“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!

“Influenza in NZ 2020: Gone AWOL…”

We are currently heading towards the end of July, which is well through the winter respiratory virus season in the Southern Hemisphere. And still we have not seen any Influenza (or RSV for that matter) circulating in New Zealand. At first I thought it was the lockdown through March and April which was blocking viral transmission through social distancing. However we are now a couple of months post-lockdown… Social distancing has essentially all but disappeared and still there is no Influenza and RSV in New Zealand. This must be now due to the fact we have a closed border and the fact that nobody can currently enter New Zealand without staying in a quarantine facility for 2 weeks on arrival. This seems to be blocking any potential influenza and RSV introductions into NZ*

The winter respiratory virus season still has a couple of months to run here, but things are looking very promising. An average influenza season in NZ causes an average of 400-500 fatalities. There is little doubt that RSV will also cause significant mortality in those with advanced respiratory disease and in the frail elderly. I would suspect that respiratory viruses as a group would count for well over 1000 fatalities per annum in NZ, not to mention several thousand hospital admissions. In contrast the 22 COVID-19 fatalities, although tragic, seems a meagre toll…

Clearly we (NZ) cannot keep our international borders closed indefinitely, because human nature will simply not allow it. We do however have to be very smart about re-opening our borders, using all the risk mitigation tools we can lay our hands on. We have a nation of 5 million COVID-19 virgins to look after, but that is another story.

When the borders do re-open can we still control the winter influenza season? We may not be as successful as we have been this year but I think 2020 has shown that control of seasonal influenza is entirely possible by trying to minimise “introductions” and their subsequent effects.¬† I would suggest the following measures:

  • Having a low threshold for testing, treating(oseltamivir) and isolating¬† travellers coming back into New Zealand who have respiratory symptoms
  • Influenza & RSV in returning travellers should be notifiable to Public Health so that the appropriate measures can be taken.
  • Influenza vaccination should be strongly encouraged for travellers coming into New Zealand, particularly those coming from the Northern Hemisphere
  • Routinely vaccinate all children to further reduce the chances of transmission, should any introductions occur

Put quite simply, we set the bar too low for seasonal influenza control in NZ. We regard the winter influenza season as an inevitability. We shouldn’t. We are a small island nation, and our COVID-19 response has shown that we can be united and disciplined when we want to be!

“We set the bar too low for seasonal influenza control in New Zealand”

Let’s make the NZ winter influenza season the exception as opposed to the rule…

Michael

Interestingly rhinoviruses, although much suppressed during the lockdown period, survived and are now flourishing, and possibly filling a niche created by the influenza and RSV vacuum. See this interesting blog post from Australia

 

“The Remote Microbiologist”

I have been doing some work from home during the New Zealand COVID-19 lockdown period.

With 6 children, 4 cats and a dog at home, this is not always easy! I barricade myself in one of the bedrooms (no office), put a sign on the door (see above), put on some headphones to dull the screams and yells outside, and get down to work…

Clinical microbiologists can do a good proportion of their work remotely. Any work that involves sitting in front of a computer or attending meetings can be done at home with the right equipment. I would say this comprises about 80% of my total workload.

The other 20%, such as reviewing culture plates and Gram stains, familiarisation with new testing platforms, performing AMS ward rounds, infection control ward reviews, and giving educational presentations require me to be either in the lab or hospital. With the digitalisation of culture images (Kiestra TLA) and Gram stains, this percentage may well decrease even further. We do have the Kiestra TLA in our lab, I just need to organise remote viewing…

I think the 80/20 breakdown of remote/in-house work is realistic.

We convince ourselves that we always need to be “present” in the workplace. But for clinical microbiologists this is just not the case. Of course it is nice to talk to and meet people face to face but it is not absolutely necessary to be physically in the lab every day. And I have lost count of how many times I have driven 1 or 2 hours just to meet with people who I could have spoken to via teleconference/videoconference.

Being an introvert, I must admit I am not a huge fan of teleconferences and videoconferences. I need those non-verbal signals that one can only pick up from being face to face. But I must say I have started to get used to them. When you are doing 2 or 3 Zoom (or similar) meetings a day, you have no choice in the matter really.

So I think when the lockdown in NZ finishes, the new “normal” will likely not be as before. I will have a lower threshold for working from home when I don’t absolutely need to be at the workplace (also saving precious time on the commute), I will think twice about driving long distances for meetings and I will try and continue to embrace videoconferencing technologies.

And all the children will be back at school so I will get some peace!

Michael

What do other clinical microbiologists think?