Despite direct viral effect, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore, tocilizumab (TOC), a monoclonal antibody against IL-6 receptors, was considered as a possible therapeutic option. Patients were selected from the SARSTer database, containing 2332 individuals with COVID-19. Current study included 825 adult patients with moderate to severe course. Analysis was performed in 170 patients treated with TOC and 655 with an alternative medication. The end-points of treatment effectiveness were death rate, need for mechanical ventilation, and clinical improvement. Patients treated with TOC were balanced compared to non-TOC regarding gender, age, BMI, and prevalence of coexisting conditions. Significant effect of TOC on death was demonstrated in patients with baseline IL-6 > 100 pg/mL (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.08–0.57). The best effectiveness of TOC was achieved in patients with a combination of baseline IL-6 > 100 pg/mL and either SpO2 ≤ 90% (HR: 0.07) or requiring oxygen supplementation (HR: 0.18). Tocilizumab administration in COVID-19 reduces mortality and speeds up clinical improvement in patients with a baseline concentration of IL-6 > 100 pg/mL, particularly if they need oxygen supplementation owing to the lower value of SpO2 ≤ 90%.

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Background and Aim. The development of interferon- (IFN-) free regimens substantially improved efficacy of treatment for HCV, but despite excellent effectiveness the failures still occur. The aim of our study was to evaluate the efficacy of retreatment with genotype specific direct acting antivirals- (DAA-) based regimens in nonresponders to previous IFN-free therapy. Materials and Methods. Analysed population consisted of 31 nonresponders to IFN-free regimen, which received second IFN-free rescue therapy, selected from 6228 patients included in a national database EpiTer-2. Results. Age and gender distribution were similar, whereas proportion of genotype 1b was slightly higher and genotype 4 lower in the whole population compared to studied one. Patients included in the study demonstrated much more advanced fibrosis. Primary therapy was discontinued in 12 patients, which were recognized as failures due to nonvirologic reason, whereas virologic reason of therapeutic failure was recognized in 19 patients which completed therapy. Overall sustained virologic response (SVR) rate was 81% and 86% in intent-to-treat (ITT) and modified ITT analysis, respectively (74% and 78% in virologic failures, 92% and 100% in nonvirologic failures). Resistance-associated substitutions (RAS) testing was carried out in 8 patients from the group of completed primary therapy and three of them had potential risk for failure of rescue therapy due to NS5A association, while two of them achieved SVR. Conclusions. We demonstrated moderate effectiveness of genotype specific rescue therapy in failures due to virologic reason and high in those who discontinued primary therapy. Therefore rescue therapy with genotype specific regimens should be considered always if more potent regimens are not available.

The purpose of this study was to evaluate retinal and choroidal microvascular alterations with optical coherence tomography angiography (OCTA) in COVID-19 patients hospitalized because of bilateral pneumonia caused by SARS-CoV-2. The vessel density (VD) and foveal avascular zone (FAZ) of 63 patients with SARS-CoV-2 pneumonia who had positive polymerase chain reaction (PCR) tests and who recovered after receiving treatment and 45 healthy age- and gender-matched controls were evaluated and compared using OCTA in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The VD was also estimated in both groups in the choriocapillaris (CC). In COVID-19 patients, there was a statistically significant difference between the patients and a control group in both superficial (FAZs) and deep (FAZd) avascular zone (p = 0.000). The VD was significantly lower in the foveal area in choriocapillaris (p = 0.046). There were no statistically significant changes in the VD in the superior, inferior, nasal, and temporal quadrants in superficial and deep plexus, or in the choriocapillaris. The VD was not significantly lower in the foveal area in superficial or deep plexus. COVID-19 may affect the retinal vasculature, causing ischemia, enlargement of the FAZ, and lowering of the VD in the choriocapillaris area. Routine ophthalmic examination after SARS-CoV-2 infection should be considered in the course of post-infectious rehabilitation.

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Background and Aims:The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct-acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real-world experience, our study aimed to assess the efficacy and safety of 8-week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT). Methods: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer-2 database, large retrospective national real-world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers. Results: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0-F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT-3 (beta = 0.07, P = 0.02) and HIV infection (beta = À0.14, P < 0.001) were independent predictors of nonresponse. Conclusions: We demonstrated high effectiveness of 8-week GLE/PIB treatment in a non-GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non-cirrhotic patients regardless of the genotype, including GT3 HCV.

Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.

The pathogenesis of coronavirus disease 2019 (COVID-19) is complicated, and in addition to antiviral therapy and combating coagulopathy, treatment should also include inhibition of the proinflammatory cytokines overproduction. The purpose of this study is to compare the effectiveness of tocilizumab (TCZ) and dexamethasone (DEX) administered alone or in combination in patients with severe COVID-19. Patients and Methods: Patients were selected from the SARSTer database, containing 3330 individuals with COVID-19 treated between 1 March 2020 and 10 March 2021. The current study included adult patients with baseline oxygen saturation (SpO 2 ) ≤90%, requiring regular or non-invasive high-flow oxygen supplementation. Results: Among included 460 patients, 59 were treated with TCZ, 125 with TCZ and DEX, 169 with DEX, and 107 did not receive TCZ nor DEX. The groups were balanced regarding demographics, coexisting diseases, baseline SpO 2 , and comedications with remdesivir or low-molecular-weight heparin. The death rate of 6.8% was significantly lower in patients receiving TCZ alone than each arm (19.6%-23.1%), particularly in patients with interleukin-6 concentration exceeding 100pg/mL (5% vs 22.9%-51.7%, respectively). Analysis of clinical improvement demonstrated doubled, significantly higher rate after 21 and 28 days in patients treated with TCZ alone (60% and 75%, respectively) compared to DEX (27.6% and 37.9%, respectively). The need for mechanical ventilation was similar in all arms. Conclusion:In patients with severe course of COVID-19, particularly those developing cytokine storm, administration of TCZ provides a significantly better effect than DEX regarding survival, clinical improvement, and hospital discharge rate. The combination of TCZ and DEX does not improve therapy effectiveness in patients with severe COVID-19 compared to the administration of TCZ alone.