The role of antiviral treatment in COVID-19 hospitalized patients remains controversial. In this study, we analyzed nasopharyngeal viral load and the clinical score of patients (as measured by the National Early Warning Score 2 (NEWS-2)) in the DisCoVeRy trial, where 664 patients were randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to model the evolution of viral dynamics and its potential impact on clinical evolution, and to model the impact of effective antiviral treatment on clinical evolution.
Simulations predicted that antiviral activity greater than 99% could reduce the time to clinical improvement by 2 days in patients with high viral loads, regardless of the NEWS2 score on admission. While no clinically substantial effect was predicted in patients with low viral loads, these results suggest that highly potent antivirals could accelerate clinical improvement in hospitalized patients with high viral loads.
This study provides new insights into the potential role of antiviral treatment in hospitalized COVID-19 patients.

Authors:
Néant N, Lingas G, Gaymard A, Belhadi D, Hites M, Staub T, Greil R, Paiva JA, Poissy J, Peiffer-Smadja N, Costagliola D, Yazdanpanah Y, Bouscambert-Duchamp M, Gagneux-Brunon A, Ader F, Mentré F, Wallet F, Burdet C, Guedj J; DisCoVeRy study group. Association between SARS-CoV-2 viral kinetics and clinical score evolution in hospitalized patients. CPT Pharmacometrics Syst Pharmacol. 2023 Sep 20. doi: 10.1002/psp4.13051. Epub ahead of print. PMID: 37728045.

Link:
http://doi.org/10.1002/psp4.13051

Several trial consortia, including EU RESPONSE, have investigated JAK inhibitors (such as baricitinib, ruxolitinib, and tofacitinib) for the treatment in patients hospitalized with COVID-19.
However, these trials showed conflicting results, especially regarding specific subgroup of patients such as patients with co-morbidities. As part of EU RESPONSE’s effort to generate high-quality evidence for COVID-19 treatments, we have initiated a systematic review and individual patient data meta-analysis (IPDMA) of all trials that evaluated JAK inhibitors in hospitalized COVID-19 patients. This will provide clinical guidance for patients worldwide that are still in the need of COVID-19 treatment in hospitals and for upcoming pandemics. We set up a project webpage to document progress and share updates: www.jakinhibitoripdma.org.

Standard aggregate data meta-analyses, i.e. analyses that simply pool results from publications, often face challenges of poor and selective reporting in primary studies and of assessing treatment effects across subgroups of patients (such as patients with specific co-morbidities). In an IPDMA, instead, the original research data are sought directly from the researchers responsible for each study. This allows to apply the same definitions of variables across all included trials, obtain study results that had not been provided by the trial publication, assess subgroup effects, and consistently adjust for baseline differences across trials. No IPDMA has been conducted to assess the effect of JAK inhibitors in COVID-19 patients yet.

Our main objectives are:
i) To summarize the overall benefit and harm including all available evidence, including data from registered but unpublished eligible trials
ii) To investigate where treatment effects differ between pre-specified subgroups, focusing on severity of disease, COVID-19 vaccination status, comorbidity (incl. immunosuppression), concomitant COVID-19 treatment, and age
iii) To evaluate the safety profile, focusing on cardiac, cardiovascular, and thromboembolic events, and secondary infectionsThe study protocol is registered on PROSPERO.

Ensuring quality control in a COVID-19 clinical trial during the pandemic: The experience of the Inserm C20–15 DisCoVeRy study

The study Sponsor is responsible for ensuring participants’ safety and reliability of the data collected, in particular through the monitoring carried out in the investigating centers. This article presents the experience of quality control assurance in the context of the SARS-Cov2 pandemic and its multiple associated constraints.

link to the article: https://authors.elsevier.com/a/1hFYl5WqQg%7ETCq

Management of pharmacovigilance during the COVID-19 pandemic crisis by the safety department of an academic sponsor: Lessons learnt and challenges from the EU DisCoVeRy clinical trial

During a pandemic crisis, sponsors should educate and train investigators about the importance of the pharmacovigilance issues.
•The assessment of the safety profile of the investigational medicinal drug is crucial in a clinical trial related to a health crisis, but needs to be adapted.
•In a pandemic crisis: the right balance must be found between collecting a lot of data and taking into account the investigators’ lack of time to provide these data.
•The added value of this work is that the management of safety during a clinical trial in the event of a pandemic needs to be simplified, pragmatic and prioritized to avoid increasing the workload of study staff and site investigators

link to the article: https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.1072

EU-RESPONSE first face-to-face consortium meeting was succesfully held in Oslo on 11-12 May 2023, in presence of the chair of EU-RESPONSE Scientific and Ethics Advisory Board and other invited external experts. Around 60 people attended in person to discuss the project progress, acheivements and next steps.

DisCoVery publishes an article on association between SARS-CoV-2 viral kinetics and clinical score evolution in hospitalized patients

11 October 2023
The role of antiviral treatment in COVID-19 hospitalized patients remains controversial. In this study, we analyzed nasopharyngeal viral load and the clinical score of patients (as measured by the National Early Warning Score 2 (NEWS-2)) in the DisCoVeRy trial, where 664 patients were randomized to either standard of care (SoC) or SoC + remdesivir. We [...]
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