Time of administration of rabies immunoglobulins and adequacy of antibody response upon post-exposure prophylaxis: a descriptive retrospective study in Belgium.

: Data on rabies post-exposure prophylaxis (PEP) and the use of human rabies immunoglobulins (HRIG) in Belgium are scarce. The main objective of this study was to evaluate the timely administration of HRIG after rabies exposure. The secondary objective was to evaluate the adequate antibody response following PEP.&nbsp;: We reviewed all medical records from July 2017 to June 2018 of patients seeking care at, or referred to, the Institute of Tropical Medicine and the University Hospital, Antwerp for the administration of human rabies immunoglobulins following potential rabies exposure abroad or in Belgium. A timely response was defined as starting HRIG with a delay of ≤48 h and rabies vaccination in the first 7 days after exposure. Adequate antibody response was defined as a titer of &gt;5.0 IU/mL in case of bat-related exposure and &gt;3.0 IU/mL in case of exposure to other animals. Titers were measured 10 days after the last PEP vaccine dose, using the rapid fluorescent focus inhibition test (RFFIT).&nbsp;: Of the 92 cases treated with HRIG, 75 were evaluated. The majority of injuries were acquired in Asia (n = 26,34%) and in Western Europe (n = 18, 24%), of which 17 in Belgium. The five most frequently recorded countries overseas were Indonesia (n = 13), Thailand (n = 7), Morocco (n = 4), Peru (n = 3) and Costa Rica (n = 3). Administration of immunoglobulins was related to injuries by dogs (36%), monkeys (25%) or bats (22%). A timely response was observed in 16 (21,33%) and in 55 (73,33%) of subjects receiving HRIG (≤48 h) or rabies vaccine (&lt;7days) respectively. The mean time between exposure and the first administered dose of rabies vaccine and HRIG was 7.7 and 8.7 days, respectively. The mean delay for HRIG administration was 9.6 days and 6 days for abroad and inland risks, respectively. In 15 of 16 (94%) bat-related cases the antibody titer after full PEP was &gt;5.0 IU/ml. In 38 of 47 (81%) cases related to other animals the RFFIT titer was &gt;3.0 IU/ml. All low-responders received additional rabies injections.&nbsp;: This study showed a substantial time delay between the animal-related risk and the administration of HRIG, in particular when the injury occurred abroad. More targeted communication about the risks of rabies and preventable measures may reduce this delay. Furthermore, the antibody response was inadequate in some cases following full PEP administration according to the Belgian&nbsp;recommendation.</p

Unravelling data for rapid evidence-based response to COVID-19: a summary of the unCoVer protocol

Introduction unCoVer—Unravelling data for rapid evidence-based response to COVID-19—is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving&nbsp;pandemic. Methods and analysis From the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients’ baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often&nbsp;excluded. Ethics and dissemination After strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer’s activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference&nbsp;communications.</p

Unravelling data for rapid evidence-based response to COVID-19: a summary of the unCoVer protocol.

INTRODUCTION: unCoVer-Unravelling data for rapid evidence-based response to COVID-19-is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving&nbsp;pandemic. METHODS AND ANALYSIS: From the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients’ baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often&nbsp;excluded. ETHICS AND DISSEMINATION: After strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer&#8217;s activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference&nbsp;communications.</p

Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants

Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across&nbsp;various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use&nbsp;of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19&nbsp;hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group)&nbsp;were compared with patients treated with supportive care only (no-HCQ group) using a competing risks&nbsp;proportional hazards regression with discharge alive as competing risk, adjusted for demographic and&nbsp;clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May&nbsp;2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the&nbsp;multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard&nbsp;ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617–0.758]. Compared with the no-HCQ group,&nbsp;mortality in the HCQ group was reduced both in patients diagnosed ≤5 days ( n = 3975) and &gt; 5 days ( n =&nbsp;3487) after symptom onset [aHR = 0.701 (95% CI 0.617–0.796) and aHR = 0.647 (95% CI 0.525–0.797),&nbsp;respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently&nbsp;associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later&nbsp;after symptom&nbsp;onset.</p