ISARIC 4C (Coronavirus Clinical Characterisation Consortium)

We are a UK-wide consortium of doctors and scientists committed to answering urgent questions about COVID-19 quickly, openly, and for the benefit of all.

how long are people infectious, and what body fluids are infectious?
what puts people at higher risk of severe illness?
what is the best way to diagnose the disease?
who should we treat early with drugs, and which drugs cause harm?
does the immune system in some patients do more harm than good?
what other infections(such as pneumonia or flu) happen at the same time?

The UK needs a coordinated response to answer these questions as quickly as possible. Over the last 8 years we have been preparing for such a major outbreak worldwide International Severe Acute Respiratory Infection Consortium Clinical Characterisation Protocol; our team deployed immediately and has been collecting data and samples since the first cases were reported in the UK.

Funding

ISARIC 4C is funded by a grant from UKRI (MRC) with a total value of £5.9M to JK Baillie (PI), University of Edinburgh; MG Semple, University of Liverpool; and P Openshaw, Imperial College London (co-leads). Full list of investigators and specific deliverables.

Plan

We are funded to obtain serial samples from 300 cases and single samples for a further 1000. A full list of samples can be found in the UK clinical characterisation protocol. This is a generic, sleeping protocol that is designed to give fast responses with global harmonisation during outbreaks.

We will share samples to get answers as fast as possible. We will not end this outbreak sitting on a biobank; our intention is to use every drop of every sample, now, to have the biggest possible impact on the COVID-19 crisis. Any investigators with the ability to contribute can access our data and samples. The ISARIC-4C study will provide a foundation for other studies, such as clinical trials of new treatments, to help better understand the best way to use interventions.

Landscape of urgent UK-wide research in COVID-19.

ISARIC 4C is one the UK-wide NIHR Urgent Public Health Priority studies for hospitalised patients with COVID-19:

Any hospitalised patient

ISARIC 4C

ISARIC Clinical Characterisation Protocol (CCP) Tier 0 (CO-CIN)

Data collection, no consent

COVID19 Clinical Information Network (DHSC-funded). Near real-time analysis and reporting of the clinical characteristics of patients admitted to hospital with SARS-CoV-2 infection, to inform the research and public health responses. To achieve this we need clincal research nurses and administrators to gather data from clinical notes and enter it into a simple online database.
ISARIC Clinical Characterisation Protocol (CCP) Tiers 1/2 (4C)

Sample collection, consent needed

COVID19 Clinical Characterisation Consortium (MRC-funded). Obtaining research samples. Either one sample set at recruitment, or 4 sample sets on Day 1, 3, and 9 and (if possible) another set 28 days after discharge. Aims to understand transmission, pathogenesis, and prognosis. To achieve this we need PPE-trained research nurses to obtain consent, and samples of pathogen shedding sites and blood.

RECOVERY TRIAL

Adaptive platform drug trial, consent needed

Randomised Evaluation of COVID-19 Therapy (MRC/DHSC-funded). Trial of widely available, high-priority interventions, among confirmed COVID19 cases requiring hospital admission, to determine effect on death or requirement for invasive ventilation. Interventions will be added and removed over time as needed. Given the unprecedented impact COVID 19 will have on the health of the population, even small clinical benefits may be of significant benefit. Designed to give individual patients the best chance of getting an effective therapy. To do this we need GCP-trained research nurses to support front-line clinical staff recruiting patients.

RECOVERY-RS trial

Adaptive platform trial of supportive care interventions, consent waived

RECOVERY-RS is a multi-centre, pragmatic clinical trial evaluating the use of CPAP and / or high flow nasal oxygenation to prevent intubation and reduce mortality. Uncertainty about the effectiveness of CPAP / HFNO in COVID-19 have led to conflicting guidance on the use of these interventions. Recruits patients with acute respiratory impairment (FiO2 >0.4 and SpO2 < 94%). Sites may choose to enrol in one or both arms of the trial (CPAP versus standard care, HFNO versus standard care or CPAP versus HFNO versus standard care). Sites are encouraged to contact the co-ordinating centre at RECOVERY-RS@warwick.ac.uk to log their interest in participation.

Patients in Critical Care

GenOMICC

Genetic study, consent needed

Genetics Of Mortality In Critical Care (MRC/DHSC/FEAT/ICS/Wellcome-funded). UK-wide ICU study to identify variants underlying genetic susceptibility to critical illness with coronavirus, which may help identify new targets for treatment and mechanisms of disease. This study was funded in 2014 and was recruiting across the UK before the pandemic hit.

REMAP-CAP

Bayesian adaptive platform trial, consent needed

A Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia. This is a global platform trial in critical care with multiple arms and domains to test a variety of therapeutic interventions in critically-ill patients.