Emma Ross
Good afternoon and thank you for joining us for the last session for 2020 of the Living with COVID-19 webinar series, with Chatham House Distinguished Fellow and Academics Authority, David Heymann. Today we’re going to be talking about COVID-19 tests, what they can do for us, what they can’t, who should get one, when does it not make sense, how reliable the test results are, what kind of decisions should or should not be made on the back of test results, etc.?
With us today to discuss these issues are two leading lights in the COVID-19 diagnostic test space. Rosanna Peeling is Professor and Chair of Diagnostics Research and Director of the International Diagnostics Centre at the London School of Hygiene & Tropical Medicine. Sergio Carmona is Chief Access Officer at FIND, which is a global non-profit organisation that drives innovation in the development and delivery of diagnostics for major diseases affecting the world’s poorest populations. And FIND is very much involved in developing and delivering all these COVID tests and especially to developing countries. So, welcome to Rosanna and Sergio and thank you so much for joining us today.
Before we dive in, I’ll just remind everyone that the session is on the record and questions can be submitted using the ‘Q&A’ function on Zoom. Upvoted questions, as usual, are more likely to be selected, so if you have a question that’s similar to one already in the ‘Q&A’, please upvote it, ‘cause I’ll be looking at the upvoted questions first. David, I want to start with you today, this time. As we can all remember, there was a mad scramble at the beginning of the pandemic to get hold of tests. It was almost a supply chain wars. There are now hundreds of rapid diagnostic tests emerging. I guess my first question, David, would be with the advent of vaccines, do we really need so much testing anymore? I mean, do they have a major role at this point or for much longer in the pandemic? So, what do you see as their role at this stage in the pandemic?
Professor David Heymann CBE
Well, thanks, Emma, and thanks to Sergio and to Rosanna for having joined us today. Regarding diagnostic tests, there will also be a need for diagnostic tests. A vaccine is one tool in the war chest against this infection and there will be many, many more tools coming along, but diagnostics are at the base of that and as you’ll hear from both Rosanna and Sergio, there are various types of diagnostics. There are diagnostics which can identify the virus that’s present in people and that’s useful, for example, in diagnosing people who have signs and symptoms of COVID, to see whether or not they actually have the infection, and if so, then they’re isolated and managed in a health facility. At the same time, surveillance systems, which are there detecting respiratory infection, also have to be linked with diagnostic testing to see whether or not the virus is present and whether those people need to be isolated and managed. It’s also important for other new and – other new ways forward in the pandemic and I know that the airlines are working quite closely together to try to see what testing strategies might be useful to see if virus is present in passengers before they travel and when they arrive in the destination country and also maybe three or five – three to five days after they’ve gotten off the plane.
So, diagnostic tests for virus will continue to be very important, moving forward, as will tests for antibody, and as you know, antibody is the marker that tells you’ve been infected with the virus. It’s the antibodies that are developed to the virus. They’re important, because with that, you can tell where disease has occurred in the past, but it’s also important, because it may be that as we begin to vaccinate people, we’ll need to know after vaccination whether or not the vaccination has taken and, therefore, antibody will be an indication that the vaccine has taken. However, there’s one caveat with that. We don’t understand yet whether those antibodies are what’s protecting people against serious illness or against infection. But they will have a role to play, I’m sure, and I’m sure Sergio and Rosanna would agree with me, in the vaccination strategies that are being developed. And in addition, we don’t yet understand whether vaccines only prevent serious illness in people who are vaccinated, or whether they actually prevent infection. And so, virus detection tests will be important, moving forward, in making sure we understand how vaccines work the best, as well.
So, the answer to your question, longwinded as it was, was yes, diagnostics will play an ever-increasing role in the fight against COVID-19.
Emma Ross
And I guess that’s tied up with the whole idea of vaccination proof certificates that especially if it doesn’t prevent you from becoming infected, but it may prevent you from becoming ill, if you get vaccinated, there will be a need for a test you may be infected after vaccination. So, do you see it, kind of, coming together, the two coming together, or – ‘cause a lot of people think, well, if you’ve just got proof you’ve been vaccinated, then you don’t need to test. But that would…
Professor David Heymann CBE
Yeah, sure.
Emma Ross
…only be if the vaccination prevents infection, is that right?
Professor David Heymann CBE
There’s lots to learn, yeah. What we would – what the perfect vaccine is, is one that prevents infection and prevents carriage of the virus in the nasal passages. And if you have a vaccine like that and it’s long-lasting, then a vaccination certificate might be useful at some point. But right now, we don’t understand enough to say whether or not vaccine certificates are useful, but I know that the airlines are also considering this in their work together to try to make travel even safer than it is today.
Emma Ross
Okay, thank you for that introduction. So, I think we can all accept that we still need tests and very much. So, Sergio, welcome. Can I turn to you now to walk us through where we are with diagnostic tests, in terms of what choices do we have today? I mean, how many are there to choose from, what types of tests are available, and which should be used when, the pros and cons, and what do they tell us and what do they not tell us? And have you got…
Dr Sergio Carmona
Yeah.
Emma Ross
…any notes of caution as to how they should be used?
Dr Sergio Carmona
Great, so, there are a lot of questions there and to elaborate from where David started, and the two big categories, tests that tell you, you had the infection, those that are based on antibodies, and tests that tell you, you currently have the virus. And it may be in that group there are two types, one that looks at the genetic material of the SARS-CoV-2 virus that causes COVID and the one that tells you, you have a protein or a structural element of the virus, right? So, there’s a genetic material one and one that detects a protein of the virus. Both of these tests can be deployed in various settings. Some require very sophisticated instruments that allow for that genetic material to be amplified, so-called PCR or nucleic acid amplification types of tools. And then, there’s the others that pick up the protein and those are the new ones that everyone’s talking about, these point of care test that are easier to use, that can give you a result in 15 minutes and do not require instruments, as such.
The PCR is very accurate, but the time for a result to become available is still challenging in many settings. So, here’s the benefit, between highly accurate, very specific tests, but takes you many days to get a result, versus a test that may be slightly less sensitive, if you want, but can provide a result immediately. And maybe going to David’s points earlier, that I would approach the – your question in two ways: do we want to use the test to treat a patient that comes with symptoms and manage it, confirm and see what the outcomes and risks are? Versus, as you pointed out, this testing that happens with people that may be asymptomatic or symptomatic in settings outside of their traditional health services? So, they have a role to play in many of these.
Now, how many are there? Well, this year, we’ve seen an amazing pipeline that has developed and in – by manufacturers and biotech companies. So, initially, there were just a handful, now we have over 100 or more of these tests and we, at FIND, have evaluated several of these, too. Depending on the regions you are, the FDA Emergency Use Authorization has a list, WHO as a list called Emergency Use Listing, and currently, there are at least two or three listed there that can be safely used and many others are in the pipeline being assessed for both accuracy, ease of use, etc.
But a point that I want to really stren – really hone in, is the value of rapid tests, in terms of the time of a result, right? So, you can then isolate an individual that could potentially infect others in 15 to 30 minutes and that has a major implication, at public health level, for containing this pandemic.
Emma Ross
Oh, okay, thank you, Sergio. I just wondered, are they all equally good? You said hundreds, and I’m wondering how does – especially when it’s – when people are buying the tests themselves, I mean, are they all equally good? Is there some standard agency that gives, like, a seal of approval that, you know, this one…
Dr Sergio Carmona
Sure.
Emma Ross
…is good and works well…
Dr Sergio Carmona
Yeah.
Emma Ross
…or do we not know?
Dr Sergio Carmona
So, WHO has issued, already, what they’ve called their “Target Product Profile”, with thresholds of what is the minimum acceptable as to – and versus a desirable threshold, right? So, we use that bar, if you want, both for sensitivity and specificity. And these are – it’s difficult, maybe, terms to use, but how good are they in detecting someone that is truly positive, versus someone it – that it isn’t and how, down in little particles, can they get to? And those thresholds have already been established by WHO and there are other organisations, like the FDA, that also have them. And we use that…
Emma Ross
But, like…
Dr Sergio Carmona
…to make…
Emma Ross
…is it marked on a test? I mean, can anybody – recipes, you know, that were uploaded on the WHO website of protocols for how to make a test, can anybody decide to make a test and sell it? Is anybody policing the quality of these tests, or is it buyer beware, from these hundreds of tests…
Dr Sergio Carmona
So, it…
Emma Ross
…we’ve all got to choose from?
Dr Sergio Carmona
So, Rosanna has got many years of experience in…
Emma Ross
Oh, okay.
Dr Sergio Carmona
…whatever…
Emma Ross
I’ll ask her about that.
Dr Sergio Carmona
…regulatory authorities.
Emma Ross
Okay.
Dr Sergio Carmona
I’m not – Rosanna, you know very well that field of the regulatory affairs, in many regions. Do you want to take that?
Emma Ross
Oh, unmute yourself.
Professor Rosanna Peeling
Okay, thank you. Thank you, Sergio, and we’ve never had this situation where we are faced with having over 800 some tests being commercialised. And so, every government is facing the difficulty of trying to sort out which are the good tests, and which are the bad tests. I think the leading authorities for that are – is the USFDA and WHO. But even then, you know, for the vials that are submitted to them for approval, it’s only for emergency use, only, which means that they’re – they don’t go through the kind of scrutiny that normally a test would go through in getting regulatory approval. And so, it’s really paper review on the what’s reported to these authorities about the sample size, about what the score standard is used, for comparison of the new tests against a standard.
We don’t have an international standard as yet for these tests, so it’s really a little bit difficult right now for a lot of countries, but if you go to the FIND website, you will see – you could filter out the tests that have been approved by various governments and the, normally, the stringent authorities are thought to be – the regulatory authorities are thought to be the FDA, and the Australian TGA, the Health Canada, Japan and the EU, and so, those are places where you could see which tests have been approved.
Emma Ross
Okay, so, is it really a buyer beware situation where there can be unapproved tests for sale? Are these 800-odd commercialised, are they all approved tests that have been commercialised, or that you’re just tracking – you’re aware of 800 tests out there that may or may not be approved by somebody? Or are they not allowed – is nobody allowed to sell an unapproved test?
Professor Rosanna Peeling
Well, in many countries where the regulatory authorities are not very stringent, then a lot of tests are being sold and used, without any evidence that they work and so, at least we know that the ones that are – have been submitted, the companies that have submitted their test to FIND, there’s a level of scrutiny, right, Sergio? They have to have at least a CE mark, so that we know that they comply with the international standard organisation Code of Conduct for manufacturing quality. But quite often, companies would submit vials on their accuracy, based on, you know, this – whatever panel they – of evaluation panel they could get their whole – get their hands on. And in this pandemic, you know, trying to figure out what are the specimens that could be used, it’s subject to a lot of variation. And so, for example, if I want to make sure my antigen tests looked good, I would use lots of samples with very high viral load and so, then, the tests looked like, you know, it’s 100% sensitive. But in fact, you know, in a normal population, you need to know, you know, how – you know, what is the limit of detection, right?
Emma Ross
So, yeah, that accuracy, actually, was going to be my next question to you, Rosanna and, you know, what I was hoping you could come in on is how much confidence can we have in any of these test results, especially if we get a negative result? I’m thinking about, you know, of course, some governments will provide tests, or offer tests, but some people may want to get tested off their own volition, but how sure can we be, how reliable are they, and what determines how reliable any result would be?
Professor Rosanna Peeling
Yeah, so, I think in general, for any tests, we talk about the sensitivity and the specificity of the test and the sensitivity is really some – both these values are actually inherent characteristics of the test. They don’t change at all, that is a property of the test, right? But when you apply that test to a population, then, you know, depending on the prevalence of disease in the population, then its predicted value changes, based on the relationship between the sensitivity and specificity and the prevalence of infection. So, for example, if you use a test for – a molecular test to try to confirm a COVID case in a patient presenting to hospital or presenting to a testing centre, with symptoms consistent of COVID in this pandemic, then the likelihood of that patient testing positive is anywhere from 30 to, you know, 50%/60%. And so, then the test has very, very high predicted values for telling you that it’s a true positive. But if you then use the same test in a population, in the general population and try to look for positives, then you may get, actually, more false positives than real positives. So, you know, the prevalence of infection in the population really has a lot to do with how the true – you know, how accurate your test results may be at the end.
So, what we’re saying is that, you know, if you are using a test, beware how you use a test in the context of your testing strategy, which population are you testing, what’s the likelihood this population would become positive? So, let’s take, you know, the – so, first, we have the symptomatic patients who are highly likely to become positive, therefore, you know, these tests – and WHO has set a minimum performance threshold for the antigen, the rapid antigen tests, as having a sensitivity of 80% and a specificity of 97%.
Emma Ross
Sorry, what’s that, that it picks up 8…
Professor Rosanna Peeling
Yes.
Emma Ross
…7% of cases?
Professor Rosanna Peeling
Yes, and will miss about 20% of them. And the specificity is would – it would assure you that when you have a negative test, it’s only missing 3% of those tests and so, I – you know, so, I think that it’s…
Emma Ross
Does that mean that the tests are out there comply with that, or not necessarily? That’s the standard…
Professor Rosanna Peeling
Necessarily.
Emma Ross
Is that the reality when you’re buying a test…
Professor Rosanna Peeling
No, no.
Emma Ross
…the chances of getting…
Professor Rosanna Peeling
Not necessarily.
Emma Ross
…a perfect result?
Professor Rosanna Peeling
Yeah, so, quite often, I mean, it’s – I shouldn’t say this as general statement, that what’s on the product insert as to the sensitivity and specificity may not be, you know, very accurate, depending on whether the company knows how to do these clinical evaluations. I’ve had, in the past, when I was at WHO, a company come to me with a rapid syphilis test, and said, “Our test is 100% sensitive and 100% specific.” And so, I said, “Great, that’s the test we need to screen pregnant women.” And I said, “How many patients did you have in your study?” And he was very – you know, he said, “Oh, you know, 100.” And I said, “How many are syphilis-positive?” And he said, “Three.” So, that’s – you know, to get three out of three positive, that’s not telling us a lot, because we are not very confident that, you know, it would have a, you know, I would say…
Emma Ross
Okay, so, this all goes to, and maybe I’ll go to David on this, of the public use of tests. Because, you know, with the arrival of these rapid tests and being able to buy them, we’d expect that a lot of people would be using them and determining their behaviour, their risk behaviour, based on the results they’re going to get from these tests. So, do you think that say you buy a test and it says you’re negative, coming up to the holidays now, it’s festive season and we want to mix the generations, but we want to protect our loved ones, if I get a – buy one of these tests and it says I’m negative, can I just relax and think okay, I’m not infected, I’m not a risk to my grandparents, I can kiss, hug them, everything will be fine? Is that what these tests – is that how we should be using them and is it safe to conduct ourselves that way and bring these tests into our lives in that way? You’re on mute, David.
Professor David Heymann CBE
Yeah, Emma, it’s all about personal risk assessment, and personal risk includes many different factors in addition to testing. So, if you’ve been at a Christmas party four days before you plan to go visit your grandparents, no matter what your test says, you should not go, because you might’ve become infected at that party and you could then infect your grandparents or your parents. It’s all a matter of where you’ve been that’s really the most important. So, if you’ve been staying at home for two weeks and you haven’t been exposed to any parties or any gatherings of people and you want to do a test to make sure that you’re not infected, then maybe you’d want that just for your self-assurance. But a test alone is no guarantee of being free of infection, because you could…
Emma Ross
But if you’re sat at home?
Professor David Heymann CBE
…be testing yourself, Emma, at the time before your test becomes positive, even. You know, it takes a while for tests to become positive.
Emma Ross
Meaning you can…
Professor David Heymann CBE
So, all of the…
Emma Ross
Test shows negative, but you are infected, does it mean…
Professor David Heymann CBE
That’s right.
Emma Ross
…it’s missed an infection, or does it mean that your infection hasn’t progressed enough? You know, to me, that’s a failure in the test, it’s got a false negative, or is it not that simple?
Professor David Heymann CBE
It’s not a failure in the test, it’s a fact that people don’t develop a high enough level of the virus to be detected by this test by the time they’ve been tested. So, if you were exposed two days ago and had an antigen test, a rapid test, today, the likelihood is that it would not be positive, even if you’re infected.
Emma Ross
Okay, so, does that mean you should test yourself again, or not bother?
Professor David Heymann CBE
Yes, that’s one solution is to test yourself again. But the most important is to take all the factors about yourself together as you do the risk analysis, not just to test. A test is for certain purposes, but it’s also dangerous to rely only on a test.
Emma Ross
But if you’re going to isolate for two weeks and you’re not going to see anyone, you never even need a test, do you, ‘cause you wouldn’t have been exposed?
Professor David Heymann CBE
Well, if you’re going to isolate and you want to get out of isolation sooner, you might try to think when your contact was and then, based on seven days after that, you might want to test yourself again. And if you’re negative, then you might want to argue that you could get out of self-isolation.
Emma Ross
Okay, so, I don’t know, fair enough, David, I don’t know which one of you can answer this question, but this is something, say you test positive for PCR, that means you’ve got the virus in you, does it mean you’re infectious, that you can give it to somebody else? Could you have the virus, but be past the point where you could spread it, or, you know, what do we make of this and what is a PCR actually telling you?
Dr Sergio Carmona
Okay, so that’s become very, very interesting question and we’ve known this also from other viruses, but now the evidence is coming along quite well, that a PCR-positive test it’s like a sliding scale, right? It’s how positive are you? I don’t want to get into too much of the technicalities, but PCR is so sensitive, it’s able to pick up such low levels of the virus. I don’t want to call it viral dust, but there cannot – but it depends entirely where you are in the curve, how to interpret that result and many settings interpret it differently. Some are quite categorical, in respect of how strong that PCR signal or night testing, or whatever it is, it will be called positive, right? And the difference here between an antigen RDT and PCR and that relationship between transmission is something that has now – and there are a couple of new meta-analyses or systematic reviews that are starting to show that not all PCR results, the very, very sensitive result, that it picks up very little of the virus, it’s unlikely to transmit to others.
But there’s also, as David points out, there’s also a viral cycle. We, in medicine, we never used to treat a pathology report, or results, right? We treat the patient or the individual, right? And you would need to know what’s the history of exposure, when did the symptoms develop, to interpret that result? So, we know that between day zero of the symptoms’ onset, to three to five, that’s when you’re most likely to be shedding a lot of virus and your PCR will be definitely positive, and so will be your antigen RDT or this rapid test. But later, that curve then starts flattening and maybe ten or 14 days after symptoms onset, your PCR may still be positive, but your antigen RDT may not. And that’s when you start distinguishing another result is wrong, it’s just that one is picking up leftovers of the genetic material of the virus and the other one is picking, probably more likely, viral particles that could transmit to others. So, it’s a time issue as well and maybe, and we’ll see how this looks, that the antigen RDT will correlate more likely with that contagious, or ability of the virus to infect others.
Emma Ross
So, it sounds really complicated, actually, and I’m thinking about how we might use test results, kind of, strategically. And, Rosanna, I want to come on to strategic use of tests, since that’s the real theme of what we’re discussing today. But I’m thinking how governments, or businesses, or whoever is judging, might use a PCR-positive test in order to exclude someone and – or even to politicise it, like, you know, so much in this pandemic has been politicised and infection status you can imagine could become one of those types of issues that if it takes such skill and professional expertise to be able to interpret and piece that together, it’s not just yes/no on a test result, do you see any danger in the way this is going forward and how this might be used or misused? Or do you think, as a group, because we’ve got the vaccine, that’s going to become a non-issue and we don’t have to worry about that? Is there a danger here in the way tests are being used?
Professor Rosanna Peeling
Yes, and just as Sergio has said, you know, different tests can tell us different things, but ultimately, we have to interpret a diagnostic test in the context of the patient, of the history, whether they have symptoms or not, what’s the expos – and what were exposure events that they’ve been exposed to recently, etc.? And so, I think there’s really a danger if we don’t have more science literacy amongst our policymakers and public health experts and they, together, need to agree on how to use these tests, so that the results are interpreted the right way. And if Politicians and public health experts, as we have seen in some countries, don’t agree and don’t use science as a basis for going forward, then the public is even more confused about it. And when the Politicians and the public health experts don’t agree, then the public has very little confidence in what the – you know, any restrictions, isolation or any, sort of, lockdown measures that countries decided to use. And then, we don’t have compliance with those and so, the epidemic would rage on in that case, regardless of how you test, how many people you test. And I, you know, personally, a lot of people have found this – have asked me, “How do you interpret my results?” And really, I have to ask a whole lot of questions before I could say, you know, yes or no.
I think, with regard to shedding, as Sergio says, the data is now coming forward. There’s been some small studies looking at using culture to see how long the virus becomes – it stays infectious and according to these small culture – studies on culture from people with viruses is that they usually are not shedding infectious virus after day eight from the onset of symptoms. But that’s only a general average. I think it varies a lot with people, with what viral load they have, etc., and so, it – there’s no simple answer, unfortunately.
Emma Ross
Well, we – God forbid. Okay, David, I wanted to ask you – so, actually, you could all speak to this, but I wanted to ask David first on this. Mass testing, so, several countries – and with the arrival of these rapid diagnostic tests that Sergio had alluded to or – and Rosanna, that they’re less accurate, I’d like to find out how much less accurate, how dodgy are they, in terms of accuracy? But what do you think is the wisd – is there a wisdom to pursuing mass testing? Is it a good idea and will it totally transform our lives and how we get through the rest of this pandemic, once we have mass distribution of these tests? Is it safe to use mass testing with these rapid tests to return to normal life, David?
Professor David Heymann CBE
Well, Emma, I think it depends on what the goal of that testing really is. Every testing strategy has to have a goal and it’s never been clear to me what a testing strategy is, if you want to test your entire population. What do you do with the people who are positive? Do you force them to isolate? Do you ask them to isolate? Do you exclude them from society? It just needs to be thought through very clearly before you start testing. Early in the pandemic, countries were saying, “Oh, we’ve done a million tests today, we’re very – in very good shape.” Well, that means nothing, really, to me, or to an Epidemiologist. What it means is, I did a million tests because I wanted to see how many people in that million people, in that million population were infected, so that I could do something with them. So that I could isolate them, so that I could provide them guidance.
So, I think it comes back to why are you testing, which is important. If you’re testing an entire population, in order that you can identify those who are infected and remove them from circulation, that would be something, which would have to be studied by an ethical group before it’s done and by a whole series of other people involved in daily life, in the medical care of people, in health facility accommodation, a whole series of things, in order to determine whether or not that is a useful strategy. But that’s my view and I know Sergio and Rosanna will have other views, so, I would go to maybe Rosanna next to ask her what her view is.
Emma Ross
Yeah, and Rosanna, can you talk a little bit about strategic use of testing and what that means and what the concept is, and are countries, are they being strategic about it, or is it chaos, what’s going on?
Professor Rosanna Peeling
I think we – I don’t think any country has come up with a very clear mass testing strategy yet. As David says, there are many questions as to what type of mass testing do you do. Do you do antibody testing to find out what the true extent of the pandemic has been, or do you do virus testing or antigen testing to know how much viral load is still in the community, right, and what’s a force of transmission? And so, depending on these purposes, you need to think about, also, what tests to use, how to deploy them, what are the logistics of getting supplies to everywhere around the country? And that’s not a small thing, and logistic…
Emma Ross
Yeah, and these…
Professor Rosanna Peeling
…and…
Emma Ross
Correct.
Professor Rosanna Peeling
…you know, you have to do them in a limited time span otherwise it’s no good, right? And you need to do it as a snapshot and if you can’t do it in a very short time span, you elongate it to months and months, then the picture evolves so quickly, then you’re not getting a snapshot. And then, you know, there’s the cost, right? We’re trying to open up the economy, so that people can get their jobs back and get their lives back. Is that a good use of money to do the testing, or should you spend them on vaccines, should you spend them on compensating people who are unable to make the ends meet, etc.? So, there are so many questions about what a reasonable testing strategy should be [notification sound]. Oh, sorry.
Dr Sergio Carmona
And I don’t know, is that your alarm?
Professor Rosanna Peeling
Yes, but…
Emma Ross
Yeah, I don’t know who’s alarm. But Sergio, I’m going to…
Dr Sergio Carmona
You need to wake up.
Emma Ross
…move onto audience questions in a minute, but Sergio, if you want to come in on anything urgent on that? But other than that, if you think enough’s been said, I wanted to just squeeze in there the whole issue of quality control and the prospect of fake tests. Are – is there a concern with that, is it going on? Thinking back to the consumer, of how does a consumer make sense of all the 800, or whatever, these tests, and do we know it’s a real test and, you know, and if we’re doing it ourselves, is that okay? What are your thoughts on that? And then I’ll go onto…
Dr Sergio Carmona
Okay, so…
Emma Ross
…audience questions.
Dr Sergio Carmona
To open question. So, maybe we should qualify that the – what we’re talking about. So, this mass testing that is happening in the UK and also, in many other colleges, for example, in the US, those tend to be of two types: those PCR or genetic tests, and those are generally operated by pretty well-trained sophisticated professionals. So, the error likelihood there of getting the sample incorrect or getting a – you know, it’s a much more controlled environment. What I remember seeing a little bit about the UK is there’s two things: one, the self-collection, right? That you cannot get a brush, put it on your nose and send it in the post, or someone picks it up for you, versus it’s a professional collecting the specimen and sample and then doing a PCR. There’s a lot of variability in there that it’s not intricately a fault of the test that you may or not be using, right? And then, now, we know that the FDA has already approved one self-testing, which does the full end-to-end, right? You self-collect and you self-run it and you – a bit like a pregnancy test. And with that, obviously, if you don’t pick – if you don’t collect the specimen correctly, you – even a well-performing test, that is FDA – has all the bells and whistles from quality assurance point of view, can still fail, right? So, there’s – we need to distinguish those errors that come from badly used rapid test, versus those that are – it’s still within the professional – in the hands of professionals, but it could still give you errors.
In terms of fake and poor quality, this is what we used to call post-market surveillance. I think maybe WHO has a different name. Both for medicines and diagnostics, there are systems, and maybe more robust in some countries than others. Like constantly check fake tablets, fake diagnostics. I must say, with COVID, there’s been such a surge and such a massive effort in getting these tools out there, that I think the amount of post-market surveillance that needs to take place probably could be strengthened. We saw the bad press at the beginning of the pandemic on countries buying millions of antibody tests and then having to retract them. I think many countries have learnt from that and, hopefully, good measures are being put in place to address that.
How can the consumer protect themselves? I think through their own health regulatory authorities and see what’s available.
Emma Ross
Okay, thank you. I’m going to – I want to move onto audience questions now. The most upvoted question is from Louise Hart and she’s asking, “Currently, the rapid diagnostic tests are nowhere near as reliable as PCR swab tests. Do you anticipate the rapid tests improving in reliability in the same way that PCR tests have done in the past eight months?” And I – could, I guess, Rosanna or Sergio, kind of – we still haven’t got to the bottom of these rapid diagnostic tests, how inaccurate are they? I mean, are they missing one third, you know, of – are they giving a lot of false reassurance that you’re clean when you’re not, and what is the accuracy? And then, if you could please tack that on to answering Louise’s question. Who’s best placed to take that?
Professor Rosanna Peeling
Sergio, you want to try, or…?
Dr Sergio Carmona
Okay, let me give it a shot. I’m getting some tipping questions here.
Professor Rosanna Peeling
And then I can get involved.
Emma Ross
Well, can you start…?
Professor Rosanna Peeling
I could – well…
Emma Ross
Oh, can we ask for accuracy, so that we can see the difference between a PCR, the certainty and the result, versus these others? And I know with 800, or whatever, there’s a lot of variation, but vaguely, type of test and…
Dr Sergio Carmona
Yeah, so maybe I’ll keep it simple, right? So, as Rosanna put it, there’s 80% sensitivity and then 97. I’m trying to give you those numbers. So, that means out of 100 people, right? Maybe we’ll miss 20%. But that improves a lot when you’re just using the tests with those individuals that come, will tell you, “I developed symptoms yesterday. I’m not feeling well. I’ve got this sore throat, the fever, the ache.” In those individuals we know that their performance is much, much better, right, in the 90s, right? If you’re going to use this test, let’s say, for truck drivers that are crossing one border to another and the prevalence, so, they – these are healthy individuals, they’re fit, they’re able to drive, they come from countries that are unlikely to have big numbers of people infected, that’s when you may see a drop of – you know, into the worrying below 80s, if you want. But in that context, leaving 80 trucks full of very essential commodities, crossing one country to the other, to open economies and leaving 20 truck drivers behind that can be maybe either repeat or get a PCR and confirm that – if they’re truly negative, or positive, sorry, is not such a bad thing, right? Now, let’s say – so, sorry to qualify the question, in terms of context. For people that are sick with symptoms, the likelihood of getting this result incorrect is much lower. Now…
Professor Rosanna Peeling
Yeah, and, Emma, I’d like to say, you know, it’s – we shouldn’t think of molecular and antigen tests as either/or, because I think even in settings where you do have molecular tests, there are times when a rapid result, even though it’s less accurate, would actually give you the kind of action that – public health action that you need to improve our response to the pandemic. For example, in a very busy hospital, when the Outpatients Department is inundated with people with COVID like symptoms and you need to triage them, even if you have a lab onsite, these patients, according to studies that’s been done, could be waiting as much as 20 hours for their molecular test result, because it just takes time. These good tests take time and so, then you have a situation where it’s overcrowded, you may be exposing people who are not infected to those who are infected. Or they’re being moved around and, you know, there’s some studies to show that these patients get, in the 20 hours, get moved around to different spots in the hospital and therefore, actually spreading the infection around the hospital.
The same with care homes for the elderly, when they’re so vulnerable, having a rapid result would be really useful for rapid isolation, you know, and care for those patients. And it’s really, the 80%, it’s not a random 80% that you pick up, it’s not, like, luck of the draw, it’s actually picking out the people with very high viral loads, compared to the 20% that test negative. Those people have low – much lower viral loads and, therefore, may be unlikely to transmit. So, having a rapid triage system, in some cases, even when molecular testing is available, is something to consider and not to say either/or, right?
And then…
Emma Ross
Okay, but you…
Professor Rosanna Peeling
…the other thing that I want to say is that quality of the testing is important. So, we talk about the – lots of about the quality of the test, but if the testing is not done correctly, we’re still not getting good results. So, that’s really…
Emma Ross
Rosanna, can you use both together, both tests together on the same person at the same time, is there any value in that, or have you got to pick between the two?
Dr Sergio Carmona
So, I think that’s an issue of resources, right?
Professor Rosanna Peeling
Yeah.
Dr Sergio Carmona
So, in some countries, I think Singapore has done really well. They have an infrastructure that can use both concurrently, all the positive get quickly confirmed and then, because of those false positive, probably only ten or 12% are really positives, right? And then you reduce that number and, again, it’s an issue, and the time to act is more important, I would say, in those cases. So, the – and the frequency, right? If you’re using these once a week, or twice a week in some key populations, you probably – the idea, overall, as David points out, what is the point of testing? The point, I think, of testing, generally, is to get over this pandemic, take out of the communities those that are positive and likely to transmit to others. The sooner we do that in a close community, let’s say, the sooner it’s over and modelling has shown that timing it trumps inaccuracy, if you want. So, a closed community that yo9u model is more likely to overcome the pandemic if you’re taking out sooner, rather than later, those that are infected and infectious.
Emma Ross
But to Louise’s question, do you envision that these rapid diagnostic tests might get more accurate, do you think it’s going in that direction, or are we stuck with what it’s got?
Dr Sergio Carmona
Yeah, so, again, someone reminded me about HIV and David and Rosanna are veterans to many other pandemics and epidemics. But coming from South Africa, we saw how first, second and third generations of these tests got better and better, how they were – became easier to use and even today, HIV is something – we already have self-testing in HIV. So, we are monitoring that, and we already seen some improvement. It’s amazing, Emma, what could – what was done in just a few months. These kind of developments used to take years in other diseases. So, yeah, my view or impression is it’s, I would say, yes, but Rosanna and David have…
Emma Ross
Okay.
Dr Sergio Carmona
I take it over…
Emma Ross
No, no, I accept – let’s accept that and move onto the next question, so we can get through a few more. Here’s the next most upvoted question, from Dr Annapurna Sharma, “Ethically, what do you think is the difference between, say, a yellow fever vaccination certificate and a COVID-19 vaccination certificate?” David, do you want to take that first?
Professor David Heymann CBE
Yeah, well, yellow fever vaccination is known for many, many years, since the 1930s and it’s known that this vaccination prevents – it’s a sterilising vaccine, it prevents against infection. We don’t know yet what the COVID vaccines are doing. Are they preventing against infection, or are they all only modifying infection, once it occurs and making it so that a disease doesn’t happen? So, we don’t know enough about these vaccines yet to say that a vaccination certificate would be useful, but it certainly is useful in yellow fever, provided it’s not been faked, provided it’s not a counterfeit certificate, which happens, and provided the vaccine that was used has been kept cold until the time it was used.
So, you know, vacc – it’s very important to understand that vaccination certificates will one day, likely, play a role once we understand more about this – these vaccines. And just like for diagnostic tests, there are an incredible number of vaccines that are under development. This has never before happened. It’s usually one vaccine at a time and it takes a long time to get that one vaccine out. So, you know, it’s not possible to give all the answers.
But, Emma, I’d just like to jump back to this question that you asked earlier, because I see there’s still confusion. And this is the question about a rapid test to look for the virus, if I want to go to Christmas dinner with my grandparents. You know, if I’ve been – if I have a positive test, I will certainly not go, that’s clear. It could be that I do have an infection and I wouldn’t go. But if I have a negative test and I’ve been self-isolating myself for the last two weeks, I would still feel confident in going. But if I went to my office Christmas party last week and then tested myself and it was negative, I would not be confident enough in going, because it may be that there hasn’t been enough time between the time I got infected and the test to make that virus visible. So, testing is all about the odds and about a whole series of things in risk assessment.
And just one other thing, countries in Asia are now looking at a testing strategy before flying to see whether or not they want people to fly. And their modelling shows them that they would be will – that if they were doing rapid testing for the virus on each person getting on an aeroplane, they might have 60% decrease in people who got off that plane and went on to get infected. So, they’re willing to accept a risk of 40%, in order that they can, in fact, begin travel onwards, as Rosanna says, to get their economy back.
Emma Ross
So, do you all think that rapid diagnostic tests at airports or connected with airline travel is going to bring us all back to aeroplanes more quickly and get us back to normal in the airline industry, aside from the issue that we can all do Zoom meetings, we don’t need to travel? But as far as confidence in the experience of flying, is testing going to be an important part of that and the way it’s being envisioned to be used, as David just described, is that okay, good idea, misguided, what do you think?
Professor Rosanna Peeling
I think that in terms of using these rapid tests to rule out that a person – you know, to say that the person is negative, I think that the – with the current tests that we have, we can be fairly certain, you know, the negative predicted value of these tests are good. And so, we could be quite confident that they rule out a person that’s infected, you know, and so – but as David says, it all depends on the circumstance, the context within which the test results have to be read. And so, I think that, you know, some airlines are demanding that you show that you have a negative test on boarding and some countries require that you have a negative test on entry into the country and then seven days after, you are supposed to report for another test. And so, these strategies are being developed at the moment and there are different models that show that they could be effective in allowing more people to return to work, to, you know, to open up, you know, different sports events, mass gatherings, etc. But it – we are taking some risks, and there’s never going to be – no test is perfect. So, you know, I think we use them as weapons, as best as we can for the pandemic response and, you know, we need to balance its accuracy with its accessibility and timeliness and costs, you know, the three A’s that I always teach about diagnostics: accuracy, accessibility and affordability. And accessibility includes timeliness and being able to use them well and use them and know that they’re quality assured. Yeah, I think those are the, sort of, you know, big caveats to how you – how different sectors use the tests. But I think it should not be used to – as a condition of employment in terms of, you know, violation of rights and all that. So…
Emma Ross
Sure, sure. There’s one from Toby Bonvoisin and I think this might be for Sergio. “Why were PCR tests widely available so much earlier in the pandemic than antigen tests? How…
Dr Sergio Carmona
Ah, that…
Emma Ross
…can the development of antigen tests be sped up for the next emerging pathogen?”
Dr Sergio Carmona
Very good question. So, again, and this comes from having the – it’s a bit like these new vaccines, right? So, it’s easier to generate a vaccine, like the ones that we – make it into the press, because it’s new technology, right? This is genetic, engineered little piece of RNA that then can produce a protein that mimics the virus, right? The same applies. So, it’s much faster, once the so-called Berlin protocol was released, the sequence of the genome, it’s only been this year, by the way. I mean, it’s – David, remind me, it was January or so that the sequence was known. A couple of weeks later protocols were developed that managed to determine how to amplify the genetic signal and that’s, kind of, the fastest way diagnostics can be developed, right? They – if there’s a bit of – then there was a whole market collapse, the Global North had ability to buy and everyone – every other member state was scrambling for these tests. But we know that those tests need to be run by professionals, and it’s prone to contamination and requires devices.
Now, these new rapid ones that are simpler to use need an antibody to be developed to be made in a recum – in a factory, in a brewery, if you want, right? And to develop those and to find a clone that is good enough to pick up the virus takes time. You can’t buy that time, like you could with the PCR. Now, having done that, WHO and many other organisations, I work closely with Africa CDC, there was urgent need to deploy that PCR, those kind of technologies for genetic testing. Now, once they – and these rapid tests that were produced at scale, right, because that’s another thing, and massive numbers, that they were of good quality and good accuracy, as you pointed out, quickly, we managed to set up studies in Europe and in Latin America to check are they really this good? And as Rosanna said, confirm that the manufacturer claims are indeed true in different settings. Once we knew that, those – that data was made available quickly to WHO and within weeks, these tests became available to many countries.
So, I know it seems like a long time, but in normal days, this would have taken years and it’s just taking a few weeks to months. So, of course, now our big effort is to ensure that these tests become available at scale, that they’re also affordable to many countries that are starting to see these second and third waves, so, yeah, good question.
Emma Ross
Okay, no, well, that was a good question, actually.
Dr Sergio Carmona
Yeah.
Emma Ross
We’ve got time for one, maybe two more. I’m going to pick, actually, this one, it’s from Jill Murray, “Assessing the reliability of diagnostic tests is clearly very complex. Could you comment on whether approved for emergency use only strategy was, in retrospect, a good one, what lessons for the next pandemic?” David, do you want to come in on that one?
Professor David Heymann CBE
Well, yes, I think that, you know, Rosanna and Sergio and I have all been talking about the need to be better prepared to validate new tests when they come onto the market, because the global community is not able to do that rapidly. They have to take the information that’s provided by the testing done by companies, which is reliable, in most instances, but which doesn’t give the variety of different types of testing or types of situation that would be important to use these tests in. And so, those conditions need to be created by collecting what’s called panels of sera from many different people, at many different stages of infection, in order to be able to better validate these tests.
And so, I think that as the global community becomes better prepared, one of those will be, and Rosanna and Sergio will correct me if I’m wrong, will be to have better availability of standardised panels that can be used or collected early on in an outbreak, to be used to validate tests much more rapidly than has been done. Now, that’s called…
Emma Ross
Don’t you mean…
Professor David Heymann CBE
…external…
Emma Ross
…not – so, it wouldn’t have to be an emergency use, it’s done a full round, is that – the question was whether emergency use authorisation’s been a good idea, or…?
Professor David Heymann CBE
They would still be emergency use authorisation, but they would be validated better than they are now. But Rosanna and Sergio will have a better possible…
Emma Ross
Okay. It’s going to have to be…
Professor David Heymann CBE
…comment.
Emma Ross
…the last question, then.
Dr Sergio Carmona
I think it’s, again, about a risk, right? I think WHO and FDA did very well by encouraging the, you know, the development of these tools quickly. We will be very sorry today if we didn’t have WHO Emergency Use Listing, I would say. It’s not, by all means, perfect, but with time, those things can definitely be – it’s a risk strategy that has allowed for manufacturing, developing and use of these tests at scale, so, definitely.
Emma Ross
Okay.
Dr Sergio Carmona
I don’t know, Rosanna, maybe are you in – are we in agreement?
Professor Rosanna Peeling
Yeah, and I said that…
Emma Ross
We’re at time, so I have to wrap up, but if you’re quick, Rosanna, you can squeeze it in.
Professor Rosanna Peeling
Yeah, I think to be better prepared for the next pandemic or epidemic, I think we need a lot more international collaboration to come up with those standardised panels for evaluation very quickly and – so that we could systematically go through the different tests that appear on the market and make sure they’re good. Okay? Oh, have I…?
Emma Ross
Okay, thank you, that was quick. Thanks for that. So, there are a few more questions that all look really interesting, so I’m sorry we couldn’t get to them, but that is all we had time. Some really important considerations have been raised today. So, Sergio and Rosanna, thank you so much for spending your time with us today and…
Dr Sergio Carmona
A pleasure.
Emma Ross
…for your great insight into this really complex world of COVID testing. And thank you all, to everybody else for tuning into this last session for the year. David and I do plan to be picking up again in the New Year, with some new angles on this still very much ongoing pandemic, so, please do look out for any announcement of when we might be starting up again. But thank you both, Rosanna and Sergio, it was…
Dr Sergio Carmona
A pleasure.
Emma Ross
…great to talk to you.
Professor Rosanna Peeling
Thank you.
Emma Ross
Yeah, and just…
Professor Rosanna Peeling
Thank you, thanks.
Professor David Heymann CBE
My thanks as well.
Emma Ross
And, yeah, have a great rest of the day, everyone, thanks.
Dr Sergio Carmona
Goodbye. Thanks for inviting…
Professor Rosanna Peeling
Bye, bye.
Dr Sergio Carmona
…us, bye.
