) included serological immunofluorescent tests for IgM and IgG on samples from 3 046 asymptomatic individuals. Sample collection was performed in wet-markets of the 10 most populous cities of Sergipe, Brazil. Exclusion criteria included symptomatic individuals and health workers. The presence of comorbidities was registered.
. RESULTS: Of the 3 046 participants, 1 577 (51.8%) were female and 1 469 (48.2%) were male; the mean age was 39.76 (SD 16.83) years old. 2 921 tests were considered valid for IgM and 2 635 for IgG. Of the valid samples, 347 (11.9% [CI 10.7%-13.1%]) tested positive for IgM and 218 (8.3% [CI 7.2%-9.4%]) tested positive for IgG. Women over 40 had the highest prevalence for IgM (group C, p=0.006; group D p=0.04). The capital Aracaju displayed the highest prevalence for both antibodies; 83 (26.3% [CI 21.6%-31.6%]) tested positive for IgM and 35 (14.6% [CI 10.4%-19.7%]) for IgG. The most prevalent comorbidities were hypertension (64/123 individuals) and diabetes (29/123).
. CONCLUSIONS: A high prevalence of SARS-CoV-2 antibodies was found among asymptomatic persons in Sergipe. Women over 40 showed the highest rates. The capital, Aracaju, displayed the highest seroprevalence. Surveys like this one are important to understand how the virus spreads and to help authorities to plan measures to control it. Repeated serologic testing are required to track the progress of the epidemic.

OBJETIVO: estimar la prevalencia de anticuerpos dirigidos contra el SARS-CoV-2 en una población asintomática del estado de Sergipe, Brasil. MÉTODOS: estudio transversal con muestreo estratificado (por sexo y edad) que incluyó pruebas serológicas de inmunofluorescencia para IgM e IgG en muestras de 3 046 individuos asintomáticos. La recolección de muestras se realizó en los mercados húmedos de las 10 ciudades más pobladas de Sergipe, Brasil. Se excluyó a los individuos sintomáticos y a los trabajadores de la salud. Se registró la presencia de comorbilidades. RESULTADOS: De los 3 046 participantes, 1 577 (51,8%) eran mujeres y 1 469 (48,2%) varones; la edad promedio fue de 39,76 (SD 16,83) años. Se consideraron válidas 2 921 pruebas para la IgM y 2 635 para la IgG. De las muestras válidas, 347 (11,9% [CI 10,7%-13,1%]) resultaron positivas para IgM y 218 (8,3% [CI 7,2%-9,4%]) para IgG. Las mujeres mayores de 40 años tuvieron la mayor prevalencia de IgM (grupo C, p=0,006; grupo D, p=0,04). Aracaju, la capital del estado, mostró la mayor prevalencia para ambos anticuerpos; 83 (26,3% [CI 21,6%-31,6%]) resultaron positivas para IgM y 35 (14,6% [CI 10,4%-19,7%]) para IgG. Las comorbilidades más frecuentes fueron la hipertensión (64/123 individuos) y la diabetes (29/123). CONCLUSIONES: Se encontró una alta prevalencia de anticuerpos contra el SARS-CoV-2 en personas asintomáticas en Sergipe. Las mujeres mayores de 40 años mostraron las tasas más altas. La capital, Aracaju, mostró la mayor seroprevalencia. Las encuestas como esta son importantes para comprender cómo se propaga el virus y para ayudar a las autoridades a planificar medidas de control. Se requieren pruebas serológicas repetidas para dar seguimento al progreso de la epidemia.

Efficacy and safety of hydroxychloroquine as pre-and post-exposure prophylaxis and treatment of COVID-19: A systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials.

BACKGROUND: Hydroxychloroquine (HCQ) is an anti-malarial and immunomodulatory drug considered a potential candidate for drug repurposing in COVID-19 due to their in vitro antiviral activity against SARS-CoV-2. Despite the potential antiviral effects and anti-inflammatory profile, the results based on clinical studies are contradictory. Therefore, the quality of the decision-making process from meta-analyses summarizing the available evidence selecting studies with different designs and unblinded trials is limited. The aim of this study was to synthesize the best evidence on the efficacy and safety of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19. METHODS: Searches were performed in PubMed, Web of Science, Embase, Lilacs, the website ClinicalTrials.gov and the preprint server medRxiv from January 1, 2020 to May 17, 2021. The following elements were used to define eligibility criteria: (1) Population: individuals at high-risk of exposure to SARS-CoV-2 (pre-exposure), individuals who had close contact with a positive or probable case of COVID-19 (post-exposure), non-hospitalized patients with COVID-19 and hospitalized patients with COVID-19; (2) Intervention: HCQ; (3) Comparison: placebo; (4) Outcomes: incidence of SARS-CoV-2 infection, need for hospitalization, length of hospital stay, need for invasive mechanical ventilation (MV), death, and adverse events; and (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Risk of bias was judged according to the Cochrane guidelines for RCTs. Treatment effects were reported as relative risk (RR) for dichotomous variables and mean difference (MD) for continuous variables with 95% confidence intervals (CI). We used either a fixed or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. The GRADE system was used to evaluate the strength of evidence between use of HCQ and the outcomes of interest. FINDINGS: Fourteen blinded, placebo-controlled RCTs were included in this meta-analysis. Four trials (1942 patients: HCQ = 1271; placebo = 671) used HCQ as a prophylactic medication pre-exposure to COVID-19, two (1650 patients: HCQ = 821; placebo = 829) as a prophylactic medication post-exposure to COVID-19, three (1018 patients: HCQ = 497; placebo = 521) as treatment for non-hospitalized patients, and five (1138 patients: HCQ = 572; placebo = 566) as treatment for hospitalized patients with COVID-19. We found no decreased risk of SARS-CoV-2 infection among individuals receiving HCQ as pre-exposure (RR = 0.90; 95% CI 0.46 to 1.77) or post-exposure (RR = 0.96; 95% CI 0.72 to 1.29) prophylaxis to prevent COVID-19. There was no significant decreased risk of hospitalization for outpatients with SARS-CoV-2 infection (RR = 0.64; 95% CI 0.33 to 1.23) and no decreased risk of MV (RR = 0.81; 95% CI 0.49 to 1.34) and death (RR = 1.05; 95% CI 0.62 to 1.78) among hospitalized patients with COVID-19 receiving HCQ. The certainty of the results on the lack of clinical benefit for HCQ was rated as moderate. Moreover, our results demonstrated an increased risk for any adverse events and gastrointestinal symptoms among those using HCQ. INTERPRETATION: Available evidence based on the results of blinded, placebo-controlled RCTs showed no clinical benefits of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19. FUNDING: There was no funding source.

Insights into the actions of angiotensin-1 receptor (AT1R) inverse agonists: Perspectives and implications in COVID-19 treatment.

New coronavirus SARS-CoV-2 (COVID-19) has caused chaos in health care systems. Clinical manifestations of COVID-19 are variable, with a complex pathophysiology and as yet no specific treatment. It has been suggested that the renin-angiotensin-aldosterone system has a possible role in the severity of cases and the number of deaths. Our hypothesis is that drugs with inverse agonist effects to the angiotensin-1 receptor can be promising tools in the management of patients with COVID-19, possibly avoiding complications and the poor evolution in some cases. Any risk factors first need to be identified, and the most appropriate time to administer the drugs during the course of the infection also needs to be established. Several angiotensin receptor blockers (ARB) have a favorable profile and are important candidates for the treatment of COVID-19. In this review we discussed a set of compounds with favorable profile for COVID-19 treatment, including azilsartan, candesartan, eprosartan, EXP3174, olmesartan, telmisartan, and valsartan. They are effective as inverse agonists and could reduce the "cytokine storm" and reducing oxidative stress. As COVID-19 disease has several evolution patterns, the effectiveness of ARB therapy would be related to infection "timing", patient risk factors, previous use of ARBs, and the specific molecular effects of an ARB. However, controlled studies are needed to identify whether ARBs are beneficial in the treatment of patients with COVID-19.

Delay in head and neck cancer care during the COVID-19 pandemic and its impact on health outcomes

The coronavirus disease 2019 (COVID-19) outbreak has created unprecedent challenges for healthcare systems worldwide. Oncology services have been reorganized to decrease the risk of nosocomial acquisition of SARS-CoV-2, but changes in treatment pathways and follow-up cancer care can result in patients receiving suboptimal or delayed care. Herein, we describe a cross-sectional nested cohort study conducted to evaluate delays in care for patients with head and neck cancer (HNC) in post-treatment follow-up or palliative care during the COVID-19 pandemic in Northeast Brazil and its impact on health outcomes. Information was extracted from medical records and supplemented by telephone interviews. We compared the following health outcomes: self-perception of anxiety or sadness, fear of COVID-19 infection, cancer-related complications during social isolation, self-medication, diagnosis of COVID-19, and death between patients with and without delayed cancer care. The Mann-Whitney U test was used to compare distributions of continuous variables and the Fisher exact test was used for categorical variables. Thirty-one HNC patients were included in the study, and no case of confirmed SARS-CoV-2 was found. Delayed cancer care due to restriction in health services was reported in 58.1% of cases, and there was no report of telemedicine use during the COVID-19 outbreak. Cancer-related complications during the COVID-19 pandemic were described for most patients (67.7%) and included pain or discomfort, swelling, and dyspnea. Eight (25.8%) patients reported use of prescribed morphine or codeine to manage pain and six (19.4%) patients reported self-medication with over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs). We found an association between delayed HNC care and the use of self-medication (p = 0.028). This study indicated that patients with delayed HNC care during the COVID-19 outbreak are more likely to use self-medication with NSAIDs for pain management. Better strategies to follow HNC patients in socioeconomically disadvantaged communities need to be discussed and implemented.

Delay in head and neck cancer care during the COVID-19 pandemic and its impact on health outcomes

The coronavirus disease 2019 (COVID-19) outbreak has created unprecedent challenges for healthcare systems worldwide. Oncology services have been reorganized to decrease the risk of nosocomial acquisition of SARS-CoV-2, but changes in treatment pathways and follow-up cancer care can result in patients receiving suboptimal or delayed care. Herein, we describe a cross-sectional nested cohort study conducted to evaluate delays in care for patients with head and neck cancer (HNC) in post-treatment follow-up or palliative care during the COVID-19 pandemic in Northeast Brazil and its impact on health outcomes. Information was extracted from medical records and supplemented by telephone interviews. We compared the following health outcomes: self-perception of anxiety or sadness, fear of COVID-19 infection, cancer-related complications during social isolation, self-medication, diagnosis of COVID-19, and death between patients with and without delayed cancer care. The Mann-Whitney U test was used to compare distributions of continuous variables and the Fisher exact test was used for categorical variables. Thirty-one HNC patients were included in the study, and no case of confirmed SARS-CoV-2 was found. Delayed cancer care due to restriction in health services was reported in 58.1% of cases, and there was no report of telemedicine use during the COVID-19 outbreak. Cancer-related complications during the COVID-19 pandemic were described for most patients (67.7%) and included pain or discomfort, swelling, and dyspnea. Eight (25.8%) patients reported use of prescribed morphine or codeine to manage pain and six (19.4%) patients reported self-medication with over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs). We found an association between delayed HNC care and the use of self-medication (p = 0.028). This study indicated that patients with delayed HNC care during the COVID-19 outbreak are more likely to use self-medication with NSAIDs for pain management. Better strategies to follow HNC patients in socioeconomically disadvantaged communities need to be discussed and implemented.