How might the B.1.1.529 variant (Omicron) affect the Isle of Man?

It’s been nine months since I’ve blogged so today you’re getting my lunchtime musings on the new variant B.1.1.529 Omicron and some actions we could be doing on the Island to ensure we’re prepared for it.

Yesterday (25th November 2021) the South African government were open and transparent with the world and let us all know they had detected a new variant with a significantly large number of new mutations circulating in several areas of South Africa.

  • Why is the scientific community taking so much notice of this new variant compared to the many others which are still occurring throughout the world?
  • How could that affect the Isle of Man over the next few months?
  • What is the current status of our defences against vaccine-escaping variants on the Island, given the current strategy is entirely vaccine based?

It’s not so much that the new variant carries so many new mutations that makes us scientists sit up and listen. It’s the data that is showing that it is more transmissible than Delta, the current variant dominating UK infections, and the data which suggests it may reduce response to COVID19 treatments. The data also shows it may be capable of immune escape i.e. it can get past the vaccinations or significantly reduce the effectiveness of the vaccinations.

The data from SA also suggests that B.1.1.529 Omicron may be rapidly outcompeting Delta to become the dominant variant there. When COVID has radically changed like this in the past – for example when Alpha first emerged in Kent – the first theory is one of emergence from an immunocompromised patient with a chronic infection which gave the virus an opportunity to mutate further. In this scenario the patient goes on to infect people with their new variant. The second theory is one where testing and genomic surveillance is low and, as such, transmission without testing and surveillance naturally leads to a “blind spot” which when genomic surveillance is finally carried out shines a light on previously untracked infections.

Having looked at many ssRNA viral genome assemblies and phylogenies in my career I’m inclined to think that B.1.1.529 Omicron may have originated with the first theory given the branch lengths on the tree. As with anything in science, if I see more data then my opinion might change.

While this variant has emerged from an area where there is low vaccination coverage it’s not yet known how it will fare in a country with high vaccination coverage. Given the large number of mutations across the B.1.1.529 Omicron genome there is a strong suspicion that it will cause infection in vaccinated people. Time will tell but it’s better to be safe rather than sorry and this is why countries are reacting by closing their borders to travellers from affected countries.

What’s the current status on the Isle of Man?

There are a number of changes which have been made over the last six months under the political “living with COVID” banner which mean that we are dangerously susceptible to the effects of a new variant like B.1.1.529 Omicron.

The “living with COVID” rhetoric has led to virtually no mitigations being in place other than vaccination. The strategy should always have been “vaccination plus masks” but the messaging of the vaccination campaign has led to our population discarding masks as a mitigation method. This is one of the primary reasons for our current case rate.

Adding to the lack of mitigations is a level of complacency in testing methods and strategies which leaves us wide open to the risks posed by new variants like B.1.1.529 Omicron.

  • Gold standard PCR testing has been restricted in favour of less sensitive LFDs and subsequently PCR has been wound down to negligible levels.
  • The hospital is now using LFDs for admissions instead of PCR, opening up the possibility of COVID transmission within the hospital given the big difference in false negative rate between the two types of test.
  • The second PCR test that the path lab are using to determine variant (instead of genomic sequencing) is substandard and not fit for purpose.
  • The detection PCR tests in use by the path lab do not detect one of the proxies that can be used to identify positive samples from lineages such as B.1.1.529.

What does this mean in lay terms? We’re not detecting the cases we do have, we’re not testing enough with decent methods, we can’t detect new variants, we specifically can’t detect B.1.1.529 Omicron on-Island with the PCR tests in use, and the hospital is at risk of an outbreak on the wards.

If B.1.1.529 Omicron were to be introduced then it could rapidly replace Delta as the primary variant on the Island and if the immune escape data turns out to be proven then it would affect the effectiveness of the current vaccinations. This would lead to sicker people, more deaths and more risk of overwhelmed health services. If this were to occur it would require significant mitigations be put in place until one of the vaccines – likely one of the mRNA ones – could be amended to cover this variant and be distributed throughout the population as a booster. This is why the UK government immediately put SA on the red list, which is not without it’s ethical considerations, as the openness and transparency shown by SA was rewarded with border closures from the rest of the world (but that’s another post for another time).

What can the Isle of Man do to prepare for the arrival of B.1.1.529 Omicron or other new variants?

There are a number of issues that need to be urgently addressed if we are to be prepared for new variants of concern such as B.1.1.529 Omicron hitting our shores.

Number 1: The low uptake of booster vaccinations needs to be addressed immediately

I’m not sure how eight months ago we were perfectly able to know who needed vaccinating and coordinate appropriate appointments but now we are not able to coordinate booster vaccinations in the same way. Remember, we spent almost half a million pounds on vaccination hubs, yet our booster take-up is very poor. Recent research is showing that the booster at six months is key to protecting ourselves from serious illness with Delta. That suggests it will be just as important for new variants. If we can’t roll out boosters rapidly and successfully how will we cope with an B.1.1.529 Omicron specific booster if needed quickly? We can’t lock down unvaccinated/unboosted people until the DHSC gets around to vaccinating the population against a new variant. Nor should we accept any deaths while the good ship DHSC takes a leisurely slow turn.

RECOMMENDATION 1: We should not be complacent in the face of B.1.1.529 Omicron. There needs to be responsibility and accountability within the DHSC for increasing our booster levels up from 37% to >80% of the population as fast as possible.

Number 2: If the DHSC won’t fund PCR testing properly then we need to be using LFD tests which are sensitive enough to detect infection in infected people

I am hearing an increasing number of reports of symptomatic people testing negative with the government-issued lateral flow tests who are testing positive with other brands of lateral flow test a few minutes later. The same patients are also subsequently testing positive with PCR.

LFDs are only useful if they work and are as specific and sensitive as they need to be for the application they’re being used for. Assuming that all brands of LFD are the same is a fallacy (as is thinking all PCR tests are the same).

RECOMMENDATION 2: Immediate review into the on-Island laboratory testing carried out to determine the best LFD to roll out for public use. Did our own testing show that the selected LFD is sensitive enough to detect an acceptable number of positive cases to use it as a PCR replacement? If not, why not?

Number 3: Re-introduction of PCR as the COVID screening test for hospital admissions

This one is about as obvious as it gets. We do not want Nobles hospital to be another Abbotswood. If LFDs are testing negative in positive patients in the community then it is only a matter of time before it happens on the wards and isn’t caught for a few days. “Nosocomial infection of COVID” (i.e. the patient got infected in hospital) isn’t a phrase anyone should be hearing on the Island. PCR is used for detection of other pathogens in hospitals so why are we OK with NOT using it for the one pathogen which is currently of interest? Money shouldn’t be making these decisions but if that’s the way it has to be then think of it this way: PCR is cheap but extended hospitalisation from a nosocomial COVID infection is expensive. Just like that age-old 2020 phrase “testing is cheaper than a lockdown”.

RECOMMENDATION 3: Reintroduction of PCR testing for hospital admissions.

I have already recommended, through the EAG, that the variant-detecting PCR in use at the path lab should be stopped (chocolate teapot came to mind) and I could write an actual book on why genomic sequencing is going to be key with the variant detection and why masks are the most effective mitigation for reducing spread and thus case numbers.

However, I can see the brick wall and I’d like my forehead to still be intact going forward.

In conclusion, the Isle of Man needs to start preparing for B.1.1.529 Omicron coming to our shores, sooner rather than later. We can’t keep relying on the UK to do the work for us. We shouldn’t be work-shy in doing our own Island-specific contingency planning for things needed in the face of a vaccine evading variant like ramping up PCR testing to thousands per day, assessing testing methods to make sure they work for the application we want to use them for, and vaccinating as much as possible.

Unfortunately if the world does the right thing with B.1.1.529 Omicron and controls its spread then the vocal minority of naysayers will say that scientists were “scaremongering”. I’d rather we were accused of that, having done the right thing and have it work, than being responsible for not doing anything and watching the case rate and death rate increase.

One thing to be sure of with this virus (and variant) is that it’s better to be safe than sorry.

The 30 minute calculation David Ashford says is a “waste of resource” to calculate

During my morning coffee and news catch-up routine I came across this article from Manx Radio, published yesterday:

My first thought was, “hang on, didn’t the Treasury calculate this only weeks ago to figure out the cost of the testing for returning travellers, to explain why they pay for their own testing?”. Hmm.

So I have two questions:

  1. How did the Government calculate that covering traveller’s COVID tests would have costed £420,000 per month if the Government had paid for it?
  2. How much does a COVID test provided by the IoM Government actually cost?

I’m just about to start my morning coffee break. So for a bit of nerdy fun let’s see how long the “waste of resource” calculation takes me.

Question 1: How did the Government come up with the £420,000 per month figure?

This one is easy. The article from 20th January 2021 says that in “November and December the average number of people moving through the Island’s ports was around 700 a week“.

We’re calculating for a month (4 weeks), so 700 x 4 = 2,800 people.

When we divide £420,000 by 2,800 people we get £150, which is the cost of three COVID tests (day 1, 7, 13). This puts the cost of a test at £50, exactly what is charged to those people who are paying for the tests. NB, the day 1, 7, 13 testing regime didn’t start until 23rd December. The borders are now back to level 5 so very few people are now travelling via this route. The same testing strategy is not being used for residents who ring 111 and report being symptomatic, key workers on special testing pathways, or people being tested prior to a surgical procedure.

So to come up with this figure the Government just extrapolated from what they currently charge people for a test by the average travellers per week in Nov/Dec.

But this figure could change dramatically if the cost per test changes. This leads us onto the next question.

Question 2: How much does a COVID test actually cost the Isle of Man Government?

As I run a commercial molecular diagnostics company (i.e. we design, develop and deploy tests professionally) this is a standard calculation and one we carry out routinely. If we didn’t carry out these exact calculations for our suite of 183 PCR tests on a regular basis we wouldn’t still be in business. I would have expected the NHS to also know how much every test in a pathology lab costs and how many they carry out, if only to be able to budget accurately for the following financial year.

In the case of Isle of Man COVID testing, there is the cost of the PCR test itself, any equipment purchased, the staffing costs of providing the service and the cost of consumable items like swabs, pipette tips, tubes and other plasticware.

So let’s itemise all these things and calculate a figure.

I’m making a number of assumptions but always calculating the most expensive option for all assumptions made so the real cost per test to the NHS will be cheaper than any figure I end up estimating.

  • Assumption 1: 60 people per day being swabbed at the Grandstand. This number could be higher or lower but based on the current daily testing figures seems appropriate. Obviously, the more people who are swabbed the lower the cost of the swabbing facility is per test. These 60 people are returning travellers, people who ring 111 with symptoms, and those due to have a surgical procedure or other pre-booked hospital admission.
  • Assumption 2: 20 patients per day being admitted to hospital, or being prepared for transfer to a UK hospital are being tested with the 1 hour “rapid tests”. These tests are excluded from this calculation as the DHSC know how much each of these tests cost – approximately £100-120 per test – and how many they are using per day as they’re a limited resource.
  • Assumption 3: Commercial list prices for everything. However, the NHS can purchase much more cheaply than this through NHS supply chain.
(Assumptions and working out is listed below each item)
Price per test
Being swabbed at the Grandstand.
* 2 Healthcare assistants and two registered nurses running the drive-thru. Top end of band 3 (HCA) salary is £27k gross, Top end of band 5 (RN) salary is £37k gross. This equates to approximate gross cost per hour of £14.50 per hour (HCA) and £20 per hour (RN) based on a 37.5 hour week.
* Gross salary costs per hour for the team = £69/hour
* Assumes the DHSC are not paying rent on the grandstand, given the nature of the testing.
* £69 x 3 hours = £207. £207 / 60 patients swabbed = £3.45 per patient swabbed.
The swab used to swab the patient.
* Based on this price list (which will always be more expensive than the NHS can buy for) and rounded up by at least £1. The swab being used for COVID testing is product MW951S.
Isolating the viral RNA from the swab
* The only cost to the Isle of Man NHS here is the plasticware (pipette tubes, sample trays) as the pipetting robot was bought with Charity funds and the magnetic bead extraction kits are provided for free though NHS supply chain.
* Plasticware for 60 samples assumed to be 2 x Fisherbrand 1ml deepwell plates (£3.78), 1 x 200ul PCR plate (£4.46), 5 racks/refills of pipette tips (£18). Total for the RNA extraction run = £26.24
* £26.24 / 60 samples = £0.45. Let’s round that up to a pound to be on the safe side.
The COVID19 PCR test
* When Taxa Genomics was providing reagents the cost was £7.15 per test (which was three PCR tests in the same tube). I have it on extremely good authority that the current PCR in use at Nobles is a little cheaper than this (because it doesn’t test for the presence of human RNA to check the swabbing and reduce the false negative rate) so we can safely assume £6 per test or less.
* The PCR test will also require 1 x 200ul PCR plate (£4.46)
* £6 per test + (£4.46 / 60) = £6.10. Let’s round that up to £6.50 to be on the safe side.
* The real-time PCR machine was found in the Government Analyst’s lab and so was FOC. A larger machine with 4x capacity was purchased by a Charity in Aug/Sep ’20 but is not in use (i.e. all PCR equipment costs aren’t factored as they were free to the DHSC)
Pathology laboratory staffing
* Assuming a band 6 Biomedical Scientist (BMS) and a Band 3 Medical Laboratory Assistant (MLA) per day, exclusively working on COVID PCR testing. Top end of Band 6 BMS salary is £44k gross, top end of Band 3 MLA salary is £27k gross. This equates to approximate gross cost per hour of £24 per hour (BMS) and £14.50 per hour (MLA) based on a 37.5 hour week.
* Gross salaries for a day of testing with one PCR run = £288.
* Gross salaries per sample (assuming 60 samples per day) = £288 / 60 = £4.80.
* The cost per sample decreases the more samples that are processed

A few months ago I estimated (on the fly, on Twitter) that the cost per test was about £25, because that’s a comparable figure to our in-house testing here at Taxa. I would still say that now that I’ve spent 30 minutes doing the calculations, despite it coming out at £7 cheaper on calculating the list prices.

So at £25 per test I’m massively over-estimating the cost per test here. **It has been suggested on Twitter that I double the staffing costs (even though they’re based on maximum of salary band) to account for other costs. Fair enough, that takes the total test cost to £27 per test, which is a massive overestimation, on top of a costing that was wildly overestimated to start with.**

So why does David Ashford keep asserting that the cost per test is £100 and where is the other £75 per test being spent?

I’m genuinely intrigued!

p.s. this took me half an hour, including searching the job centre website for salary bands, suppliers for list prices and writing the blog post…

COVID genomics on the Isle of Man: the history

Copyright Rachel Glover. If you want to use sections of this text ask first.

Get yourself a cup of tea, this is a long post and could take a few minutes to read. It’s been rather a nice exercise in pulling together lots of historical information, emails, papers and powerpoint presentations to aid my memory of what was a rather hectic time! It came about because earlier this evening I was asked on twitter about what I thought about IoMGov sending samples to Liverpool for genome sequencing. The reply was going to be far too long for a series of tweets, so here it is.

Needless to say I’m not going to sling any mud in this post, so if you’re thinking that you’ll get all the gory details of how badly I was treated by the DHSC for volunteering my expertise you won’t find them here. Saying that, when the Isle of Man Government inevitably pats themselves on the back for such an amazing genomics achievement at some point in the future, spare a fraction of a second for my blood, sweat and tears that brought them to the point where they even knew such techniques existed.

If you want a quick potted overview of what a genome is and how we can use them then download this presentation. I gave the keynote at this year’s UCM Festival of Research on 17th September and the download is a pdf of my slides. There might be a recording somewhere on the UCM website (I think).

Basically, genome sequencing is the only way to tell the difference between all the different lineages of COVID, including the “new” UK variant. The PCR test used to detect the virus in infected people can only say “detected/not detected”. Genome sequencing is super-high resolution testing that can, effectively, tell who gave it to who.

There’s a tiny bit of very basic science at the end of this post showing a small part of the IoM genomic analysis I did (and can get away with putting here) to make reading to the end worth your while 🙂

For many years I sequenced and analysed viral genomes for the UK Government (in addition to designing tests for them). I was at the cutting edge of viral genomics at the time (with 454 for those of you who know what that is) but if you want to take a look at small section of the work I did, take a look at my publication record. Our team was carrying out applied sequencing of ssRNA viruses routinely from 2009 before the clinical crowd looked at its real-world application in about 2013-14 during the Ebola outbreak in West Africa. So viral genome sequencing is my rather specialised bread and butter.

Back in February this year I did a Manx Radio interview on Women in Science day (I’m a LoveTech mentor) and at one point managed to get into conversation that COVID19 viral genomes were being sequenced worldwide to track the spread of the disease. Skip to 3 minutes on this link to hear me talk about how genomic epidemiology can be used for COVID, amongst other things.

A few weeks later I sent the now-infamous email that would change the course of my 2020 completely. It was an email to Steve Doyle (the head of the path lab at Nobles Hospital) offering to set up on-Island testing for them so that samples didn’t need to be sent to Public Health England in Manchester any more. I could write a book about how I went about doing that, but I digress. During that first week in the path lab, while Steve was still figuring out the best way to pay me for my time and expertise, I was making noises about sequencing the virus from whomever was unlucky enough to become the first positive patient identified on the Island.

On 22nd March I sent out the email below with this rather informative document (worth a download and was the first of many in those couple of weeks during setting up the lab) to Steve Doyle, Rizwan Khan and Rebbeca Shields at the DHSC. I was pretty sure we would get a positive patient in the next 3-5 days. The first positive case on the Island was identified two days later when the result came back from PHE from the swab taken from a patient on the 17th March.

As you can see, I was rather keen to get sequencing viral genomes as soon as I had on-Island testing up and running. Genome sequencing was always present on the agenda of those update documents.

At this point, not only was I carrying around two genome sequencers in my rucksack every day, awaiting the opportunity to use them, but I had also transferred a batch of viral genome sequencing reagents to the hospital lab “for emergencies”. I had been in touch with some old colleagues from the UK (notably Nick Loman (@pathogenomenick) and David Studholme (@davidjstudholme)) as I knew they were heavily involved in the newly formed COVID-19 Genomics UK Consortium (aka COG-UK). The Isle of Man doesn’t get included in these projects due to our non-UK, non-EU academic funding status but I wanted the IoM to be part of it and wanted to find out how we could get involved.

On 31st March 2020 the first patient samples were tested on-Island but the launch of total on-Island testing didn’t happen until three weeks later on the 20th April (lots of reasons, mostly government procurement related that I might talk about in future). During this time I had to assess the current skill sets of the biomedical scientists (which varied), identify the immediate training needs, and move and set-up robotic equipment belonging to Taxa Genomics in the hospital lab to automate the process as far as possible so that the biomedical scientists didn’t have to try to learn advanced molecular techniques within days that could go wrong without automation. I was also fielding hundreds of emails from various IoM Government, DHSC, Department of Enterprise and Nobles hospital staff asking for advice on various COVID19 tests, should they buy this-one-or-that-one, what is this new technology etc. Often these emails came to me second or third hand, with my answer being repackaged as an answer from whomever asked me for my input. It annoyed me that I wasn’t being asked directly but in hindsight, I know now that there are plenty of ego’s in the DHSC who wanted to pass my knowledge and expertise off as their own. It’s also worth remembering that during this whole period I was also running Taxa Genomics at a point where our DNA testing sales tripled during lockdown (!). Sleep was elusive, never mind viral genomics.

In the middle of May I saw that another scientific acquaintance had published a rather awesome paper using COVID19 viral genomic epidemiology to track transmissions in Australia. The next time I saw Steve I showed him the paper and told him we should be doing this on the Isle of Man. I assumed he would bring it up with Rizwan and Henrietta (Director of Public Health) at their (unofficial) testing strategy meeting on the 25th. When I heard nothing back I tried another tack and emailed Henrietta directly, copying in Rizwan and Steve.

This email was received positively and with some excitement by Henrietta and the team at IoM Public Health as the genomic analysis of the first outbreak could inform any changes in policy needed for any future outbreak. It could also be used in “real-time” to inform decisions on the ground during any future outbreak. However, it went down like a lead balloon within the path lab. I was given what could only be described as an email bollocking for ignoring a “chain of command” that I didn’t know existed. Henrietta invited me along to a section of their testing strategy group on the 16th June to discuss further. Rizwan was particularly annoyed about me going straight to Henrietta so I offered him final authorship on any papers I wrote about COVID19 genomics as a sweetener.

On 19th June myself and Rizwan had a meeting with Al Darby and Kathryn Jackson from the genomics facility at Liverpool uni, who were carrying out the COVID19 sequencing for the COG-UK project on samples from PHE Manchester. I was pretty sure a bunch of the Isle of Man samples tested at PHE Manchester would have already been sequenced, and it turned out I was right. But this opened an ENORMOUS can of worms.

You see, the COG-UK project only had ethical approval to test and analyse samples from patients in the UK. They hadn’t realised that there could be samples already sequenced by them and in the public domain that were from other jurisidictions not covered by their ethical approval. Which meant that before we could access the publicly available (anonymised) COVID19 genomes from the Isle of Man patients we would need our own ethical approval from the IoM Cabinet Office / Public Health. Only then would I be able to start matching the genomes up to patients, their contact tracing data and subsequent antibody status (my master plan for the first genomic epidemiology paper to ever be produced by the Isle of Man).

That in itself seemed like a simple, if drawn out, process. Write the ethical R&D application where I promise to make sure that patient data is fully anonymised, stored securely and that no-one would be able to be identified from any published analysis etc. Get approval, start doing some science. Simple, right?

Not simple. The can of worms was opened further. No-one had ever considered the legality of samples being sent to UK reference laboratories before, even though the hospital had been doing it for decades. Apparently all Isle of Man samples sent to reference labs in the UK had been sent illegally (in theory) because the legislation did not exist to cover these scenarios. Then there was the matter of consent. Had patients consented to the virus sample they gave being tested further? At first it looked as though we would have to retroactively consent all ~300 patients to ask if it was OK for us to test the samples further. That would have been complicated given a number had sadly passed away from their infection. Thankfully saner heads prevailed and the expected push back from the Attorney General’s office was countered with prior examples. Isle of Man samples containing Salmonella spp. and Mycobacterium spp. had been whole genome sequenced for typing at reference laboratories in the UK on many previous occassions and it was argued that COVID19 was no different. Dr. Rebecca Rowley in IoM Public Health was an absolute star throughout this whole period (it took weeks) and arranged for the Caldicott Guardian to sign off the legal side of things so that I could finally submit the ethical approval application for consideration. Phew!

Cue a long wait while the ethics application was written, submitted, assessed, amended and finally approved in September 2020. In the mean time the microbiology lab chucked out a bunch of those precious positive samples that needed to be sequenced on-Island. I still don’t the how’s or why’s considering they had been fastidiously saving positive samples at my request for genomics since March. I’ll probably never know.

Once the approval was through I was able to get my teeth into some of the data available on the public databases. I had spent time with Madeleine Sayle in IoM public health making sure that they retained the contact tracing data and working out the data management strategies for tying everything up computationally to aid my analysis. There were a few frantic emails in September making sure the contact tracing data from the original outbreak wasn’t deleted by the Information Commissioner! The small amount of genomics work that I did before I resigned was presented “hot off the press” to MHKs and MLCs at Tynwald on the 27th October, having literally analysed it the day before. I didn’t know when I presented it that I would resign in utter frustration later that evening, but I’m glad it was seen by a few people before I left! When I recorded the public version of that talk and uploaded it to YouTube I omitted the slide with the preliminary genomic results just in case there were any confidentiality issues I hadn’t considered. Ultimately, though, the data was open access and on a public database in the form I present it below.

There were 34 COVID19 genomes available from patients on the Isle of Man at first, representing all positive samples from the 17th March 2020 to 26th March 2020. If you remember, the border was closed on the 27th March so this was a great little starter dataset. I can’t present much of my analysis here as I can’t identify any patients, nor show any of the information I know about the clusters now that I’m no longer working for the DHSC. But the part that I can show gives a rather nice little diagram we call a phylogenetic tree.

Each genome is identified with it’s anonymous identifier, then the lineage assigned, followed by the date the sample was taken.

I’m assuming 99% of you reading this aren’t scientists and so I should explain the image above. It’s basically a clustering of the virus genomes based on how similar they are genetically. Samples that cluster together are highly likely to represent transmission chains between contacts, families, households or social gatherings. I know what a few of those are but can’t divulge. What it does show is that there appear to have been potentially 16 introductions of the virus to the Island in the 10 days before the border was shut. Many of these introductions will have gone on to transmit further in the community. There may also have been introductions of the virus from people who were never tested. There’s so much more to this and the initial analysis I did but I can’t put it online!

I would have loved to link to the open data with some amazing visualisations (like these here) but in recent weeks the Isle of Man data has mysteriously disappeared from the public databases. I’ll let you draw your own conclusion on that one – let the conspiracies start!

It’s a sad situation where I wasn’t able to achieve one of the main things that would have made the Isle of Man look scientifically advanced especially given that my company has all the equipment, reagents and expertise to carry out on-Island COVID19 genome sequencing in real-time. But it is what it is.

COVID testing explainer 2: What is a false negative?


I’ve seen a lot of comments on various Isle of Man facebook groups over the last few weeks where people are claiming their negative SARS-CoV-2 test result must be a “false negative”. So let’s delve into the testing and what “false negative” really means.

The first thing to know is that a SARS-CoV-2 PCR test result is reported as either:


As you can see the lab doesn’t use the words “positive” or “negative”. When a PCR test is carried out, it either detects the virus or it doesn’t and that’s how the results are reported to your doctor.

This paper shows that infectiousness starts around 2.5 days before COVID-19 symptoms start and the peak viral load (the amount of virus) occurs about half a day before symptoms start. By the time you start to show symptoms (and therefore become eligible for a test through the IoM 111 line) there should be an awful lot of virus present at the back of your nose and throat for detection. Detectable (but possibly non-infectious) viral RNA also hangs around in there for at least two weeks and even up to a month. PCR testing helps to differentiate people with COVID-19 from people with colds and flu so that they can be contact traced and the spread of SARS-CoV-2 contained.

All PCR tests have something called a limit of detection which is the lowest number of copies of the virus that the test can detect. The test we use on the Isle of Man has a limit of detection of 10 copies of the virus, which is very sensitive.


A possible weak point in SARS-CoV-2 testing is the swabbing. The nasopharyngeal swab that needs to be taken to collect the virus has to go really far back into the nose. It’s not very pleasant (but thankfully only takes a few seconds) and there’s the potential for a false negative result if the swab doesn’t collect enough cells. However, the testing we do on the Isle of Man actually takes this into consideration and tests the amount of human RNA present on the swab as well as the SARS-CoV-2 RNA. If the level of human RNA is below the threshold we established during our validation testing the result is reported as INSUFFICIENT SAMPLE and the patient is asked to have a new swab taken.

If we didn’t do the human RNA test then a small proportion of the low quality samples could be from patients with COVID-19 but could be reported as negative because the lack of material in the swab reduced the amount of virus below the limit of detection of the test. These would be false negatives and given the potential for a false negative person to spread the disease thinking they’ve had a negative test, we introduced the human RNA check on the Isle of Man to minimise the risk of false negatives as much as we possibly can.

So what does “false negative” really mean?

Well, there’s bit more to it than just that term and what most people assume it is. There are really four different terms to understand: true positive, true negative, false positive and false negative. 


Let’s look at hypothetical Bob who was thought up by me and doesn’t exist in real life.

Bob has had a cough for a few months, sees the symptoms of COVID-19 on the news and decides to ring 111 for a test. He says the cough is new. The test result is “SARS-CoV-2 NOT DETECTED”. A few days later he gets infected with SARS-CoV-2 after a sneaky visit to his friend’s house during lockdown (bad Bob). At day 5 he becomes infectious and at day 7 he starts to show symptoms of COVID-19. He calls 111 for a second test and his result this time is “SARS-CoV-2 DETECTED”.

Bob assumes that his first test is a false negative and tells his mates on facebook that the test is rubbish.

But bad-boy Bob is wrong. His first test was a true negative and his second test was a true positive.

So no false negative for Bob.

As you can see, a real false negative is a patient who has COVID-19 disease but where the PCR test does not detect any SARS-CoV-2 virus (usually due to insufficient swabbing) rather than a true negative followed by a true positive. Despite the facebook rumours, real false negatives are actually pretty rare because of the human RNA test we carry out, the limit of detection and the known sensitivity of the test in patients with COVID-19 disease (99.4%).

So in conclusion, the likelihood is that if your test came back negative you had something else like a cold or the flu, not COVID-19.

COVID19 testing explainer 1: What is a virus?


This post is intended as an explainer for the general public

To understand how the testing works we first need to understand what a virus is and how each species of virus differs.

Viruses can infect all types of life, not just humans. There are viruses that infect animals, plants, and even ones that infect bacteria. Viruses infect life forms, but they’re not considered to be either alive or dead themselves. They’re really quite clever little hijackers. They gain entry to a host cell and then use the cell’s own molecular machinery to make more copies of the virus using a genetic blueprint of instructions contained inside the virus. The cell then becomes a microscopic virus factory which ultimately bursts and releases all the new viruses it just made. The new viruses then go on to infect other cells as the infection progresses. The ultimate aim of a virus is to make as many copies of themselves as possible, and often cause chaos along the way which we call disease.

We classify organisms by splitting them into groups – a taxonomy – based on their characteristics. The groups get split into smaller and more specific sub-groups until all the similar organisms are grouped together. Virus taxonomy splits viruses by how they look (morphology), how they copy themselves, what kind of genetic material they have, which organisms they infect and even the type of disease they cause.

The first big split in virus taxonomy is whether the virus genetic material is DNA or RNA. You’ve probably heard of DNA because it’s the same language our own genetics are written in. It’s made of four letters: A, C, T and G. RNA is a similar molecule but the T is replaced with a U. DNA and RNA can be both double stranded or single stranded.


SARS-CoV-2 (the proper name for the virus causing COVID-19 disease) is a single stranded RNA (ssRNA) virus. This type of virus tends to mutate quite quickly and rather than “strains” they tend to form something we call a quasispecies. The mutations accumulate over time as the virus infects more people and this means that we can track the infections using genomic epidemiology techniques by comparing the full genome sequence of the virus (the A, C, U and G letters) of all the different isolates. If you’d like to see more info on this have a look at the Next Strain website, it’s where the scientists are putting the genome data during the outbreak. I’ll put a post about genomic epidemiology on my to-do list.

The letters in the SARS-CoV-2 genome code for the instructions to make the proteins of the virus. This is comparable to having the blueprints to build a house. The virus hijacks the host cell and uses it’s molecular machinery to make more copies of itself. As an aside, this is why computer viruses got their name as they’re malicious code which likes to replicate itself. The RNA inside SARS-CoV-2 codes for a number of proteins which sit on the membrane of the virus as well as for enzymes which do the copying of the instructions themselves (the RNA-dependent RNA polymerase, or RdRp).


Once we know the sequence of letters in the viral genome we can start to design tests to detect it using those letters to our advantage.

It’s alive!

The Rachomics Blog has started!

I’ve been wanting to set up a blog for about, oh, 12 years or so. I was previously a scientist within the UK scientific civil service so blogs weren’t exactly something that were welcomed.

These days, I run a molecular diagnostics company (Taxa Genomics) and my collaborative work with the Isle of Man Department for Health and Social Care during #COVID19 has prompted me to look again at finding the time to do some science outreach. Plus, 93% of you said you’d read it. I’m going to hold you to that.

Let’s face it, I love science and think that everyone else should too, given how much it impacts our daily lives (even if we don’t realise it some times).

I promise I won’t swear (too much).