CLN - Focus on Molecular Diagnostics
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As summer turns to fall, respiratory viruses are about to be in the spotlight. The clinical laboratory is essential in detecting which pathogens are circulating in the community, how those pathogens are affecting different populations, and how those patients will be tested and treated.
We spoke with Catherine Moore MBE, PhD, FRCPath, consultant clinical scientist at Public Health Wales, about what her institution does to prepare, how they handle both potential bacterial and viral infections, and how surveillance — which was disrupted by the worst of the pandemic — can play a key role in helping the community through this season.
Influenza would be number one, and then SARS-CoV2, because it’s winter, we normally also target respiratory syncytial virus (RSV), which is a common cause of bronchiolitis in children. We now have immunizations available for pregnant women for RSV, as well as for the elderly.
Clinicians can also offer a new monoclonal antibody to neonates that can help protect them from RSV for up to 6 months.
In most emergency departments, they’ll do rapid tests for influenza A and B, RSV, and SARS-CoV-2.
The severity of influenza, RSV, and COVID-19 are well known. However, the impact of other respiratory viruses has probably been underestimated and under-resourced for many years. That includes those associated with rhinovirus, also known as the common cold; parainfluenza, human metapneumovirus, and various other respiratory infections that people get all year round. In certain populations, like those who are immunosuppressed, they can be severe.
When we look at local testing in Wales, we have a range of multiplex PCR-based molecular panels that are specific for different patient groups. If it is a patient who is normally fit and well, it would be appropriate to use an influenza A and B, RSV, and SARS-CoV-2 panel. For patients who are immunosuppressed, the clinicians could suspect rhinovirus or parainfluenza.
Pre-pandemic, it was the laboratory running most of the panels. There was a little bit more expansion into emergency departments for things like influenza, but broad panels that include a lot of other respiratory infections were only just being introduced. Commercial companies were bringing out expanded panels, with ongoing studies to look at implementation in emergency departments — in particular, how they affected patient management and patient flow through hospital systems. But they weren’t really being taken up because they are quite expensive.
Since we started to come out of the pandemic, we’re now seeing expansion, not just in expert areas of microbiology, virology, and other areas of laboratory medicine, but directly into emergency departments. The world has definitely changed.
For the most part, multiplex PCR testing is still mostly for viral infections because the evidence base is more clear. We’ve been doing viral molecular testing for decades. I set up testing back in the early 2000s, and we’ve been expanding ever since. We have good evidence of utility and of the caveats that go with that testing. With bacteria, it’s only just starting to take off.
Outside of the four that we generally test for — influenza A and B, RSV and SARS-CoV-2 — we don’t really have enough evidence about other viruses or other pathogens. So, expanding the panels and looking at clinical symptoms associated with those other viruses and pathogens can only help public health.
One of the things we struggle with most as virologists and clinicians is looking after people with viral infections, particularly in the immunosuppressed population. The more that we test and the more we understand the morbidity of these infections, the more we might drive better treatment and better prevention.
Surveillance is very close to my heart. It’s one thing I have been passionate about since the early 2000s: making sure the surveillance of these infections is understood, and that we incorporate as many pathogens as possible in our sentinel surveillance schemes.
Sentinel surveillance for influenza involves extensive testing to characterize circulating viruses, helping us better understand clinical presentations and the effectiveness of current vaccines. We expanded this system by including additional pathogens. We have detailed information about patients' underlying conditions, whether they are children or adults. The symptoms they present with are clearly listed, along with their immunization status. This allows us to investigate other pathogens and viruses and examine what patients are presenting with at their general practitioners.
The pandemic disruption was significant. People were encouraged not to go to primary care. It was difficult to understand how other viruses were circulating in the community. Everybody was presenting with COVID-19 at the same time, and we weren’t always getting the information we were looking for.
We were very keen, throughout the pandemic, to bring back our sentinel surveillance and look at novel ways of collecting that information from the community — and not just about COVID-19. In particular, we wanted surveillance of influenza because we knew it would start circulating again.
It depends on the patient population and on who is delivering the test. For the big four — influenza A and B, RSV and COVID-19 — there are pathways in place, and treatment options, the laboratories know very well how to deliver high quality and appropriate testing.
Expanding outwards to rhinovirus or parainfluenza, the evidence becomes less well established. Sometimes these wider panels are being performed directly in emergency departments, but without any background or understanding of what those infections might cause, or what their treatment might be. That could lead to problems, because symptoms overlap quite a lot in some of these infections, particularly if the patients have other underlying conditions.
For those panels, clinicians are likely to engage with experts, whether that’s local infectious disease teams or microbiologists, to support management of those patients with infections that aren’t those big four.
A big concern for us is that the sequences of viruses and pathogens change all the time. RNA pathogens are particularly prone to mutation. As a result, we don’t always know if the test being used is still able to detect the target if it has mutated.
We experienced that problem a lot with SARS-CoV-2, and it is also relevant with influenza, RSV, and parainfluenza. The test might be working well for one particular type of virus, but next year it might not work so well. I believe we could be missing a lot of cases.
That’s why surveillance is important, but also the engagement of experts who perform ongoing genomic analysis of the pathogens. The laboratory must make sure that the test is actually testing for what it says it does, because it doesn't take much for a test to stop working. I think engagement between experts and commercial companies developing these tests is essential.