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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., (© 2024. The Author(s).)

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 20 th , 2020, to September 21 st , 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., Competing Interests: VB exerts activities of clinical research at FQM Farmoquímica, sponsor of the study. AL reports grants from FQM, during the conduct of the study; personal fees from Daiicho Sankyo Brasil, Pfizer, Mantecorp Indústria Química e Farmacêutica, Libs Farmacêutica, Sanofi-Aventis; grants, personal fees and non-financial support from Janssen Pharmaceutical; personal fees and non-financial support from Cristalia Produtos Químicos e Farmacêuticos; grants and personal fees from Eli Lilly; grants from H. Lundbeck A/S, Servier Laboratories, Hoffman-La Roche, Forum Pharmaceuticals, Biophytis, Ganentech, Cellavita, Celltrion (outside the submitted work). JG, DD, JH, and NM report personal fees from FMQ during the conduct of the study. SC reports grants from FQM during the conduct of the study; grants from MERCK SHARP & DOME, NOVARTIS, ROCHE, ABBVIE, GILEAD, and PFIZER (outside the submitted work). Other authors do not have any conflict of interest to declare., (© 2021 The Authors.)

Ribavirin in a fixed doses of 1.0 g/day was administered to 15 cirrhotic patients with portal hypertension and HCV-RNA detected in the blood by PCR during a six months period, in a non-controlled study. Two patients presented complications due to hepatic insufficiency and their data were not available at the end of the study. In four patients the hemoglobin levels fell below 20% of the initial value and in one the ribavirin dose had to be reduced. No other significant adverse reaction to the drug was observed. Almost all patients experienced a decrease in the aminotransferases levels during the study, specially in the first three months of treatment when the AST and ALT levels were significantly reduced when compared with the initial values. At the end of six months, four patients presented a complete response with normal aminotransferases levels, but only in one patient the HCV-RNA was not detected in the blood. In this patient the drug interruption was followed by elevation in aminotransferases levels and HCV-RNA detection in the blood 45 days later. Such results suggest that although well tolerated and inducing a transient decrease in AST and ALT, ribavirin alone administration is not able to erradicate virus C infection in patients with hepatic cirrhosis and portal hypertension.

In Brazil, hepatocellular carcinoma (HCC) is not a common tumour. Virus B hepatitis and cirrhosis play an important role in the development of HCC. The authors described 14 cases of HCC registered in our service during the last 33 months. PURPOSE--Evaluate clinical and laboratory aspects of the hepatocarcinoma treated in our service. MATERIAL--Fourteen patients evaluated between 1990 and 1993 were described. Ten were men the median age was 53 years. RESULTS--The main symptoms were: abdominal pain, weight loss and jaundice. Among the fourteen patients, 42% percent were positive for HBsAg, 0.7% for anti HCV and 57% were cirrhotic. Eighty percent had an advanced disease and serum alphafeto-protein was elevated in 92%. The patients underwent different kinds of treatment. Systemic chemotherapy was started in 5 patients, however without any response. Surgery was done in three patients, one underwent partial resection of the tumour and in the others a total resection was carried out. CONCLUSION--The hepatocarcinoma is rare in our service, eighty percent had advanced disease and 42% were positive for HBsAg.