Influenza virus detection directly from clinical samples
Research type
Research Study
Full title
A comparison of clinical sample collection methods to detect Influenza virus and other respiratory pathogens using whole genome sequencing
IRAS ID
269573
Contact name
Derrick Crook
Contact email
Sponsor organisation
University of Oxford/Clinical Trials and Research Governance
Duration of Study in the UK
0 years, 11 months, 30 days
Research summary
Summary of Research
Influenza virus infection causes an estimated 650,000 deaths globally each year with risk for infection higher among certain groups, including older adults, infants and young children, pregnant women and those with underlying lung disease. Influenza virus infection is listed by the World Health Organisation (WHO) as one of the ‘ten threats to global health’ in 2019. Current diagnosis of Influenza virus relies on a patient providing throat swab or nasopharyngeal aspirate that is placed in a solution to preserve the virus. The diagnostic laboratory then tests this by looking for small parts of the genetic material of the virus (a method called PCR). Diagnosis of other respiratory viruses requires different expensive tests. New technology allows all the genetic material in a sample to be extracted and tested using a method called whole genome sequencing, allowing us to identify both Influenza and other viruses using one test. The information that the test provides can also tell us about both resistance to anti-viral drugs and whether viruses are spreading between people.We will recruit patients who attend the Emergency Department at the John Radcliffe hospital who have respiratory symptoms. Participants will be asked to provide an oral fluid sample in addition to the normal clinical sample that is taken and optionally an extra throat swab. We ask for information on flu vaccinations and duration of symptoms.
Our primary goal is to investigate whether a new sample, an oral fluid sample, is suitable to diagnose influenza virus by comparing the results from sequencing with the standard laboratory results. Our secondary goal is determine whether the oral fluid sample is suitable to identify other respiratory viruses using one test and whether we can use the genetic information to confirm both resistance to anti-viral agents and whether viruses are spreading between people.
Summary of Results
Diagnosis of influenza (“flu”), which is a virus that causes respiratory (chest) infections, has traditionally relied on a patient providing a nose and/or throat swab that is collected in a special fluid to preserve the virus while it is transported to the laboratory. The hospital laboratory then tests this fluid by looking for small parts of the genetic material that make up the virus (a method called PCR). Diagnosis of other respiratory viruses then requires several different, and sometimes expensive, tests. New technology allows all the genetic material in a sample to be tested using a method called whole genome sequencing, enabling us to identify both flu and other viruses using the same test. The information that the new test provides can also tell us other information that is important for providing clinical care, such as whether anti-viral drugs will be effective as treatment, and detecting whether viruses are spreading between people.
The primary goal of our original study was to investigate whether a new sample, a saliva sample, is suitable to diagnose flu by comparing the results from sequencing with the standard laboratory tests and results, as described above. Our secondary goal was to determine whether the saliva sample is suitable to identify all respiratory viruses using one test, and to investigate the ways we can use this genetic information about the virus to identify whether anti-viral treatments will work and to investigate how viruses are spreading in the community. This might also provide information that helps us to understand the extent to which flu infection can be prevented by vaccination. In the long term, results of this study will contribute to better and quicker diagnosis of chest infections like flu, and therefore help the correct treatment choices to be made promptly. It will also provide insights into the spread of flu, and may help to inform improvements in vaccines so that we can protect more people from flu infections.
We stopped flu study recruitment in March 2020 (3 months after study start) because of the onset of the SARS-CoV-2 (Covid) pandemic. The seasonal pattern of respiratory virus infections, including flu, was also completely changed as a result of Covid and changing public health policy (because many people were in lockdown for long periods of time), with very few flu-positive cases noted locally or nationally in 2020-2022, which made our original recruitment targets unfeasible.
As a result we changed the study design to focus on diagnosing Covid infections, mostly to rapidly support the development of novel Covid tests, including lateral flow tests for national roll-out, and the development of a new test method using a very powerful microscope that can "see” viruses labelled with fluorescent markers directly in clinical samples. This test can identify different types of common virus that cause chest infections, including Covid and flu, and is being expanded to identify different types of germ that cause disease, such as bacteria.
Patient cohort (pre-pandemic):
• Flu study Dec 2019-early 2020: 94 screened, 36 tested, 3 flu positive (1 flu A, 2 flu B)
Patient cohort (during pandemic):
Symptomatic cohort: 94 participants
Asymptomatic cohort: 343 (738 samples, of which 703 evaluable [339 saliva and 364 throat swabs])REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
19/NW/0730
Date of REC Opinion
11 Dec 2019
REC opinion
Further Information Favourable Opinion