AP Podcast Episode 150

We have to control which lineages are circulating, in order that if there is a sudden rise in a selected emergent pressure, or a rise in severity is famous, that we all know what is going on on and we all know early.

[Music] Welcome to the Australian Prescriber Podcast. Australian Prescriber, impartial, peer-reviewed, and free.

COVID testing used to dominate our lives. It was one of the crucial seen cornerstones of an intensive take a look at, hint, and isolate public well being technique in 2020 and 2021 particularly. Maybe hardly ever, if by no means earlier than, had infectious illnesses testing been so outstanding in our society. Nevertheless, since that point initially of the COVID pandemic, our understanding of COVID testing methods has grow to be extra refined. However the place can we stand now by way of observe, and what can we be taught from it? I am David Liew, your host for as we speak, and we’re again with the Australian Prescriber Podcast. I am very glad to welcome Ella Meumann to the podcast as we speak. She’s an infectious illnesses doctor, and he or she’s written an article in Australian Prescriber on Testing for COVID-19: the 2023 Replace. Ella, thanks for becoming a member of us.

Thanks for having me on the present.

So Ella, earlier than we actually get into this, let’s simply take a step again and ask, what’s taking place with COVID now, particularly concerning variants of concern?

To recap, for the primary couple of years of the pandemic, the case numbers in Australia had been low, till our borders opened in direction of the tip of 2021, at across the time of the Omicron wave. And since that point we have had widespread neighborhood transmission in Australia, with a number of waves arising from the assorted Omicron sublineages. This yr we did have a rise in instances in Might, so early winter, not fairly winter, however a gradual decline since then. For the reason that begin of the pandemic, genomic surveillance for SARS-CoV-2 has been carried out via AusTrakka and the Communicable Ailments Genomics Community, a nationwide public well being laboratory group, and so they’ve been monitoring rising variants. So because the borders opened, the assorted Omicron sublineages have dominated, and extra just lately there’s been the emergence of a number of recombinant sublineages, and these are lineages arising from the change of chunks of genetic materials between strains, and these recombinant lineages at the moment are dominating.

So which sublineages are significantly an issue proper now, and the place do they stand in comparison with the sublineages that we had been earlier than?

There are a number of of those designated by the Pango designation, which is a nomenclature system for SARS-CoV-2 lineages and sublineages. And those which might be circulating now start with the letters XBB, after which varied numbers relying on the sublineage. So there are a number of so-called variants of curiosity as assigned by the WHO, corresponding to XBB.1.5, XBB.1.16, and EG.5, which is an XBB descendant, which might be circulating.

So the sublineages, why does that matter to us?

Genomic surveillance is essential as a result of we have to control which lineages are circulating, in order that if there is a sudden rise in a selected emergent pressure, or a rise in severity is famous, that we all know what is going on on and we all know early.

It is usually stated, if we do not look then we can’t know.

That is precisely proper.

Let’s speak about issues at a affected person stage first, after which we’ll get onto the genomics. Fast antigen checks. They’ve grow to be the mainstay of our method to COVID testing. Inform me slightly bit about them. Ought to we nonetheless be counting on them? How efficient are they with the present sublineages?

Fast antigen checks had been a extremely essential instrument, significantly across the time the borders opened when case numbers had been very excessive and laboratory PCR testing capability, or nucleic acid amplification testing capability, was saturated. And so these offered a method by which individuals in the neighborhood may take a look at themselves and have a end result inside 15 to half-hour and be capable to enact an applicable remedy or public well being response to having been recognized. So significantly at the moment, they had been very important.

They do have some limitations. The sensitivity of those speedy antigen checks is decrease than for nucleic acid amplification checks or PCR checks. Sufferers with very early an infection could also be destructive and will require repeat testing in 24 to 48 hours, or a nucleic acid amplification take a look at as a extra delicate take a look at to substantiate the end result. Today with decrease case numbers, there may be laboratory capability for PCR or nucleic acid amplification testing, and being a extra delicate take a look at than RAT, the place it is possible, that is a greater take a look at to do.

So perhaps you possibly can inform us slightly bit about why speedy antigen checks have inferior sensitivity to PCR testing. Does that must do with the best way that we acquire the checks, or is it actually one thing a bit extra technical than that?

It is to do with the character of the assays themselves. So a nucleic acid amplification take a look at, in a basic sense, these are very delicate assays. They detect the genetic materials, so both the RNA or DNA, in a medical specimen, and so they’re capable of detect very small quantities of the fabric. What they do is, following DNA or RNA extraction, there is a collection of thermal cycles which lead to amplification after which detection of the assay goal. Whereas a speedy antigen take a look at, that is detecting an antigen part of the virus itself via a lateral movement immunoassay, and so it is detected visually. And there isn’t any amplification of fabric as a part of that step, and so it is a much less delicate method, however nonetheless has cheap sensitivity. To be eligible for registration on the TGA, the final I regarded, the minimal sensitivity in comparison with a nucleic acid amplification take a look at required for registration was at the very least 80%. So not too dangerous, however they may miss some instances.

I am glad that we have better accessibility to PCR testing now. And what you have stated actually makes plenty of sense by way of attempting to know cycle thresholds and different issues that we have began to grow to be acquainted with as we have had higher entry to PCR testing.

Yeah, that is true. So I discussed the character of PCR checks is thru various thermal cycles that lead to amplification of the gene goal. The cycle threshold is the primary a type of cycles at which the PCR product is first detected. So the upper the quantity of pathogen genetic materials within the specimen, the decrease the cycle threshold shall be. So it is inversely associated to the viral load, basically.

These cycle thresholds fluctuate between PCR assays. There’s an enormous variety of PCR assays on the market, every with completely different gene targets, and the cycle thresholds aren’t comparable between assays. And that is why we do not report these in our pathology experiences for PCR checks. Nevertheless, they will present some useful data typically. A really excessive cycle threshold, for instance, 35 cycles or larger, that might both point out very early an infection, or it may point out persistent low-level shedding of non-viable viral fragments following an an infection. And that may happen for various weeks following acute an infection.

So when you have a PCR end result that is optimistic with a really excessive cycle threshold, the advice can be to repeat that take a look at within the following 24 to 48 hours. If there is a drop in cycle threshold, that will be in keeping with acute an infection. Nevertheless, if it is persistently very excessive, then that might point out probably previous an infection. Nevertheless, these outcomes must be interpreted within the medical and epidemiologic context, by way of the affected person’s signs, their comorbidities, and so forth. So there’s probably not a tough and quick rule for decoding these, and so they’re not routinely reported.

So total, this lab-based nucleic acid amplification testing, PCR testing, when ought to we be utilizing this clinically? What function does it play in our medical armamentaria?

PCR testing or nucleic acid amplification testing is probably the most delicate technique to diagnose COVID-19, and can be the beneficial take a look at for sufferers in hospital for high-risk contacts or healthcare employees, the place there are critical penalties in case you miss a prognosis so, for instance, the place there could be a false-negative RAT.

Typically it will get prompt that sufferers who’ve destructive speedy antigen checks ought to have a PCR completed if they have actually apparent signs, if they have clinically evident an infection. What do you consider that technique, and do you assume that is one thing that we would be carrying with us as we go ahead?

If a affected person is suspected to have COVID-19 and so they have a destructive RAT, then ideally you must do a PCR take a look at or a nucleic acid amplification take a look at to substantiate that end result. Another technique, if a nucleic acid amplification take a look at is not out there, can be to repeat the RAT in 24 to 48 hours.

One of many different benefits of a PCR take a look at is that we will get genomic knowledge, which we clearly cannot get from speedy antigen testing. How widespread is genomic testing in on a regular basis PCR testing, and the way a lot ought to we be doing?

That’s one consideration. Within the first two years of the pandemic, a really giant proportion of COVID-19 instances had a specimen despatched for genomic sequencing, and that is as a result of at the moment we had been monitoring and tracing each case, whereas as soon as the borders opened, there wasn’t the capability to sequence all instances. And so a genomic sequencing technique was developed by the Communicable Ailments Genomics Community, prioritising instances with extreme illness, instances with reinfection or recurrent an infection or persistent an infection, returned travellers, and likewise outbreak investigations. These are the precedence specimens, and there is ongoing genomic surveillance as we mentioned earlier, monitoring the variants and so forth.

That brings me on to this dialogue about different winter viruses as properly. We’re more and more in a world the place a affected person would possibly current with signs that might simply be not simply COVID however influenza or different winter viruses. Looks like we’re testing which may more and more seize all of these in a single swab.

Yeah, that is proper. So for the primary couple of years of the pandemic, different viruses, significantly influenza A and influenza B, disappeared basically altogether. Nevertheless, as soon as the borders reopened, as you’ll anticipate, these viruses re-emerged, and have been circulating during the last 2 winters. Most laboratories supply multiplex nucleic acid amplification testing, that are assays capable of detect various viral pathogens, and a few additionally embrace bacterial pathogens as properly. And this enables syndromic prognosis and identification of the commonest viral pathogens with only one take a look at. So these have been beneficial the final couple of winters. Extra just lately, there have been some speedy antigen checks for influenza A and B accepted by the TGA. Just like the take a look at for SARS-CoV-2, there are some minimal efficiency necessities, such that they must have minimal sensitivity and specificity. Nevertheless, as for SARS-CoV-2, they’re much less correct than the nucleic acid amplification checks.

We have had influenza for a very long time, however we’ve not had speedy antigen checks for influenza till now. Is that this one thing that we have realized from our COVID expertise? I’m positive there are a variety of issues that we have realized from our COVID expertise that could be relevant to different winter viruses.

The COVID-19 pandemic actually was an distinctive scenario, and there have been various classes realized round implementation of diagnostic testing and scaling of diagnostic testing for respiratory viruses. I believe one of many keys to profitable administration of the pandemic was the early availability of the total genome sequence of SARS-CoV-2, which enabled the design of nucleic acid amplification checks. And so we had delicate and particular checks out there from very early on. Australia’s fortunate that we’ve a extremely sturdy regulatory system for pathology testing. Nevertheless, there have been applicable provisions made for emergency growth and rollout of checks, and the existence of the Public Well being Laboratory Community and Communicable Ailments Genomics Community enabled sharing of experience, sharing of management materials for take a look at validation and growth, growth of a top quality assurance program for comparability of laboratory efficiency. And this actually was key to us having the ability to diagnose and hint these early instances and management the pandemic.

From a genomics perspective, the infrastructure for genomic sequencing had been in growth on the varied public well being laboratories. The AusTrakka platform, which is used for genomic sequence sharing, was in growth, and the pandemic accelerated that, and it was rolled out from very early on, enabling inter-jurisdictional knowledge sharing. So all of this was very important for our take a look at, hint, and isolate method to public well being administration.

Nevertheless, on the time that the borders opened in late 2021 and with that Omicron wave, that is when the speedy antigen testing actually grew to become essential, and the power for sufferers to check themselves, and having the regulatory framework that enabled TGA registration of these checks, rolling these out meant that we had been capable of proceed diagnosing instances even when the laboratory and nucleic acid amplification testing capability had been reached. Since that point, as case numbers have dropped, I believe the speedy antigen checks are probably slightly bit much less essential, however they nonetheless have a task.

The place antigen testing for different viruses suits within the scheme of issues, I believe it’s nonetheless not 100% clear, as a result of on the finish of the day, the nucleic acid amplification checks are extra delicate and a greater take a look at actually for diagnosing these viruses, if it is out there.

Let me take slightly pivot there and ask you about one thing which is faster than a traditional lab-based PCR, however is clearly extra delicate than a speedy antigen take a look at, and that is point-of-care nucleic acid amplification testing. Have we realized slightly bit about how we would use that form of expertise higher? Has that expertise superior through the COVID pandemic? And do you assume that matches into our total long-term technique?

That is a extremely essential level. Actually point-of-care checks for SARS-CoV-2 had been essential in some settings, significantly emergency departments and distant clinics, for instance. In order that assisted with an infection management choices in emergency departments, the place there have been restricted single rooms or destructive stress rooms, for instance, and likewise for distant clinics the place there is a delay in testing related to specimen transport. Having delicate and particular nucleic acid amplification checks that had been simple to make use of, however importantly operated underneath the NPAAC [National Pathology Accreditation Advisory Council] governance necessities for point-of-care checks, so nonetheless with essential high quality measures in place, having these point-of-care checks out there was actually useful and I believe did forestall transmission in some situations.

It feels like we have realized quite a bit about testing for viral respiratory infections all through the COVID expertise thus far. Do you assume that this actually informs a method that we take care of the following viral respiratory an infection epidemic or pandemic?

I believe undoubtedly. What we have realized is the significance of speedy growth and rollout of high-quality diagnostic checks, however with applicable high quality administration of that testing in place is absolutely essential for having the ability to diagnose instances, after which subsequently enact the suitable public well being response.

I am very glad that you just and your colleagues are doing the good work that you’re. So thanks a lot, and thanks for becoming a member of us on the podcast as we speak.

Thanks a lot.

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The views of the company and the hosts on this podcast are their very own and will not characterize Australian Prescriber or Therapeutic Pointers. I am David Liew, and as soon as once more, thanks for becoming a member of us on the Australian Prescriber Podcast. [This interview was conducted on 28 August 2023.]