T cell-mediated Immune response and correlates of inflammation and their relationship with COVID-19 clinical severity: not an intuitive guess.

BACKGROUND: Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19. METHODS: For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology. FINDINGS: CD4+ T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033). INTERPRETATION: Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles.

Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial.

BACKGROUND: The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates' drugs. Nitazoxanide (NTZ) has a broad antiviral effect. METHODS: This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. FINDINGS: Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+ T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+ T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01). INTERPRETATION: Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.

Corrigendum to "Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial." [EClinicalMedicine 37 (2021) 100981].

[This corrects the article DOI: 10.1016/j.eclinm.2021.100981.].

Estudo piloto de avaliação da influência do ultra-som na estabilidade do alfa-humuleno e trans-cariofileno presentes no fitomedicamento antiinflamatório, creme de Cordia verbenacea 5mg/g / Pilot study to evaluate the effects of ultrasound on the stability of alpha-humelene and trans-caryophyllene contained on an anti-inflammatory phytomedicine, Cordia verbenacea DC 5mg/g cream

O fitomedicamento antiinflamatório tópico obtido da Cordia verbenacea (5mg/g) possui eficácia e segurança clinicamente comprovadas. A fonoforese é uma técnica muito utilizada no tratamento de lesões dos tecidos moles. Desta maneira, o objetivo deste estudo foi avaliar a influência do ultra-som na estahilidade dos isômeros alfa-humuleno e trans-cariofileno, princípios ativos desse medicamento. Foram realizadas cinco simulações de fonoforese onde uma massa entre 8,79 a 10,88 gramas de medicamento era aplicada num modelo anatômico e submetida ao contato com ultra-som na freqüência de 100Hz, forma pulsátil de 50 por cento por um período de 5 a 10 minutos e potência de 1, 2 e 3 w/cm² de acordo com cada protocolo. 0: material foi recuperado e as análises químicas realizadas por Cromatografia Gasosa. Os teores dos ativos foram comparados aos teores do lote controle que não sofreu exposição ao ultra-som. Nas condições empregadas no trabalho, observou-se manutenção das concen-trações do a1fa-humuleno e trans-cariofileno após contato com vibrações ultra-sônicas

Síndrome de Mirizzi: relato de caso e revisäo de literatura / Mirizzi's syndrome: case report and literature review

A síndrome de Mirizzi constitui causa rara de icterícia obstrutiva. Apresentamos um caso de síndrome de Mirizzi em paciente de 42 anos, que se manifestou através de icterícia, colúria, hipocolia fecal, dor abdominal, prurido, picos febris e emagrecimento de 10Kg no período de um mês. O diagnóstico foi realizado no pré-operatório através de PCRE, que evidenciou cálculo de 1,6cm no ducto cístico, comprimindo extrinsecamente o ducto biliar comum. A paciente foi submetida a colecitectomia, näo apresentando intercorrências no pós-operatório