FASTER Study [COVID-19]
Research type
Research Study
Full title
Facilitating A SARS CoV-2 TEst for Rapid triage (FASTER)
IRAS ID
282147
Contact name
Andrea Collins
Contact email
Sponsor organisation
Liverpool School of Tropical Medicine
ISRCTN Number
ISRCTN89159899
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
In December 2019 a cluster of cases of pneumonia from a novel coronavirus called SARS-CoV-2 (COVID-19), was reported in Wuhan, China (1,2). This outbreak has spread rapidly, with over 160,000 reported Coronavirus disease (COVID-19) cases and 6,600 deaths as of March 16th, 2020 (3). The World Health Organisation (WHO) declared on the 12th of March the COVID-19 outbreak a pandemic (4). Currently, Europe has become the epicentre of the pandemic and in the UK, cases are increasing. Due to the rise of the number of samples to diagnose, tests are taking longer than expected. Among the foremost priorities to facilitate public health interventions is a reliable laboratory diagnosis. Prompt case confirmation is necessary to ensure rapid and effective contact tracing, implementation of infection prevention and control measures according to WHO recommendations, and collection of relevant epidemiological and clinical information. The ultimate diagnosis of COVID-19 is performed by laboratory testing as the clinical features are non-disease specific. Diagnostic testing for COVID-19 is currently undertaken using real-time reverse transcriptase PCR (RT-PCR) to detect the viral ribonucleic acid (RNA). These assays are sensitive but require sending the samples to reference laboratories and thus results are obtained with a delay. In the UK, results are reported with a delay of 2-4 days (5) impeding the correct triage of patients, correct isolation measures and therefore putting the community and healthcare workers at risk.\nA fast and reliable diagnostic assay that could be used at the point-of-need (PON) is yet to be developed. We have been working closely with our commercial partners in 2020 on the development of highly sensitive PON tests to facilitate diagnosis at the point of need and to reduce the consequences of diagnostic delay.\n\nWe will use dual antigen and antibody test prototype lateral flow tests and ELISA that are ready for preliminary evaluation, and subsequently use the lateral flow tests on-site to evaluate the test at the point of need. Left over and anonymised samples will be used to evaluate other diagnostic tests if appropriate.\n \nAdditionally, it is currently unknown why some patients develop severe COVID-19, while others have mild symptoms by the same SARS-CoV-2 infection. Although general predisposing factors, such as hypertension, kidney disease and diabetes are well established, immunopathogenesis data of severe infections involve hyper-inflammatory responses and cytokine storm but are less characterised. Colonisation of the nasopharynx results in micro-aspiration of pneumococci and promotes activation of alveolar macrophages with an inflammatory phenotype (6). Further activation by COVID-19 may lead to overwhelming inflammatory responses. \nPrevious studies have demonstrated that the presence of virus can increase pneumococcal colonisation facilitated by a pro-inflammatory response resulting in a secondary infection and increased disease severity. It is important therefore to investigate the relationship between COVID-19, S. pneumonia colonisation and disease severity. \n\nThe information from our study will add significantly to the understanding of COVID-19 diagnostics and control and will improve the evidence-base for the protection of patients, healthcare workers and the community from outbreaks of COVID-19. The acquired knowledge of this project will also consult current pneumococcal vaccination strategies that could halt cases of severe COVID-19 infection or prevent disease exaggerations due to a secondary pneumococcal infection in the seniors.\n\nThis will be an observational study taking samples and collecting data from patients admitted to Liverpool University Hospital NHS Foundation Trust (LUHFT) with suspected COVID-19. \n\nParticipants and enrolment\nAll individuals fulfilling the inclusion criteria will be invited to take part in the study. Participation will be voluntary and there will be no payment. It is expected patients will appreciate the potential benefits of the study and be willing to participate. \n\nMembers of the research team will attend the clinical areas to invite eligible individuals to enrol. Verbal and written information, including a patient information leaflet (PIL) will be provided to eligible candidates. \nDue to the minimal burden of the study and the emergency condition of the patient, witnessed verbal consent will be sought in order to commence taking samples and data collection. Verbal consent will be witnessed by a member of the clinical team and documented for evidence. A copy of the participant information leaflet will be given to the participant for their records.\n\nIf a participant loses capacity during the study due to a deterioration in their condition, samples and data will continue to be collected. These participants have previously given witnessed verbal consent and participation is considered minimally intrusive with data collection and minimally invasive samples only. Due to the nature of the disease, it is considered that a large number of participants may require ventilation thereby loosing capacity. In order to gain scientific merit from such studies, we need to validate the use of the PON tests with a variety of patients experiencing varied severity of disease. Removing these participants would negatively affect the validation of the test. In normal circumstances we would ask for a nominated consultee on behalf of the participant however family members are prohibited from entering the hospital to reduce the spread of the pandemic. In this instance, we would continue to take samples and collect data unless a treating clinician though t that this was inappropriate. All data and samples will be anonymised.\n\nThe research team (nurses/doctors) will screen patients that are admitted to LUHFT with respiratory symptoms and symptoms typical of COVID-19. These patients will be given a participation information leaflet (PIL) and verbal information. They will be given adequate time to decide if they wish to participate in the study. If they are happy to participate in the study, they will be asked to give verbal consent that will be witnessed and documented by a member of the clinical team. The baseline samples will be taken on the same day as the verbal consent.\n\nParticipants will be able to take part in multiple research studies relating to COVID-19 in order to increase the knowledge of pandemics. We are collecting samples at different timepoints deliberately so there is minimal daily burden on patients for samples.\n\nInclusion criteria\n\n•\tAdults 18 years old \n•\tPresenting with COVID-19 symptoms \no\tfever ≥37.80C +/-\no\tshortness of breath +/-\no\tnew/ persistent cough\nOR\no\tClinical or radiological evidence of pneumonia\n•\tFluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement\n•\tCapacity to give informed verbal consent \nExclusion criteria\n•\tChildren under 18 years old\n•\tNo symptoms of COVID-19\n•\tLack of capacity and unable to perform verbal consent\n\nParticipants will be free to withdraw from the study at any point without giving any reason. Data and samples taken up to the point of withdrawal will be used, however no further samples or data will be collected. \n\nThe enrolment questionnaire will collect demographic and comorbidity data as well as baseline symptoms. Each subsequent sampling will include a very brief symptom questionnaire. All data will be entered onto LSTM’s protected servers.\n\nStudy period\nThe study period will start as soon as possible after ethical approval is granted and will continue for a period of up to 12 months. \n\nSample size\nThe proportion of patients with symptomatic COVID-19 who will attend the LUHFT is not known, thus sample size calculations are challenging. Current testing (early March 2020) indicates ~20% of suspects are COVID-19 positive. The R0 is expected to be between 2 and 3 but the number of patients who will be admitted, as well as the effectiveness of the recruitment process is not known. We expect to recruit at least 400 participants. Enrolling 400 participants would allow a precision of +/- 0.03 with 95% of confidence if the prevalence of positives was around 10%. If there was a strong desire to participate in the study, the enrolled number could be increased, pending additional funding.
REC name
South Central - Oxford C Research Ethics Committee
REC reference
20/SC/0169
Date of REC Opinion
27 Mar 2020
REC opinion
Favourable Opinion