Objectives: The potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine... Show moreObjectives: The potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine the effectiveness of CP therapy in improving the disease course of COVID-19 among high-risk outpatients. Methods: A multicentre, double-blind randomized trial was conducted comparing 300 mL of CP with non-CP. Patients were >= 50 years, were symptomatic for <8 days, had confirmed RT-PCR or antigen test result for COVID-19 and had at least one risk factor for severe COVID-19. The primary endpoint was the highest score on a 5-point ordinal scale ranging from fully recovered (score = 1) or not (score = 2) on day 7, over hospital admission (score = 3), intensive care unit admission (score = 4) and death (score = 5) in the 28 days following randomization. Secondary endpoints were hospital admission, symptom duration and viral RNA excretion. Results: After the enrolment of 421 patients and the transfusion in 416 patients, recruitment was dis-continued when the countrywide vaccination uptake in those aged >50 years was 80%. Patients had a median age of 60 years, symptoms for 5 days, and 207 of 416 patients received CP therapy. During the 28 day follow-up, 28 patients were hospitalized and two died. The OR for an improved disease severity score with CP was 0.86 (95% credible interval, 0.59-1.22). The OR was 0.58 (95% CI, 0.33-1.02) for patients with <5 days of symptoms. The hazard ratio for hospital admission was 0.61 (95% CI, 0.28-1.34). No difference was found in viral RNA excretion or in the duration of symptoms. Conclusions: In patients with early COVID-19, CP therapy did not improve the 5-point disease severity score. Arvind Gharbharan, Clin Microbiol Infect 2023;29:208 (c) 2022 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Background In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide... Show moreBackground In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015.Methods In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed. We used parametric proportional hazards models with a piecewise exponential survival function to model HCV primary infection and reinfection incidence per 1000 person-years.Findings Of the 23 590 individuals without previous HCV infection, 1269 cases of HCV primary infection were documented (incidence 5.2 per 1000 person-years [95% CI 5.0-5.5]). The highest incidence was observed in men who have sex with men (MSM; 7.7 per 1000 person-years [7.3-8.2]) and was lower in people who inject drugs (PWID; 1.7 per 1000 person-years [0.7-4.1]) and other key populations (1.0 per 1000 person-years [0.8-1.2]). In MSM, incidence increased in 2007 to 14.3 per 1000 person-years and fluctuated between 8.7 and 13.0 per 1000 person-years from 2008 to 2015. In 2016, incidence declined to 6.1 cases per 1000 person-years and remained steady between 4.1 and 4.9 per 1000 person-years from 2017 to 2019. Of the 1866 individuals with a previous HCV infection, 274 reinfections were documented (incidence 26.9 per 1000 person-years [95% CI 23.9-30.3]). The highest incidence rate was observed in MSM (38.5 per 1000 person-years [33.9-43.7]) and was lower in PWID (10.9 per 1000 person-years [3.5-33.8]) and other key populations (8.9 per 1000 person-years [6.3-12.5]). In MSM, reinfection incidence fluctuated between 38.0 and 88.9 per 1000 person-years from 2006 to 2015, reaching 55.6 per 1000 person-years in 2015. In 2016, reinfection incidence declined to 41.4 per 1000 person-years, followed by further decreases to 24.4 per 1000 person-years in 2017 and 11.4 per 1000 person-years in 2019.Interpretation The sharp decline in HCV incidence in MSM with HIV shortly after restrictions on DAAs were lifted suggests a treatment-as-prevention effect. HCV incidence was already low in PWID and other groups before unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but high rate of reinfection, stressing the need for additional preventive measures. Copyright (C) 2020 Elsevier Ltd. All rights reserved. Show less
Nearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation... Show moreNearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation and co-morbidity were important exclusion criteria, and were related to toxicity. Therefore, new drugs should also be studied in these patients, to genuinely assess benefits and risk of therapy in the real world population. Show less
