3. Professor Christopher Brightling

PROFESSOR CHRISTOPHER BRIGHTLING (affirmed).

Questions From Counsel to the Inquiry

Lady Hallett: Mr O’Connor.

Mr O’Connor: Thank you, my Lady.

You are Professor Chris Brightling and Dr Rachael Evans; I think that’s right?

Professor Brightling: Correct.

Mr O’Connor: Between the two of you, you have written for us a report relating to Long Covid; is that right?

Dr Evans: Correct.

Mr O’Connor: We have it on screen. It’s a lengthy document, but we see that on the first page there is a statement which reflects, is this right, your understanding of the duties upon you in writing this report, the duties of an expert witness, and that you understand those duties and that you’ve complied with them, and then both your names, both dated 26 September of this year. Is that right?

Dr Evans: Correct.

Professor Brightling: I do.

Mr O’Connor: Thank you.

Professor Brightling, there is a lengthy account of your career on the second page of the report, I don’t ask that we bring it up. In summary, you’re a professor of respiratory medicine at the University of Leicester; is that right?

Professor Brightling: That’s correct.

Mr O’Connor: You have been a consultant since 2004.

Professor Brightling: Correct.

Mr O’Connor: And you remain a treating consultant physician.

Professor Brightling: Yes.

Mr O’Connor: Of important relevance for us today, you have been considerably involved since 2020 in both studying Long Covid and also treating those who have that condition.

Professor Brightling: That’s correct.

Mr O’Connor: Dr Evans, you are an honorary respiratory consultant physician at the Glenfield Hospital, which is part of the University Hospitals of Leicester NHS Trust.

Dr Evans: Correct.

Mr O’Connor: And you are also an associate professor at the University of Leicester, and with Professor Brightling, as we will hear, you have also been involved in studying Long Covid and also treating those who have developed that condition.

Dr Evans: That’s correct.

Mr O’Connor: Now, I’m going, Professor Brightling and Dr Evans, to take you through various topics which more or less mirror the contents of your report.

You are giving evidence together. It’s very important that we try to avoid overspeaking between the two of you. I know, because I have discussed this with you, that there are various parts of the report that each of you are more familiar with or reflect more fully your experience, so I’m not going to sort of direct my questions to one or the other of you, but perhaps I can invite whichever of you feels most sort of authoritative in that area to address the particular issues, and of course, once whoever that is has done so, if the other one has anything to add then please feel free, but we will take it slowly and try to avoid interrupting each other.

I’m going to start with what is a very general issue, but it forms, if you like, the sort of precursor to considering Long Covid, and that is just the question of: what is a post-viral syndrome? We’ll come to some of the detail around this issue, but my first question perhaps is whether there’s just a simple definition of a post-viral syndrome?

Dr Evans: Well, post-viral syndromes cover a wide group of conditions. There’s always an original insult by a virus, but that virus can affect any part of the body. Sometimes the acute illness is severe, sometimes it can be very, very minor.

The ongoing sequelae of that virus is what we terms the post-viral syndromes, those typical symptoms of fatigue, brain fog, sometimes muscle pain, and a whole constellation of symptoms. They can be multisystem, so meaning they can affect any part of the body, and they can be very variable, so for any particular virus there might be a syndrome for that particular virus which can look very different and last for different lengths of time.

Mr O’Connor: Thank you, Dr Evans. And is it right then, following what you say, that as a result of the variability of the symptoms, these post-viral syndrome conditions can be more difficult to diagnose than other conditions?

Dr Evans: So, yes, because they’re very variable, so you can predict that for any virus you may get a post-viral syndrome, but what exactly that looks like may be very variable.

Mr O’Connor: Yes. But nonetheless, when we are talking about classified post-viral syndromes, there are, as we’ll come to see with Long Covid, understood definitions, and therefore a physician will normally be able to reach a diagnosis?

Dr Evans: Absolutely, they are conditions where you can give what we would call a positive diagnosis. So even though you might not have a specific test that tells you what the syndrome is, that clinical picture, that clinical history can give you the diagnosis.

Mr O’Connor: And you’ve referred, Dr Evans, to some of the symptoms involving fatigue, lasting fatigue. You haven’t yet mentioned chronic fatigue syndrome, but that is a syndrome which occupies much the same area as the one you’ve just been describing, is it not?

Dr Evans: So you can have a post-viral syndrome that’s not necessarily going to lead on to chronic fatigue syndrome, so chronic fatigue syndrome and ME have a very precise definition across – but there are many different definitions for it.

So the CDC have defined chronic fatigue syndrome as that you must have fatigue and that it’s fatigue in response to an activity or a stressor where you wouldn’t expect necessarily someone to be fatigued from that. And then symptoms of something called post-exertional malaise or post-exertional symptom exacerbation where that would infer that the person gets symptoms after an activity or a stressful event or it can be a cognitive stressor.

Then, on top of that, they also have to have unrefreshing sleep. So that’s one definition. And those symptoms then go on for over six months.

Mr O’Connor: All right, that’s very helpful. So would it be right to say that post-viral syndromes can cause chronic fatigue syndrome, but they don’t always?

Dr Evans: That’s right.

Mr O’Connor: And as we’ll come to address in detail, Long Covid has amongst its symptoms fatigue but there are other symptoms which some people suffer which don’t include fatigue?

Dr Evans: That’s correct.

Mr O’Connor: Let me ask you a further question, Dr Evans, a little bit more focused. Can you give us some examples of viruses that have caused these long-term sequelae, the post-viral syndromes?

Dr Evans: Yes. So if we think back to the early part of the pandemic where the coronavirus was mainly causing acute lung injury, that was very similar to other viral pathogens that we’ve seen, the original SARS CoV virus and the MERS pandemic, both of those viruses were respiratory viruses that caused ongoing lung issues, but there can be viruses, such as the Epstein-Barr virus, which we normally think of as causing glandular fever in teenagers, and then there are a proportion of teenagers that go on and develop ongoing fatigue from that.

Mr O’Connor: So that’s glandular fever, but just switching back to SARS and MERS, those of course are both coronaviruses?

Professor Brightling: If I may take that. So SARS-CoV-1 led to an epidemic in 2002 to 2004. The scale was considerably less than SARS-CoV-2, so less than 10,000 people actually were affected, and fewer than 1,000 people died of that. And the best data in terms of the long-term effects came from studies in Hong Kong, so they looked at a relatively small number of 100 individuals, and followed them up, for a year in their initial publication and two years in the subsequent publication, and they found symptoms such as breathlessness and fatigue, but they also it did lung function testing, and when they did that they found that the lung function was impaired, in particular a test which we know goes with – is associated with lung scarring, and that was seen in a quarter of the people with SARS-CoV-1.

So using SARS-CoV-1 as an example really gave us some clarity about the likelihood of what might happen in SARS-CoV-2.

Mr O’Connor: Let me turn to that, then, which is my next topic, which is the question of the foreseeability of long-term sequelae from Covid-19. Perhaps if I can ask the question, at least first of all from the perspective of what was known in very early 2020 as, as we’ve heard, the information started to come out of China about this new virus. Of course we’ve learnt a huge amount since then, but just on the basis of what was known in those early days and weeks in January 2020, was it foreseeable to those of you who understand these things that there might be long-term sequelae from Covid-19?

Professor Brightling: So very early on we were already considering that there was a number of clear areas that needed to be addressed: certainly addressing the acute condition and trying to improve management in the hospital; vaccination to try and then be part of the public health measure; and also then the likelihood of long-term effects.

So this is something that we had recognised very early on and then developed a programme of work, which we then wrote up in the March of 2020. And we were learning things from others as well, so at that time I was also the chair of the Science Council for the European Respiratory Society, so I was getting – I was in regular contact and had a number of conversations with others in China but also particularly in Europe, and obviously in Italy, was already hearing about some of the early things that people were finding after the Covid infection, so it was foreseeable to us before the pandemic, because we were aware of what had happened with SARS-CoV-1, and it was even more apparent early on in the pandemic that this would be a potential problem.

Mr O’Connor: So just to be clear, Professor Brightling, when you say “before the pandemic”, do you mean in 2019, before we’d even heard of any cases, your understanding of SARS-CoV-1 gave you to believe that a further coronavirus similar to it would cause long-term sequelae?

Professor Brightling: Correct. So the SARS-CoV-1 post-viral syndrome data was in the public domain by 2010, and had been presented and discussed at scientific meetings ahead of that. So although the numbers were very small, we were aware of the post SARS-Cov-1 syndrome, as well as the other viruses that Dr Evans has described.

Mr O’Connor: Then I think you’ve explained that as soon as the news started to come in of the developing epidemic, pandemic in China, you swiftly drew the conclusion that there might well be long-term sequelae from that virus?

Professor Brightling: Correct. And we really became very much in an activated stage to then actually write up the protocols then in the March, when it seemed apparent to us that there really needed to be work done and why shouldn’t we be the ones doing it.

Mr O’Connor: When you talk about writing up the protocols, we’ll come to hear more, probably after lunch now, about the study that the two of you were deeply involved with in terms of hospitalised patients of Covid. Was it at that stage that you started planning and moving towards undertaking that study?

Professor Brightling: So the point where we more formally wrote up the protocol was from the middle of March.

Mr O’Connor: Yes.

Just before we leave this topic, you’ve told us, and explained why, when you believed long-term sequelae were certainly foreseeable. That’s a binary issue: are there going to be long-term sequelae or not? At that very early stage, how confident were you able to be about the incidence of these sequelae, of their severity, exactly what form they would take and so on?

Professor Brightling: So there’s two important things to consider there. One is how big a scale the pandemic would be, and certainly we now know really just how huge an effect it’s had on the entire planet. So, first of all, it’s how big is the pandemic, and then it’s what’s the proportion of those that then have subsequent, as we now know it, Long Covid, because of the infection. And neither of those were really known.

So we felt that there was likely to be a problem coming, but we didn’t know the true scale of that until we understood the size of the pandemic and then had early data coming in around the potential prevalence.

Mr O’Connor: Yes, thank you.

I want to move to the next topic, if I may, which is just an overview of the emergence of Long Covid during 2020 and perhaps a little into 2021.

I’ve referred to your study which related to hospitalised patients suffering from Covid, and you describe in your report how the early work and the early understanding of these long-term sequelae was quite sharply focused on those people suffering from Covid who were hospitalised.

Can you give us a little bit more detail on that, please?

Dr Evans: Yes. So, following on from the last line of questioning, the other group that we had information about is patients where they have a very severe lung injury ending in hospital, requiring oxygen and sometimes breathing machines to help them. And people with those conditions, so either acute lung injury or something known as adult respiratory distress syndrome, can, we know from other studies, particularly large studies from Canada showing that those patients can have ongoing consequences for many, many years – both health consequences and consequences for occupation, so the fact that – the SARS-CoV-2 virus, we knew from China quite early on that the predominant illness at that point was very much the acute lung injury, so that was one element to why we were looking at those people that were in hospital.

But there were also some logistical challenges around setting up a research study. So people in hospital had a clear diagnosis from a clinician, even if we didn’t have the testing confirmed right at the beginning. So you had a firm start point and then a follow-up. Scientifically it would have been very difficult at that time, without thought before, because of the lack of testing as well in the community, so it was quite challenging to study that group.

Mr O’Connor: At any rate, that was the cohort that you focused on in setting up this study, which was, we see the acronym, PHOSP-Covid – is that how you refer to it?

Dr Evans: Yes.

Mr O’Connor: It’s in fact the Post-hospitalisation COVID-19 study –

Dr Evans: That’s correct.

Mr O’Connor: – as we say, focusing on this quite sharply defined cohort of really very ill people who have been hospitalised with severe lung symptoms, injury, needing oxygen and so on. And one of the points you make in your report is that people who have undergone an experience like that, particularly if they have been in an ICU unit, may have sort of continuing symptoms, almost just because of the intensity of their treatment in hospital, which is something rather different from the continuing perhaps post-viral syndrome associated with their initial infection; is that right?

Dr Evans: Yes, so there’s a spectrum of problems that somebody in hospital after or because of SARS-CoV-2 will get. That can be, like you’re saying, that people might end up on the intensive care unit where they’re having – they’re needing organ support, so support for their breathing, support for their kidneys, and multiple drugs, and there are things about that illness on intensive care, something that’s often called post-ICU syndrome, which again can last many months, many years, that is well documented. But apart from that, being in hospital, being inactive and unwell for prolonged periods can have other consequences, so on top of also having the potential for post-viral syndromes.

Mr O’Connor: Yes. So all of this, then, is very much focused on those people who were in hospital and who were extremely ill in hospital, but, as you’ve explained, those were the people who you were able to confidently make the subject of the study.

It’s right, though, isn’t it – and I’m going to come to this after lunch – that there was a very different cohort of people in 2020 who, as we now know, were suffering from Long Covid; they may not have had a diagnosis, they may not even have known what was wrong with them, and they weren’t the subject of the study that you were undertaking?

Dr Evans: That is correct.

Mr O’Connor: My Lady, that is a slightly different topic, and I was proposing to turn to it after lunch.

Lady Hallett: Certainly. Thank you very much. I shall return at 2 o’clock. I hope you were warned that we would break over lunch.

Dr Evans: Yes, thank you.

(12.58 pm)

(The short adjournment)

(2.00 pm)

Lady Hallett: Mr O’Connor.

Mr O’Connor: I’m grateful, my Lady.

Professor Brightling, Dr Evans, before lunch I had asked you some questions about that cohort of patients in hospital who you had begun to study in the early months of the pandemic, who were suffering from long-term symptoms.

But then just before we finished, I mentioned that other group of people who were suffering longer symptoms, who in fact turned out to be a much larger group, did they not, in the community? It’s right, isn’t it, that their situation became known largely as a result of their own voicing of their concerns about the symptoms they were suffering?

Dr Evans: Yes, absolutely, there wasn’t the testing in the community at the beginning, and there really wasn’t the recognition of what we now know as Long Covid, and actually the patients really got together as one voice to really advocate for what we know now as Long Covid, indeed actually defined Long Covid, and a number of different charities that now exist that got together in those early months, May and June of 2020.

Mr O’Connor: Some of those groups are of course core participants before this Inquiry, and we’ll be hearing some evidence later this afternoon in relation to them.

As you say, the term “Long Covid” I think was coined by the patient advocates of those groups.

Dr Evans: Absolutely.

Mr O’Connor: Looking back on it, do you think that the NHS or public health authorities could have done more in those early months to have responded to the developing picture relating to Long Covid sufferers in the community?

Dr Evans: So I think with hindsight the answer to that is absolutely yes, that they were left alone with what is a very frightening condition, that they didn’t know what was happening, healthcare professionals weren’t there to support them and the research wasn’t there, and perhaps more could have been done at the start, before the pandemic, to actually prepare for what those post-viral syndromes might have been.

Mr O’Connor: As we know, and as you describe in your report, you’ve just mentioned May and June, but as that year went on, no doubt partly because of the campaigns that we’ll hear more about that were being mounted by those various patient advocacy groups, there was, was there not, more engagement from the National Health and other public health authorities relating to Long Covid?

Dr Evans: Absolutely. So there were clinics started very organically to look after the people post hospital, many clinics across the UK were set up in that fashion, or doctors that had looked after people in acute care were naturally following that group up, but the people with that lived experience of ongoing symptoms for many months were then trying to seek healthcare themselves. And you will see in the report that that was incredibly challenging. But some people then were getting referred into the NHS clinics, so actually clinicians like myself across the UK were becoming more family with this syndrome.

Mr O’Connor: Yes, and NICE, as we will see, and I’ll come back to it, but towards the end of that year, in I think October and December of 2020, issued guidance and also an important definition of the condition.

Dr Evans: Absolutely. And although it was early days and we didn’t know all about Long Covid, it was really important to have that definition and particularly for people with the lived experience to actually have the symptoms that they were suffering from actually recognised.

So those definitions included post-Covid syndrome, where you’ve got ongoing symptoms for many weeks and without another underlying condition. And I spoke about a positive diagnosis earlier and that’s what we as clinicians would do.

Mr O’Connor: I’m going to come on to ask you a few more questions focusing on diagnosis in a little while, but just sticking with the chronology and those events towards the end of 2020, in October, I think it’s on 7 October 2020, NHS England announced what they called a five-point plan relating to Long Covid, did they not?

Dr Evans: That is right.

Mr O’Connor: And it’s been helpfully brought up on the screen. This is how you’ve presented it within your report, and we can see there, if we just look at the points in this plan, first of all:

“New guidance from NICE …”

That’s what we’ve just been talking about, isn’t it?

But the second point:

“An online website of supported self-management called Your Covid Recovery …”

Tell us a little about that.

Dr Evans: Yeah, so that, again, started early in the pandemic and was released, I think, in July of that year, and it was really to help the supported self-management of people. Again, it was rather focused on the post-hospital group to begin with, but through all the advocacy of those patient support groups they did work together and actually make it more acceptable and more appropriate for the whole of the ongoing symptoms after Covid. And that was funded through NHSE and led by Professor Sally Singh at Leicester University.

Mr O’Connor: Point 3, I think you already referred to the development of clinics. You referred to people going seeing their GPs, but the plan seems to have been to move towards designated Long Covid clinics.

Dr Evans: That’s right, so that when people do seek healthcare in the UK through their primary care team that they then have got the option of being referred to a specialist clinic by people that are aware of the syndrome, familiar with it, can talk through all the different problems, and at least help with that supported self-management.

Mr O’Connor: And the fourth point is funding for research. We’ve already touched on your research, which by this stage was well under way, was it not, but there was more research which came a little later and amplified the research that you had started? Is that fair?

Dr Evans: That’s correct, yeah.

Mr O’Connor: Then the last point – I’m sorry.

Dr Evans: Can I just add, and that research call, just so that it’s clear, was for people that had not been hospitalised for their Covid-19. That was the important difference –

Mr O’Connor: So the community –

Dr Evans: Yeah, absolutely.

Mr O’Connor: – cases.

Then the last point, the setting up of something called the NHS-England Long Covid taskforce. Is that something that either of you two were personally involved with?

Dr Evans: Yes. Well, we both had involvement in slightly different ways. There were different workstreams within the Long Covid taskforce, so there were clinicians, academics and people with lived experience. I was involved more closely in the clinical workstream, around the clinic set-up, and Professor Brightling was in the research workstream, and Professor Sally Singh that I’ve mentioned was in the rehabilitation stream.

Mr O’Connor: Thank you. That’s all I wanted to ask about that plan.

The next point is that, perhaps running alongside the development of the five-point plan, in very much the same period, there was engagement from the DHSC itself, and a series of ministerial roundtable meetings which, Professor Brightling, I think you were involved with, starting with a sort of pre-meeting, I think, in the summer, and then a series of more formal meetings starting in the autumn?

Professor Brightling: That’s correct. So the evolution in terms of timing, things were all happening very close together, so you had interactions through reports from the Academy of Medical Sciences and also things that were then presented to SAGE, which I’m sure you might want to come back to shortly, and that really led to then that first meeting which was the end of July which was then chaired by the Secretary of State, which then led a little bit later to then the setting up of the roundtables that were chaired by Lord Bethell. And, as Dr Evans has described, that also included people with lived experience.

Mr O’Connor: Yes.

Professor Brightling: And between those two was actually when that five-point plan was published. The five-point plan was published a week before the start of those regular meetings.

Mr O’Connor: This is all explained in your report, but just to get this out, those roundtables, as you say chaired by Lord Bethell, continued I think for 12, 18 months on a regular basis after that; is that right?

Professor Brightling: Correct, they went into the following year.

Mr O’Connor: As I say, there is a lot more detail in your report about these various initiatives and developments, but would it be fair to say that, possibly from a slow start, as Dr Evans said, towards the end of that year things did gather pace in terms of engaging with the calls from the patient advocates and trying to understand this new condition?

Professor Brightling: Yes, I mean, I think it was – as we’ve already said, I mean, it was slow paced initially, primarily because of the focus of those who have been hospitalised, and then very much it was taken on board that this is clearly a condition that also affects people who had Covid in the community, and then the community calls, as Dr Evans described, then came out at the end of the year. So the main tranche of funding after the initial funding for our study then came very much as a focus around those who had been affected in the community.

Mr O’Connor: Let me go on and ask you more questions about your study, and for these purposes if we could go to page 10 of your report, and it’s the top of that page, we see there the reference to your PHOSP-Covid study. And at the bottom of that paragraph, which has been enlarged on the screen, you summarise the aims of the report: first of all, to determine the long-term sequelae; second, to investigate the longer-term effects of acute and post-discharge treatments, perhaps reminding us that you were focusing entirely on hospitalised patients; and finally, to provide a platform for future studies of emergent symptoms and worsening of pre-existing disease to improve care for current and future patients.

With that in mind, can you give us a brief summary of the course of the study and what it showed at its conclusion?

Professor Brightling: So, as you can see, we really wanted to understand what was the impact, and a lot of our focus was on the group of patients where we had in-clinic assessments, so they were then seen at two time points, approximately five to six months and one year; and what we were interested in is we were interested in how many of those had recovered, so that was a self-reported question – we had a whole series of different patient-reported outcomes, and the way we put this together was, right from the outset, we recognised this is a condition that’s likely to affect multiple organs, as Dr Evans described before lunch, and therefore we would need working groups with different specialists. So we’d actually engaged, through what’s called the translational research collaboration network, which is part of the NIHR biomedical research network, and that allowed us to then have experts across a number of different disciplines, and in so doing we were then able to then collect all of these patient-reported outcomes. As well as that we were able to then do tests, so physiological tests, such as breathing tests and blood tests.

Our main early findings, I’m going to turn to Dr Evans, because Dr Evans was the first author for those papers, around the effects in terms of the proportions recovered and the types of things we found in those patients.

Dr Evans: So we were really quite alarmed by the first few – the results of the first few months, because even though I’d been running clinics, we knew there were a proportion of people that weren’t fully recovered but actually our study showed that it was over 70% of people that were not fully recovered by five to six months, and our one-year data shows that there is very little recovery from six months to one year. It demonstrated the multisystem organ impairment that was involved and obviously the constellation of very difficult symptoms, the impact on occupation and things outside of health, and an impact on health-related quality of life that we would see with other devastating long-term conditions.

Mr O’Connor: So does this bring us back to the point we were discussing before lunch, that although you were reasonably confident once you knew about the virus that there would be long-term sequelae, you didn’t know how bad they would be and when you found out it was a surprise to you?

Dr Evans: Absolutely, and really, really showed the need for absolute proactive healthcare for this group.

Professor Brightling: But it gave us some clues. So although we were somewhat surprised and we were also very concerned about the scale of the problem, it also gave us some clues about what to do next. So we then had clues around the way different groups of symptoms came together, and we also found that there were certain measurements in the blood, particularly those related to inflammation, that could identify a group of patients that might then be – might be actually open to a potential intervention. And then we’ve moved on to then developing an intervention study that Dr Evans leads, which will be starting very soon, which then has a target where we know what the likely mechanism is in that group. So it’s been very revealing, so that’s gone right through to step 3.

Mr O’Connor: Yes. Just going back to the point we’ve mentioned more than once about the focus of this study on hospitalised patients, of course from the chronology we’ve discussed, as the study was really getting going that was very much the time that you were realising that there were these other community patients. Did you consider at that stage expanding the study so that you could include those patients in the work as well as those in hospital?

Professor Brightling: So, we did. So we applied – so in that first round of funding we’ve described that was focused on people who had been affected in the community, we had as part of that, led by Professor Paul Little from Southampton, worked very closely with him, and a consortium, to put in a similar design study which would build on the experience from PHOSP. But that wasn’t one of the studies that was then supported.

Mr O’Connor: You mean not funded?

Professor Brightling: Not funded.

Mr O’Connor: Right. I’m going to move on in a moment but, just to be clear, we have focused on this study of course because it was the first and the study that you were both deeply involved with, but we do know, don’t we, we saw the point on the action plan, that funding did become available and there are a range of other studies that were ongoing from sort of late 2020 and over for the rest of the pandemic; is that right?

Dr Evans: The funding I think started February 2021, so it was really a year after those first people in February/March 2020 had first got Covid and then got their symptoms.

Mr O’Connor: Does that perhaps teach us a lesson about future pandemics? There are such things, I know, as hibernating studies, and what those are, as I understand it, is, as it were, a study that is prepared in advance, for example, of a pandemic in rather neutral terms, but is then sort of on the blocks and ready to go. And so had such a study been hibernating in early 2020, it would have been much quicker and easier for you to have, as it were, brought it to life, and you could have then hit the ground running and it would have been a much more effective exercise in the last pandemic?

Dr Evans: Absolutely, and we would have needed that wide-scale testing much earlier in order to do that, because in the study of the disease, if you don’t have that first marker of when the infection happened, it’s very difficult or impossible to study. So you need both, you need the hibernating study and then the appropriate testing to be set up at scale.

Professor Brightling: Good to show the real value of that, if I may. So the ISARIC study, which I’m sure you may have talked about here already, which was the observational study of patients who were admitted into hospital with Covid-19, was a hibernating study, and that meant that data was then feeding through into decision-making really early, so if there had been a parallel arm that had been hibernating, then it could have gone alongside the activity of the ISARIC study, and we certainly would recommend that for future pandemic preparedness.

Mr O’Connor: Are, to your knowledge, plans being made or have they been made for hibernating studies relating to post-viral syndromes in relation to a future pandemic?

Professor Brightling: So we’re not aware that that’s been formalised but it’s something that we’re actually part of developing ourselves, and we will then clearly share that with the appropriate people in government.

Mr O’Connor: Thank you.

Let’s move on. I want to ask you just a few more detailed questions about Long Covid itself, starting with diagnosis. We’ve touched on the NICE definition that was provided back in December 2020. Perhaps if we could call that up, it’s quoted in your report –

Dr Evans: Section 1.6.

Mr O’Connor: Yes, thank you very much. So it’s paragraph 1.6, page 6 of the report.

Lady Hallett: Do you know it off by heart?

Dr Evans: I don’t, but I know that page.

Mr O’Connor: So it’s the bottom paragraph, and, Dr Evans, we need to look, don’t we, about six lines up from the bottom, do we see on the right-hand side there is a sentence starting “Post-Covid-19 syndrome is defined”, that was the NICE definition provided in December 2020, was it not? And before we look at it, is it right that that has become a sort of accepted definition that’s used certainly in this country?

Dr Evans: In this country, absolutely. And then the WHO developed, through a consortium, and a Delphi process, which means getting lots of experts and people with lived experience together, came up with a definition of post-Covid condition, which is also given in that section, and they’re very similar. So people have to have experienced ongoing symptoms for 12 weeks, and, importantly, another condition, another explanation has to be excluded. But you can still make that diagnosis with the positive clinical findings.

Mr O’Connor: Right. Was that the WHO definition or the NICE definition that you were summarising there?

Dr Evans: So –

Mr O’Connor: They’re very similar.

Dr Evans: They’re very similar.

Mr O’Connor: Let’s just look at the language on the page:

“Post-Covid syndrome is defined as signs and symptoms that develop during or after an infection consistent with Covid-19 …”

One.

Two:

“… continue for more than 12 weeks …”

Three:

“… not explained by an alternative diagnosis.”

And that would be the definition that physicans up and down the country would be using when they were seeing patients?

Dr Evans: Absolutely. But we also use the language “Long Covid” because it’s a patient-derived term and we have kept that.

Mr O’Connor: Yes. Now, the next – well, there’s no test, is there, for example, a blood test or any other test of that nature, that can be done to determine one way or another whether someone has Long Covid; is that right?

Dr Evans: That’s correct.

Mr O’Connor: So if a doctor is diagnosing Long Covid, he or she simply has to go on the wording that we see in front of us and make a decision for themselves about whether the patient meets that definition?

Dr Evans: That’s correct.

Mr O’Connor: Is there anything particularly unusual about having to make a diagnosis as a doctor without a piece of science that tells us definitively one way or the other what the answer is?

Dr Evans: So, no, there’s nothing unusual about that. Indeed, if we go back in time a few decades, that’s how medicine started. We are fortunate now that for many conditions you do have a diagnostic test that helps us confirm a diagnosis. But actually all diagnoses are mainly based predominantly on people’s symptoms and then the investigations support that.

Mr O’Connor: So the fact that there isn’t a test that can be done and a print-out proving the answer doesn’t make it any less of an illness and it provides no grounds for scepticism about the existence of the illness?

Dr Evans: Definitely not.

Mr O’Connor: You’re very clear about that. You refer in your report, at least in the early stages, to a certain amount of scepticism even from doctors, the medical professionals, about Long Covid.

Dr Evans: Sadly that’s correct, yes. And we heard that actually largely through the qualitative work. Qualitative research interviews people and gets their experience. It’s very scientific, it’s recorded, you have trained professionals at knowing how to extrapolate things out of those interviews. And it came really very loud and clear, both when we’re speaking to the patient support groups but also in the research itself, that they were finding it difficult to get believed and difficult to access appropriate healthcare.

Mr O’Connor: But in your view at any rate such scepticism is completely misplaced?

Dr Evans: Yes.

Mr O’Connor: And physicians should simply diagnose according to this definition on the basis of what they see before them and what the patients tell them?

Dr Evans: Yes. And I would say that primary care have a difficult time, and obviously that definition only – because they look after everything, that definition only came about towards the end of the year.

Mr O’Connor: Yes.

Dr Evans: But yes, there isn’t a place for scepticism.

Mr O’Connor: Let me turn if I may and ask you something about the symptoms of Long Covid. It’s something we’ve already heard some evidence about, but if we go to page 12 of your report, please, at the top, at the very top we see paragraph 1.14, you say:

“Long Covid is frequently characterised by symptoms of fatigue, breathlessness, brain-fog, joint and muscle pain …”

Pausing there, do we take it that those are perhaps the most common symptoms that are found?

Dr Evans: Yes.

Mr O’Connor: But you then go on to say:

“… but over 200 symptoms have been reported.”

Does that take us back to the point you were making, Dr Evans, at the start, about all or at least perhaps many post-viral syndromes, which is that by their definition the symptoms can be very variable?

Dr Evans: Absolutely, and the way people express their symptoms can also be very variable.

Mr O’Connor: Further down the page, you talk about “clusters of symptoms”. Is that a feature of Long Covid?

Dr Evans: It is, and by “clusters” we, researchers, tend to be discussing that in terms of a mathematical model to actually group those symptoms together, but it does look like there are certain symptoms that group together, which Professor Brightling also briefly mentioned earlier.

Mr O’Connor: Yes.

Just moving on, if I may, then, the related question of incidence, in other words who you find gets Long Covid. I’m going to ask you about children in a moment, but if I can talk about the adult population first, and for these purposes if we can go to page 19 of your report, and it’s at the very bottom there, the last two lines, you refer to the fact that “any adult is at risk of developing Long Covid”.

Dr Evans: That’s right. That’s an important public health message, that even though we have people that might be more at risk, that actually anyone can develop Long Covid. So anyone that’s contracting the infection can end up unfortunately with this very prolonged illness.

Mr O’Connor: You then go on to say that those who perhaps are at greater risk, shown by the statistics, are people of middle age, people who are female sex, obese, lower socioeconomic status with bring existing comorbidities, those are the groups that you refer to as being more likely to develop Long Covid.

Dr Evans: That’s right, and that’s been shown in multiple different studies, which actually then supports that there is something more robust about that when you’ve got it in – you know, a good handful of studies have all shown the same things.

Mr O’Connor: We know that for Covid itself certainly people who tend to develop worse symptoms of Covid, it tends to be – there’s a bias the other way, in the sense that it’s men who the statistics show have more worse symptoms. Is there any understanding at this stage as to why women seem to be more at risk of developing Long Covid?

Professor Brightling: So if I go back to the acute setting, so men are more likely to have acute Covid that leads into more severe disease and are – those who are older are also more affected, and there is a concept around immune senescence and there is also an increased inflammatory response in men compared to women, so to some of this hyperinflammatory effect that might then lead on to the acute lung injury. It’s important to remember again that you can be of either sex and you can be of any age, but it is more common in those who are men and older.

In Long Covid, as you said, the demographics are different and the demographics are actually more similar to what we would see in things like autoimmune conditions such as rheumatoid arthritis, so this has led us to then consider whether there may be an ongoing inflammatory response and possibly an immune-mediated response that is then affecting this group.

Mr O’Connor: It’s apparent from what you say perhaps two things. First of all, although it’s the acute Covid that triggers Long Covid, they are actually really quite different conditions and therefore these different profiles can be readily explained. But secondly, as we’ve heard from other witnesses, it’s still very early days in understanding Long Covid and it may be that in months or years’ time you understand these matters better?

Professor Brightling: It’s extremely likely that there is more than one mechanism that’s actually driving Long Covid, and one of the things that we’re working very hard at is to try to understand what are those underlying drivers. So I mentioned a little bit earlier about one of the groups that have this persistent inflammation, and this is really critical because then that could lead us on to more of what we would think of as a precision medicine approach, where we would have then have diagnostics that then could start to pick up what might be driving your type of Long Covid, and then most importantly then actually lead on to different treatment strategies for different people.

Mr O’Connor: I said I would come back to children, we have been talking about the adult population, you explain in your report that Long Covid manifests rather differently in children. Are you able to sort of summarise the position in that regard?

Professor Brightling: So in children it’s less common for them to have severe disease, so fewer children then were admitted into hospital. In terms of the prevalence of Long Covid, it’s more common in adults than it is in children, but the prevalence estimates, or in the most recent estimates since the vaccine, would still suggest that it’s in the region of 5% in adults and 1% in children. So although the number of children are considerably fewer than adults that’s still a substantial proportion when you’re then thinking about your own children or other family members. It’s really important to those children and their parents.Yes. And as we’ve heard, not least in the impact video that was shown at the very start of our hearings, there are some children who very sadly suffer from very serious long-term symptoms from Long Covid.

Dr Evans: That’s correct, yeah, sadly.

Mr O’Connor: I’d like to move on, if I may.

Professor, you mentioned this earlier, that I might come back and ask you a few more questions about SAGE and the interaction between SAGE and issues of Long Covid.

Within your report, and of course it’s – we will be publishing it on the Inquiry website for people to read in due course, there is a chapter in your report where you review quite carefully the SAGE minutes, which of course have already been published, and you chart how SAGE during the pandemic referred to Long Covid, kept in touch with the developing understanding of the condition, and on one occasion, I think in 2021, commissioned some further work relating – a report relating to SAGE.

You of course weren’t on – neither of you sat on SAGE. We have heard from two people who were sat on SAGE or associated with it, both Professor Khunti and Professor Medley, that perhaps one of the limiting factors for SAGE during the pandemic with regard to Long Covid was the very fact that so little was understood about Long Covid. That’s, in general terms, a view they’ve expressed.

I’d like to ask you – perhaps, Professor Brightling, you on this occasion – whether you, having reviewed the SAGE minutes and your understanding of the position at the time, think that SAGE might have done more during the pandemic to understand Long Covid or to give advice to policymakers about the risks that it posed?

Professor Brightling: So SAGE did acknowledge very early on in very early meetings that the duration of symptoms after the acute Covid was very variable. They highlighted at the end of April that there was a need to look at the – particularly the post hospitalisation group at that time and asked Professor Calum Semple, who is on SAGE but also was one of the principal investigators of ISARIC, to then look at the consequences in the ISARIC population.

There was also an Academy of Medical Sciences report that I was part of that was then presented to SAGE in the July and endorsed, and this was preparing for the winter, the challenging winter, and that included a section on post-Covid conditions.

However, after that, there really was very little until coming into early 2021 when the early reports were coming through from ONS and then the report from Calum Semple, and also then the report from PHOSP-Covid, which all happened in the March, and that led to the commissioned report that you referred to that was then presented in the July.

So although there’s a chronology of certain points where they were reflecting and going back to what we now know as Long Covid, there was such a focus at the beginning of the acute disease and the move towards accelerating the vaccine programme that it’s clear that the amount of the time spent in SAGE to the long-term consequences, certainly by reflecting on the minutes, not having been in the meetings, the minutes do suggest that there was really very little time spent on thinking about the long-term consequences until coming into 2021.

Again, coming back to this idea of hibernating studies and thinking about preparedness, if they’d had data earlier then the discussions could have been considered earlier, and they also would have been able to have had reports coming into SAGE very early on of progress of those studies and what was being found and how do you then develop clinical services and plans for future treatments.

So I think there was an opportunity missed in terms of timing because of the focus, and quite rightly a focus, on the acute episode and the vaccine, but then as a consequence not really very much time was spent on Long Covid.

Mr O’Connor: So in terms of looking to the future, does that bring us back to, first of all, the need, as you say, to set up these hibernating studies which would be ready to address long-term sequelae of any future pandemic?

Professor Brightling: Yes, and a clear plan not only for the hibernating studies but how those hibernating studies then actually inform clinical practice and then inform potential treatments.

Mr O’Connor: Yes. Thank you.

Lastly, Professor and Dr Evans, I want to ask you just a few questions about understanding of Long Covid at the centre of government. For these purposes I just need to show you a few documents. First of all, could we have on screen, please, INQ000251916.

Now, this is a note, we haven’t, as an Inquiry, seen this before, but I’m sure we will look at it again. We can see in fact from the last page – perhaps if we could just look at the last page now. Yes, thank you.

So it’s three pages long. It’s a note by Chris Whitty, the Chief Medical Officer, it’s dated 31 May 2021. We may have seen, if we go back to the first page, it’s addressed to the private secretary to the Prime Minister, and it is, as the title suggests, a short note describing his understanding of Long Covid as at May 2021.

As I say, I’m sure we will look at this document as an Inquiry again. I know you’ve read it. Can I simply ask whether you regard that as a fair and a comprehensive account of the state of knowledge about Long Covid on the date that it was written?

Professor Brightling: Yes. Yes, it is. It would have also been a fair statement a few months before it was written as well.

Mr O’Connor: Yes, and we will see a little more about how this note came to be written with future witnesses.

That was all I wanted to ask about that document, thank you.

The other two documents I’m going to show you both relate to the Prime Minister, Boris Johnson, and they reflect his views about Long Covid. First of all, as we will see, in October 2020, and then some months later in February 2021.

So just to remind ourselves of the chronology that we’ve already been through, it was late 2020, was it not, when we were talking about the NICE guidelines, the roundtable meetings at the Department of Health, and those other sort of innovations towards the end of that year?

So, first of all, let’s have a look – I see it’s already on the screen – at this box note [INQ000251910]. You can see that’s actually dated 9 October and it’s a note to the Prime Minister about various matters that were arising that week.

If we can go to page 9, please, we can see that point 25 on this list is headed “Long COVID review”, and in fact it does refer to one of the things that Lord Bethell was engaged with at the time, a report that was being prepared, and we see amongst other things a list of the symptoms very similar to the list that we have just been discussing.

But we see that the Prime Minister against that wrote the words:

“Bollocks. This is Gulf War syndrome stuff.”

Before I ask for your comment on that, let’s look at the other document as well.

So if we can now go to document INQ000214216, please. In fact, if we could just – sorry, just give me a moment.

(Pause)

Mr O’Connor: Could we just go to the page before that one, please.

What we see at the very bottom of that page is we see the date, which is 21 February. Do you see that? In fact it’s after midnight, and a message from Boris Johnson on this, this is a WhatsApp. So if we now go on to the next page [page 52/75], there is a series of listed points he makes, and it’s point number – yes, so if we go down a bit. It’s point number 30, so the last point he makes:

“do we really believe in long covid? why can’t we hedge it more? I bet it is complete gulf war syndrome stuff.”

So two comments, one in October 2020, the other in February 2021, of a similar character.

What’s your reaction, having been involved in Long Covid at that time, to those views expressed by the Prime Minister? Perhaps I’ll ask you first, Professor.

Professor Brightling: So the timing of the first document was the week after the release of the five-point plan, and the same week that the roundtable was – actually met with Lord Bethell, with people with lived experience and with academics, including ourselves.

So what was written there was accurate, it was an accurate description of the activity, it was an accurate description of the problem.

I’ve seen this document a couple of times now over the last couple of weeks, and I feel exactly the same, it’s – I’m deeply saddened and extremely angry at the same time. There are people in this room, there are people who are watching, who have either suffered with Long Covid themselves or their loved ones had Long Covid, and I would be surprised if there are people in this room who do not at least know somebody who has had Long Covid.

So to – I mean, I’m not even quite sure what he means. Does he mean bollocks to the science? Well, that’s clearly wrong because the science was already quite compelling that this was a problem. Is it bollocks to the patients, because he actually didn’t really feel that they deserved a voice? And then to have that view sustained right through to the beginning of the year in suggesting that this was something that could be continued to be ignored.

I mean, it’s just … out of all the things that we see, it’s yet another unbelievable thing that happened, and what I don’t know, clearly, is – we don’t know how much this influenced the activity from government and what government then did. But you would expect, if the Prime Minister’s view was such, it may well have had an influence on other people in government.

And I know, Rachael, you feel very strongly as well about it.

Mr O’Connor: Dr Evans?

Dr Evans: Yeah, I mean, absolutely, it’s shocking and just beyond disappointing, and I still feel very emotive when you see it, because obviously we’ve got people here, as Chris has said, that are living through this absolutely dreadful illness. And there is some distrust, we’ve already heard that some clinicians weren’t believing them, but to see that your own Prime Minister has written something like that, I just can’t – yeah, can’t begin to think how people living through it feel.

And actually as clinicians and researchers, we were already feeding back very clear descriptions of what this illness looked like, even if we didn’t know exactly what was causing it and all the rest of it, it was a very real and is a very real phenomenon.

Mr O’Connor: Thank you very much, Dr Evans, Professor Brightling. Those are all the questions we have for you. There aren’t any CPs questions.

Lady Hallett: Thank you, Mr O’Connor.

Thank you both very much indeed, not only for the research and the treatment that you do, but for being an advocate, for getting recognition for what is obviously a dreadful condition. So thank you for all that you’ve done. Thank you for your help.

(The witnesses withdrew)

Mr O’Connor: My Lady, we have one further witness this afternoon, and that is Ondine Sherwood.