---
title: "Covid PCR"
description: "CBRNe World provides those tasked with defending against CBRN and IED threats with the essential practical, scientific and political information. Access the current and previous issues of the magazine by registering as a member."
url: "https://cbrneworld.com/news/subscribers/covid-pcr"
date: "2026-07-30T21:06:29+00:00"
language: "en-GB"
---

#  Covid PCR

 Written by Gwyn Winfield on 22 April 2020.

## **We’re in the middle of a (polymerase) chain reaction**

### Gwyn Winfield on what will happen to PCR post Covid-19

As distasteful as it is to state, Covid-19 will leave some people winners, and some people losers. The losers are pretty obvious, the families devastated by loss of loved ones, jobs and financial security, and the businesses wiped out, while the winners may take a while longer to ascertain. Clearly manufacturers of N95 masks will be short term winners, but looking further ahead another will be the capability to swift and efficient test and identify the pathogen on a mass scale. While we might yet see an effective antibody testing system become involved in worldwide [testing](https://www.wired.com/story/opinion-to-end-the-pandemic-give-universal-testing-the-green-light/), polymerase chain reaction (PCR) will be a certain winner. Now, I’ll assume you already know about PCR considering that it has been around for 30 + years… but if you don’t I’ll leave you in the capable hands of

[PCR Dance video](https://www.youtube.com/watch?v=67BVKjjE1fU)

Yet while PCR is leading the diagnostic fight against Covid-19, it has also suffered from a [series ](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136155/)[of ](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082661/)[problems](https://www.sciencedaily.com/releases/2020/04/200409144805.htm). For such a well understood technique why are we seeing such failures, what is happening between humans and PCR to cause false negatives? Like many elements of the fight against Covid-19, there is no clear answer, but a lot of ideas (check out [PCR Online](https://www.pcronline.com/Cases-resources-images/Zoom-on/Covid-19-19) for dedicated PCR/Covid-19 papers).

Firstly you have to realise that pressing the ‘run cycle’ button on the PCR is the final element in a chain of events. The first step is actually getting a sample from the individual. If you look at footage from South Korea or Germany you will see them using nasopharyngeal swabs, which are long swabs that go deep into the nose until the eyes water! It’s not the most pleasant of experiences but still does not offer 100% certainty of obtaining pathogen. Coronavirus sputum is another possibility, but since Covid-19 produces a dry cough this can be difficult to obtain. Some PCR companies have been looking at saliva, but this is heading into uncharted territory, and while it is a lot easier on the patient and sample taker, verification of the process will take a while. All this might not be uniform, however. Certain sampling methods may work better with different types of patient at difference stages of their illness, and these different samples will work better with certain PCR machines.

Having got the adequate sample onto the business end of swab it then needs to reach the lab. For that some kind of transport medium is required so the sample is kept alive until it is cycled and prepared for PCR. Not all viral transport media are the same, and with a shortage of correct transport media (and swabs for that matter) in the supply chain people are forced to [experiment](https://www.genomeweb.com/pcr/coronavirus-sample-collection-tool-shortages-will-be-short-lived-according-suppliers#.Xpmua25FxPY) with what they can get. The problem with experimenting with the ‘wrong’ types of swab or medium is one of [inhibition](https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2672.2012.05384.x). PCR is a great technology when you treat it right, but if you start breaking from procedure and use calcium alginate swabs or the wrong formulation of Copan's Universal Transport Medium , then you won’t find the droids you’re looking for. Co-infection can also be a problem for some PCR devices and result in competitive inhibition. If you have a variety of pathogens in a sample/patient, and have sensitivity issues with your PCR, then you might find that one pathogen outperforms the Covid-19 element, and you start to lose the signal.

Then there’s the assay, the ‘secret sauce’ of the PCR that is going to allow the potentially minute sample to be found among all the rubbish RNA/DNA that will be in the sample. In normal times the accuracy of the assay would be the making or breaking of a PCR company. Put out an assay with low accuracy and you can expect to be trolled by your peers for years. Now, with the suppliers of PCR machines, assays, transport media and swabs unable to meet demand, there’s of a ‘Wild West’ springing up. Individuals will sit at their computers and design a test, throw it against the databases, and that will be the limit of their inclusivity and exclusivity testing (remember that Covid-19 comes from a bigger family than SARS and MERS). They might get a little purified RNA from a bank of samples and then use that as their test for limits of detection. Previously if they submitted such results to the Food and Drug Administration (FDA) they would have had their wrists slapped, but due to the Centers for Disease Control and Prevention (CDC) bungling its own testing [regime](https://www.forbes.com/sites/rachelsandler/2020/03/02/how-the-cdc-botched-its-initial-coronavirus-response-with-faulty-tests/#277b13cb670e) the FDA has no real alternative to approving these things to try and meet the demand. Poor assays equals poor results.

If you are unsure about how much sample you have and the way the medium and swab react with the PCR, along with an ineffective assay, then it is no surprise that there have been reports of dissatisfaction with the technique. It is a global social experiment, with PCR at the heart of it, and in the interest of bringing this experiment to a swift conclusion people are following non-canonical paths.

This rather frantic period will, thanks to social distancing, come to an end sooner rather than later. Swabs and medium will eventually appear in satisfactory amounts for the devices. Maybe even more will be understood about the virus so that swabs can be taken from the right place at the right time, to ensure that there is sufficient pathogen for PCR to work efficiently. All this will allow the current generation of PCR to work properly… but what will the next generation of PCR look like? A lot of grant and venture capital money is sloshing around for improving these devices, so is there a chance we’ll see a revolutionary improvement in PCR?

I think that's unlikely for such a mature technology, but what we will see is an optimisation of PCR for this pandemic. Many of the PCR devices, like Biofire’s Film [Array](https://www.biofiredx.com/products/the-filmarray-panels/filmarrayrp/), are set up to test a range of agents from one individual, which is what we might consider normal diagnostics: someone’s turned up with a mystery ailment and the doctor needs to know what it is. Now, PCR needs to be set up to test for one pathogen, but from a range of individuals. The technology is the same, but the application is different. There will be a shift to high throughput platforms, like Bio [Rad](https://www.bio-rad.com/en-uk/category/real-time-pcr-detection-systems), dealing with volume processing. There is also some excitement about [Cepheid’s ](https://www.cepheid.com/coronavirus)new test which (like Biofire) offers the opportunity to bring cycle times down to under an hour, allowing swifter processing of individuals. Also market forces will bring some of the smaller, innovative companies into the orbits of the bigger ones. Thermo Fisher’s purchase of Qiagen has to be seen in the light of its [QIAstat-DX](https://corporate.qiagen.com/newsroom/press-releases/2020/20200226_coronavirus) test, as well as its other good work. This is likely to mean that whereas previously PCR companies could exist and proliferate selling one diagnostic device, now there will be fewer reputable suppliers selling a wider range of instruments.

That’s not to say that there won’t be a bloom of new PCR devices. Inevitably smart people in universities across the world will get funding to launch their own slight spins on PCR, though these are unlikely to see the light of day for dealing with the pandemic. PCR has been around long enough to be well understood so inevitably national champions will spring up in developing countries at a national price point and with a suitable delivery time. They might not work as well as Thermo Fisher and Roche devices, but they may work well enough to become regional champions and take root.

The financial wherewithal of the larger companies is also required to keep trialling and applying new things that we find out about the virus. Whereas the large companies are slow to adapt they understand how to navigate [510k](https://www.fda.gov/medical-devices/device-approvals-denials-and-clearances/510k-clearances) clearance and meet large customer requirements, and have baseline studies on their panels and devices to enable expert users to appreciate what they can do. They often have the advantage of faster access to the virus and research than the smaller outfit do, are at the front of the line for spares and reagents, and have their reputations at stake.There’s a lot to be said for small and nimble, but in this response the volumes and duration of the pandemic is likely to give the rosette to the bigger boys.

The most likely benefit from the money that is now available for improvements, and some estimate there is $2.5bn, will be in the PCR infrastructure. Parts of the supply chain will become ruggedised, freeze dried reagents for example, there’ll be a massive increase in PCR technicians, and the whole process, including the device itself, will become faster and more practised. The other major benefit is that - hopefully - there will be enough PCR devices floating around that they will start to migrate out of hospitals and into general practitioners’ offices, meaning that post Covid-19 diagnosis of mundane conditions will become faster.

This is perhaps the major technological concern out of what comes next. States that invest in high throughput single agent/Covid-19 devices might deal with this pandemic fantastically… but not so much with the return to normality. Inevitably the capability will be mothballed and put aside for the next pandemic, which could be in five or 50 years, by which time a great deal of that capability (without regular maintenance) will be degraded. The inclusion of Covid-19 into the broad respiratory panels, like Qiagen or Biofire, is what will aid the community in the long run.

Covid-19 might not see a revolution in the technology, it is too mature for that kind of shift. Neither is the market ready for a new, untested technology – there are too many variables in the population/pathogen, the threat is too high and time too short. Improvements can be made in how the technology is used, and excellent case studies for this will soon be coming from South Korea and Germany, and this will be best short term win rather than any technological improvement.

 [Detection](https://cbrneworld.com/component/tags/tag/detection)

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Now, I’ll assume you already know about PCR considering that it has been around for 30 + years… but if you don’t I’ll leave you in the capable hands of  PCR Dance video Yet while PCR is leading the diagnostic fight against Covid-19, it has also suffered from a series of problems. For such a well understood technique why are we seeing such failures, what is happening between humans and PCR to cause false negatives? Like many elements of the fight against Covid-19, there is no clear answer, but a lot of ideas (check out PCR Online for dedicated PCR/Covid-19 papers). Firstly you have to realise that pressing the ‘run cycle’ button on the PCR is the final element in a chain of events. The first step is actually getting a sample from the individual. If you look at footage from South Korea or Germany you will see them using nasopharyngeal swabs, which are long swabs that go deep into the nose until the eyes water! It’s not the most pleasant of experiences but still does not offer 100% certainty of obtaining pathogen. Coronavirus sputum is another possibility, but since Covid-19 produces a dry cough this can be difficult to obtain. Some PCR companies have been looking at saliva, but this is heading into uncharted territory, and while it is a lot easier on the patient and sample taker, verification of the process will take a while. All this might not be uniform, however. Certain sampling methods may work better with different types of patient at difference stages of their illness, and these different samples will work better with certain PCR machines. Having got the adequate sample onto the business end of swab it then needs to reach the lab. For that some kind of transport medium is required so the sample is kept alive until it is cycled and prepared for PCR. Not all viral transport media are the same, and with a shortage of correct transport media (and swabs for that matter) in the supply chain people are forced to experiment with what they can get. The problem with experimenting with the ‘wrong’ types of swab or medium is one of inhibition. PCR is a great technology when you treat it right, but if you start breaking from procedure and use calcium alginate swabs or the wrong formulation of Copan's Universal Transport Medium , then you won’t find the droids you’re looking for. Co-infection can also be a problem for some PCR devices and result in competitive inhibition. If you have a variety of pathogens in a sample/patient, and have sensitivity issues with your PCR, then you might find that one pathogen outperforms the Covid-19 element, and you start to lose the signal. Then there’s the assay, the ‘secret sauce’ of the PCR that is going to allow the potentially minute sample to be found among all the rubbish RNA/DNA that will be in the sample. In normal times the accuracy of the assay would be the making or breaking of a PCR company. Put out an assay with low accuracy and you can expect to be trolled by your peers for years. Now, with the suppliers of PCR machines, assays, transport media and swabs unable to meet demand, there’s of a ‘Wild West’ springing up. Individuals will sit at their computers and design a test, throw it against the databases, and that will be the limit of their inclusivity and exclusivity testing (remember that Covid-19 comes from a bigger family than SARS and MERS). They might get a little purified RNA from a bank of samples and then use that as their test for limits of detection. Previously if they submitted such results to the Food and Drug Administration (FDA) they would have had their wrists slapped, but due to the Centers for Disease Control and Prevention (CDC) bungling its own testing regime the FDA has no real alternative to approving these things to try and meet the demand. Poor assays equals poor results. If you are unsure about how much sample you have and the way the medium and swab react with the PCR, along with an ineffective assay, then it is no surprise that there have been reports of dissatisfaction with the technique. It is a global social experiment, with PCR at the heart of it, and in the interest of bringing this experiment to a swift conclusion people are following non-canonical paths. This rather frantic period will, thanks to social distancing, come to an end sooner rather than later. Swabs and medium will eventually appear in satisfactory amounts for the devices. Maybe even more will be understood about the virus so that swabs can be taken from the right place at the right time, to ensure that there is sufficient pathogen for PCR to work efficiently. All this will allow the current generation of PCR to work properly… but what will the next generation of PCR look like? A lot of grant and venture capital money is sloshing around for improving these devices, so is there a chance we’ll see a revolutionary improvement in PCR? I think that's unlikely for such a mature technology, but what we will see is an optimisation of PCR for this pandemic. Many of the PCR devices, like Biofire’s Film Array, are set up to test a range of agents from one individual, which is what we might consider normal diagnostics: someone’s turned up with a mystery ailment and the doctor needs to know what it is. Now, PCR needs to be set up to test for one pathogen, but from a range of individuals. The technology is the same, but the application is different. There will be a shift to high throughput platforms, like Bio Rad, dealing with volume processing. There is also some excitement about Cepheid’s new test which (like Biofire) offers the opportunity to bring cycle times down to under an hour, allowing swifter processing of individuals. Also market forces will bring some of the smaller, innovative companies into the orbits of the bigger ones. Thermo Fisher’s purchase of Qiagen has to be seen in the light of its QIAstat-DX test, as well as its other good work. This is likely to mean that whereas previously PCR companies could exist and proliferate selling one diagnostic device, now there will be fewer reputable suppliers selling a wider range of instruments. That’s not to say that there won’t be a bloom of new PCR devices. Inevitably smart people in universities across the world will get funding to launch their own slight spins on PCR, though these are unlikely to see the light of day for dealing with the pandemic. PCR has been around long enough to be well understood so inevitably national champions will spring up in developing countries at a national price point and with a suitable delivery time. They might not work as well as Thermo Fisher and Roche devices, but they may work well enough to become regional champions and take root. The financial wherewithal of the larger companies is also required to keep trialling and applying new things that we find out about the virus. Whereas the large companies are slow to adapt they understand how to navigate 510k clearance and meet large customer requirements, and have baseline studies on their panels and devices to enable expert users to appreciate what they can do. They often have the advantage of faster access to the virus and research than the smaller outfit do, are at the front of the line for spares and reagents, and have their reputations at stake.There’s a lot to be said for small and nimble, but in this response the volumes and duration of the pandemic is likely to give the rosette to the bigger boys. The most likely benefit from the money that is now available for improvements, and some estimate there is $2.5bn, will be in the PCR infrastructure. Parts of the supply chain will become ruggedised, freeze dried reagents for example, there’ll be a massive increase in PCR technicians, and the whole process, including the device itself, will become faster and more practised. The other major benefit is that - hopefully - there will be enough PCR devices floating around that they will start to migrate out of hospitals and into general practitioners’ offices, meaning that post Covid-19 diagnosis of mundane conditions will become faster. This is perhaps the major technological concern out of what comes next. States that invest in high throughput single agent/Covid-19 devices might deal with this pandemic fantastically… but not so much with the return to normality. Inevitably the capability will be mothballed and put aside for the next pandemic, which could be in five or 50 years, by which time a great deal of that capability (without regular maintenance) will be degraded. The inclusion of Covid-19 into the broad respiratory panels, like Qiagen or Biofire, is what will aid the community in the long run. Covid-19 might not see a revolution in the technology, it is too mature for that kind of shift. Neither is the market ready for a new, untested technology – there are too many variables in the population/pathogen, the threat is too high and time too short. 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