Claire Green reports from the Westminster Health Forum conference on diagnostics and pathology
The Westminster Health Forum conference, Next steps for diagnostics and pathology—innovation, collaboration, standards, and the response to the COVID-19 pandemic, was held online on 16 September 2020.
Professor Sir Mark Caulfield, Chief Scientist at Genomics England and Professor of Clinical Pharmacology at the William Harvey Research Institute, Queen Mary University of London, outlined some of the ways in which innovation, integration, shared resources, and new technologies have helped to tackle the COVID-19 pandemic. Innovations and achievements during the pandemic have included:
- the rapid creation of the Nightingale hospitals
- development of master data sets
- NHS data sharing, both nationally and globally
- COVID-19 treatment trials started early in the pandemic
- a world-leading viral surveillance programme, which sequenced 45,000 viruses (over 50% of the viruses sequenced worldwide) and identified new variants
- a national programme to understand why some people are more severely affected by COVID-19.
Technological innovations by UK life‑sciences companies and academia include the development of protocols to enable very high-throughput viral genome sequencing (which makes it possible to run a surveillance system for new viral infections),1 a new assay that can measure the virus in saliva or swabs at a rate of 15,000 tests per day using a desktop device,2 and many new antibody tests, some of which are analogous to pregnancy tests. However, we need to be aware that all of these tests yield some false-positive and false-negative results.
Genomic testing has been used to diagnose the presence and evolution of the virus.3 A recent study identified host cell factors critical for infection with the virus, which may form the basis of preventive measures and treatments in future.4 Genomics can be also used to predict which patients are likely to be more susceptible to serious illness following COVID-19 infection.5
… innovation, integration, shared resources, and new technologies have helped to tackle the COVID-19 pandemic.
These achievements illustrate the potential for collaborations between UK life-sciences companies, industry, and academia to respond with new insights, diagnostics, and therapies.
Professor Jo Martin, Professor of Pathology, Queen Mary University of London, Director, Academic Health Sciences, Barts Health NHS Trust, and President, Royal College of Pathologists, said that testing capabilities for COVID-19 have been built up from nothing to have the ability to detect the presence of, determine the antibody response to, and examine the genetic sequence of the virus. To achieve this, there has been a lot of input from different disciplines, including veterinary pathologists, immunologists, virologists, and microbiologists.
… testing capabilities for COVID-19 …have the ability to detect the presence of, determine the antibody response to, and examine the genetic sequence of the virus.
Having an overall strategy around how testing should be used is important. Professor Martin set out the principles for testing (see Box 1); testing should be matched to purpose and pathways, whether it detects the presence of the virus, the immune response to it (antibodies and T-cells), or its genetic sequence. Different tests are useful for individual patients, groups of patients, populations, or viruses. For example, a simple test may not be as accurate as a laboratory test, but may be useful to gather data about a population; however, testing patients prior to admission to hospital needs high levels of accuracy to avoid introducing COVID-19 to a ward or staff group.
Box 1: Principles of testing
- The right test must be a carried out for the right purpose, at the right time, and with the correct result—the result includes the appropriate clinical interpretation
- Testing should be carried out to accredited quality standards by skilled, trained professionals
- Problems in testing lead to problems in care
- Data connectivity and links to health records are key
- People should be clear about what they are being tested for and the test limitations and, if part of a research programme, can opt out
- Information should be clear and understandable.
Clinical interpretation is important because a lot of the tests being carried out at the moment are at the margin of a result—neither positive or negative. Some results may be very weakly positive, and clinical input is required to ascertain what that means. In future, home-use tests may be developed, validated, and regulated, which may be appropriate in some circumstances, for example for people with non‑specific symptoms that may indicate COVID-19, such as a headache or cold.
Connectivity is key
Isolated laboratories not linked to the health service are suboptimal. There is good infrastructure for electronic healthcare in most places, and laboratories have information‑management systems where pathology data is kept. These systems need to be linked together. Astonishingly, during the pandemic, 99.9% of laboratories were linked up across England within 3–4 weeks. This would have taken years under normal circumstances, and is an unsung triumph of the information technology (IT) infrastructure of the NHS and laboratories. Results can now be sent to Public Health England (PHE) and patients’ GPs. However, there are still some problems with the connectivity of some of the mega laboratories.
Digital pathology is helpful because it enables professionals to work from home and to share images in a much more efficient and flexible way than was previously possible. Digital pathology also enables artificial intelligence (AI) development, so we need to make sure that AI planning is matched by the underlying infrastructure.
Clinical interpretation is important because a lot of the tests being carried out at the moment are at the margin of a result—neither positive or negative.
Innovation
In terms of innovation, ‘epic’ work has been done in rolling out testing. This process would normally take a long time, but during the early phases of the pandemic, implementation was rapid and nimble. Laboratories fed back about any issues to PHE, meaning that innovation was iterative.
Rapid upskilling and secondment into different jobs has been a feature of the pandemic, but this needs to be sustainable. Learning and development seminars have been very useful, but staff being released to undertake activities related to continuing professional development is a real problem.
Professor Martin reminded the audience that, with winter coming, innovation was needed in terms of multiplex respiratory virus testing—combining COVID-19 testing with influenza and parainfluenza viruses and other winter pathogens. In addition, COVID-19 affects the gut,6 so distinguishing between this and other gut bugs will require further innovations in testing. She added that innovation needed to continue at pace, and not be slowed by external conditions.
… with winter coming, innovation was needed in terms of multiplex respiratory virus testing—combining COVID-19 testing with … other winter pathogens.
Testing capacity
Every single laboratory in the country has had to change the type of testing implemented several times because consumables and technology have been in short supply. They have also had to switch—and sometimes shut down—platforms because consumables have been diverted to one of the mega labs. Globally, there was a massive shortage of consumables at the beginning of the pandemic, and not much could have been done about it. However, in general, laboratories have coped well.
Forethought about workforce and investment in NHS laboratories would have been helpful, especially to create a more sustainable structure. Workload for normal testing dropped during the pandemic, and this will have to increase again. Around a quarter of histopathology laboratories were understaffed even before the pandemic.
Testing is vital to unlock some of the pathways for diagnostics. If people can be tested rapidly enough, they can pass through the health services more quickly. Ideally, people would not have to wait 48 hours for a test result—for example, if 60–90-minute tests were used.
Doris-Ann Williams MBE, Chief Executive, British In Vitro Diagnostics Association, talked about the importance of communication in the response to COVID-19, and key learnings for the future. She said that there was little direct contact with the Government until mid-March 2020, and that many smaller companies had felt ignored. There was a real desire from the sector to support the pandemic response through diagnostic testing. At the end of March, a meeting took place with Matt Hancock, Secretary of State for Health and Social Care, about the need to rapidly increase the number of tests per day. It was a huge learning curve for everyone. Weekly webinars with Government were really helpful, as were existing relationships.
Coronavirus test manufacturing had to rapidly scale up from scratch. There was lots of stress, and it required long days, incredible professionalism, and complete dedication. It was disappointing that, although companies were able to rapidly develop serology tests for antibodies, coronavirus antibodies do not appear to be long lasting,7 and T-cell response may be a more important indicator of protective immunity against the virus.8,9 The antibody test has been valuable for surveillance, especially for NHS and care home staff, but is not the silver bullet hoped for at the end of April 2020.
There was a real desire from the sector to support the pandemic response through diagnostic testing.
Tests always improve as they are used: a test is launched and then a new and better one is developed. That’s normal for this sector and that is still happening now, but at speed. New tests are now being brought out, suitable for different situations and different people. Multi‑testing is also being developed by some companies, which will enable differentiation between flu, COVID-19, and other respiratory infections so that patients can be rapidly triaged to ensure that infected people don’t go into clean areas of hospitals.
One fantastic idea was to crowd source for challenges. This was supported by NHS Horizons, and helped to identify new technologies. Monthly webinars were held, and over 1000 people worldwide joined and contributed ideas and suggestions. This enabled networking and led to companies forming consortia to support each other. Frequent one-to-one calls with Ministers, Member of Parliament briefings, and facilitation of visits to member company sites have been important, and this has built a solid base of contacts that will help with future engagement beyond COVID-19.
There is now higher awareness than ever before of the role of diagnostic testing in providing information for use in making healthcare decisions. Between 70% and 80% of all information used in healthcare decision making comes from diagnostics.10 During the pandemic, there was a focus on trying to educate journalists in the correct use of terminology around testing, and this has been a bit of a losing battle, but it was important to get clear information out to help people understand the issues around testing.
The antibody test has been valuable for surveillance, especially for NHS and care home staff, but is not the silver bullet hoped for at the end of April 2020.
Testing in the future
As the industry continues to work hard on large-scale COVID-19 testing, it is critical that the NHS gets back to testing and treating other patients, such as those with cancer.
In terms of innovation, near-patient testing—either in the home or in community settings—is an exciting development area for diagnostics, and we need to have the confidence to take it forward. For example, testing frail, elderly individuals to avoid unnecessary hospitalisations, and use of a new community test for pre-eclampsia in pregnancy, may become accepted practice moving forward. In addition, the Genomic Laboratory Hubs that were set up for cancer and rare inherited diseases are now doing work on COVID-19, and are likely to do more work on respiratory illnesses in future.
This conference report was prepared by Specialised Medicine and the speakers have not had the opportunity to make corrections.
References
- COVID-19 Genomics UK Consortium. COVID-19 genomics UK consortium. www.cogconsortium.uk/ (accessed 27 January 2020).
- DHSC. Press release: roll-out of 2 new rapid coronavirus tests ahead of winter. www.gov.uk/government/news/roll-out-of-2-new-rapid-coronavirus-tests-ahead-of-winter (accessed 27 January 2020).
- Rahimi A, Mirzazadeh A, Tavakolpour S. Genetics and genomics of SARS-CoV-2: a review of the literature with the special focus on genetic diversity and SARS-CoV-2 genomic detection. Genomics 2020; 113 (2021): 1221–1232.
- Hoffman M, Kleine-Weber H, Schroeder S et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271–280.
- Pairo-Castineira E, Clohisey S, Klaric L et al. Genetic mechanisms of critical illness in Covid-19. Nature 2020; Epub ahead of print. doi.org/10.1038/s41586-020-03065-y
- Villapol S. Gastrointestinal symptoms associated with COVID-19: impact on the gut microbiome. Transl Res 2020; 226: 57–69.
- Figueiredo-Campos P, Blankenhaus B, Mota C et al. Seroprevalence of anti-SARS-CoV-2 antibodies in COVID-19 patients and healthy volunteers up to 6 months post disease onset. Eur J Immunol 2020; 50: 2025–2040.
- Zuo J, Dowell A, Pearce H et al. Robust SARS‑CoV-2-specific T-cell immunity is maintained at 6 months following primary infection. bioRxiv 2020; Epub ahead of print. doi.org/10.1101/2020.11.01.362319
- Altmann D, Boyton R. SARS-CoV-2 T cell immunity: specificity, function, durability, and role in protection. Sci Immunol 2020; Epub ahead of print. doi.org/10.1126/sciimmunol.abd6160
- DHSC. Report of the review of NHS pathology services in England. London: DHSC, 2006. Available at: www.networks.nhs.uk/nhs-networks/peninsula-pathology-network/documents/CarterReviewPathologyReport.pdf