“Between the devil and the deep blue pool…”

Pooling of COVID-19/SARS-CoV-2 samples has been an important and integral part of the NZ laboratory response to COVID-19.

Two weeks ago, following the appearance of COVID-19 cases in the community following a 100 day hiatus, test volumes surged  nationally from 4000 samples to 27000 samples a day, literally overnight…

It goes without saying that without widespread pooling of samples, we would have had testing backlogs of several days if not weeks, completely devaluing the usefulness of the results in terms of contact tracing and significantly increasing the risk of exponential growth in the outbreak.

Microbiologists, by nature, are purists. They understandably want their laboratory to produce the “perfect” result. Accreditation agencies may have similar views, with a narrow focus on the quality of the results produced. That’s their job after all…

But the world, and in particular the COVID world that we now live in, is far from perfect, and we need to keep looking at the big picture.

Pooling of clinical samples for a PCR assay has a small effect on sensitivity. Because we measure virus counts on a logarithmic scale this effect is almost, but not quite negligible, if a small number of samples are pooled. We have the potential to miss “positive” samples with very low viral loads, likely coming from patients who are almost certainly non-infectious. In my anecdotal experience, most of the results produced at the limit of detection are in patients who are recovering from infection, in the recent or not so recent past. Our experience shows that the loss of sensitivity by pooling samples is probably less than using a throat swab instead of a nasopharyngeal swab.

The other potential drawback of pooling is that if you get a positive pool, you then need to test all the samples in the pool individually. If positivity rates are high then pooling becomes self-defeating, creating even more work! However positivity rates in NZ have up until now been very low, so this has not been an issue for us.

As far as I am aware, NZ diagnostic laboratories that have utilised pooling (most of them) have validated the methodology over different platforms to the best of their ability, within the considerable time and resource constraints they have had to work within. In addition they have implemented IT solutions to facilitate the pooling of samples from a pre-analytical point of view.

Registration and molecular staff all over the world have been under the pump recently due to COVID-19 testing. Long, long hours, validation of new assays and platforms, pressure to get results out quickly… It is tough and I am in utmost admiration of our molecular team. Pooling is one of several ways to reduce this pressure on staff and try and prevent burnout. COVID-19 and the associated high testing volumes are not going to go away. This was always going to be a marathon effort, not a sprint, so testing processes need to be sustainable in the long term.

COVID-19 is a new disease but pooling of laboratory samples is not. The thing that has become very clear with regards to this infection, is that effective control depends to a large degree on testing large numbers of people and getting the results out quickly so that appropriate isolation and contact tracing can be performed. We should be embracing policies that allow us to achieve this goal.

Up until now at my own lab, our largest volume molecular test was Neisseria gonorrhoeae/Chlamydia trachomatis PCR, approximately 60,000 tests per annum. SARS-CoV-2 test numbers are going to completely and utterly dwarf this!

We need to adapt, in a pragmatic and realistic fashion, to the situation that we are currently faced with.

Michael

There are plenty of examples of SARS-CoV-2 pooling studies out there. Here is one for starters!

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