The early days of uncertainty and unease

Early alerts to the outbreak in Wuhan

For many people who were plugged into the world of microbiology and infectious disease, the arrival of a new respiratory virus did not come as a surprise. What was a shock was the scale and speed with which it spread. This was no less the case for COG-UK participants, a number of whom first heard the news of the new mysterious pneumonia-like illness in Wuhan via posts on Twitter and other social media channels.

One person to hear about it early on was Dr Joshua Quick, a bioinformatician at the forefront of developing a rapid genomic surveillance system to use in remote and resource-limited locations to sequence samples in the event of an emerging epidemic. He remembers discussing the outbreak in Wuhan at some length with his collaborators Professors Nick Loman and Ian Goodfellow in December 2019 while they were conducting field work on the Ebola virus in Kinshasa, the capital of the Democratic Republic of Congo. At that moment, he says there wasn't a great deal of information out there but he definitely remembers ‘a sense of anticipation’ (Quick transcript).

Another person alerted to the situation early on was Professor David Robertson, the head of the bioinformatics group at the University of Glasgow’s Centre for Virus Research. He remembers seeing a few tweets about a potentially new virus in Wuhan around the 31st of December 2019. For him this was not unusual because, as he says, ‘If you're on ProMed or on Twitter, these kinds of things are going on all the time.’ Launched in 1994, ProMed (Program for Monitoring Emerging Diseases) provides the largest online reporting of infectious disease outbreaks. The situation rapidly changed once Eddie Holmes and Andrew Rambaut posted the first SARS-CoV-2 genome on Virological. Released on the 11th of January, a Friday night, Robertson and his colleagues immediately downloaded it to start analysing it the next day. As Robertson points out ‘when you do bioinformatics, you can work anytime, it never stops. [laughter]’ (Robertson transcript).

Just as Robertson was beginning to pick up that something was happening on Twitter, so too was Professor Emma Thomson, an expert in viral infectious diseases based at the University of Glasgow. She first learnt about it from a tweet put out by Professor Rambaut in January 2020 while she was in Uganda looking for emerging viruses. She was struck by the fact that his tweet mentioned that the cases in Wuhan looked ‘an awful lot like SARS [severe acute respiratory syndrome]’. As she says, ‘I remember thinking it’s very early to sort of jump to that conclusion, but I guess with the experience that he has, I'm probably 10 years behind him or something. I thought, ‘Oh, that looks alarming, but it's not going to definitely be another emerging virus’ (Thomson transcript).

Similar thoughts went through the mind of Dr Peter Muir, a clinical scientist based at a Public Health of England laboratory in Bristol. He remembers hearing a news report of a cluster of undiagnosed cases of pneumonia in Wuhan around Christmas Eve 2019 or New Years Eve. As he admits, ‘To be honest, we didn't think too much of it. We immediately thought about a SARS type event. But of course the previous SARS type event didn't become a global pandemic, so that wasn't really on the horizon’ (Muir transcript). The same reaction was experienced by Verity Hill, who was modelling the spread of Ebola in Sierra Leone as part of her PhD work under Rambaut at Edinburgh University. She remembers ‘I actually saw a tweet about it as I was getting ready for a New Year's Eve party. At that stage, the Chinese authorities had reported it to the WHO [World Health Organisation] as a cluster of atypical pneumonia, so that was the first I heard of it, but I didn't necessarily think anything of it because these things happen all the time. So I was just like, “Oh, that's not great, I hope everything's okay”' (Hill transcript).

Elsewhere, Joanne Watkins, a senior biomedical scientist based in Wales, also got the news early. As she explains, ‘At Public Health Wales we have an emerging pathogens service, so we've always got our ear to the ground and watching, and we've got various different people represented on various different forums etc. We’re aware of what's going on around the world and whether or not we need to have some sort of response to it. So we were pretty much aware and watching from December in 2019, just with interest as it's an area of interest anyway because the flu always seems to start in that area and comes round, so it is a spot that we all look at… Then obviously, you've got MERS [Middle East respiratory syndrome] and SARS which because of their severity are always a watchpoint. We've got a lot of the coronaviruses now in what qualifies as our usual respiratory season. So we’re aware of it and we just keep our eye out for these things’ (Watkins transcript).

While many COG-UK members were concerned about the news coming out of Wuhan, the issue initially felt quite remote. This sentiment is captured in the words of Dr Nicholas Ellaby, a bioinformatician based at Public Health England who heard about the outbreak in Wuhan in early January 2020 from various news sources. At first, he was not on high alert because as he says ‘we had MERS, and we had Zika, and they were always quite exotic outbreaks [so] never really touched home.’ At the time he thought ‘it sounds a bit difficult for China to deal with, but I’m sure it’ll be fine’ (Ellaby transcript). Dr James Shepherd, a clinician who was working on a PhD on emerging viruses with Thomson at the Centre for Virus Research in Glasgow also had similar thoughts. He remembers briefly looking at an email about pneumonia in China around New Year 2019 from ProMed but not paying it much attention because he got a lot of such emails. While the email left an impression on his radar, he ‘had lots of other stuff going on so I wasn't fully focused on it’ (Shepherd transcript).

Likewise, Dr Ian Harrison, an expert in genomics of respiratory viruses who worked at PHE during the pandemic, says that in the very early days when he saw news of the virus on ProMed and other channels that ‘like lots of people because I wasn't working directly on it at that time, my ears didn't prick up until a bit later on when it started becoming apparent that actually it was really taking hold and becoming something quite significant.’ He points out, ‘What you need to be aware about is that we have H5 and H7 outbreaks of influenza in farms and in livestock quite regularly, and although coronavirus is a less common there are small flare-ups, which normally are detected and dealt with and don't go on to become a full pandemic’ (Harrison transcript).

For infectious disease experts one of the key challenges they faced was determining the extent to which the new disease might tip into becoming a global phenomenon. This is succinctly outlined by Dr Emma Hodcroft, a British-American molecular epidemiologist specialising in viruses based at the University of Bern. She recalls, ‘It's very possible that I saw some kind of minor headline about it first, but it's not unusual that viruses move between people and it's often hard to judge from a news article. It's always of interest to somebody, but is this of a wider interest, or is this something small?…certainly at the very beginning, I was pretty happy to keep my distance. I hadn't worked on coronaviruses historically, and it seemed like there were plenty of very great scientists that were focusing on this. So for me, it was like, okay, very interesting, glad the right people are paying attention, back to my work in my little corner of the world. But over the course of December 2019 and January 2020, it started to look more and more like this was something that was going to be much bigger than just a handful of scientists studying a few sequences that then disappear or not really spread’ (Hodcroft transcript).

Where the pandemic quickly struck a chord was with people with connections to where it initially unfolded. For example, Dr Louise Aigrain, then head of Research Operations at the Wellcome Sanger Institute, says the reality of the situation in Wuhan really hit home after she spoke to a good friend who worked with Huawei whose Chinese colleagues were being quarantined (Aigrain transcript). Early on it also concerned Dr Andrew Jermy, who subsequently led COG-UK’s communications team. Part of the reason was that a few years before he had worked in China with people at the University of Wuhan. When he started seeing pictures of the outbreak in late December and early January, he messaged a few people he knew there to say ‘“I hope everything's okay”’. This meant that by the time that the cases started to come into the UK, it did not come as a surprise to him (Jermy transcript). Another one for whom the news very quickly became very real was Dr Alesandro Carabelli who led the COG-UK working group around mutations. He recalls: ‘At the beginning of the pandemic there were images from my city [Bergamo] in Italy where the army was carrying the coffins of people who died… It was one of the first cities and towns which were hit by the virus. That definitely had a huge impact on me. Also because I knew people who got the virus, and they went to the hospital…. So I felt it was really personal’ (Carabelli transcript).

Figure 2.1: Bodies of coronavirus victims in Bergamo, Italy, unloaded upon arrival at a cemetery in Ferrara, where they will be cremated. Date: March 21 2020. Credit: Massimo Paolone/Lapresse Via Ap, STAT News.

Scale and seriousness of new disease begins to hit home

It did not take long for the shock of what was happening to begin to sink in even amongst those with no direct contacts with Wuhan. Anthony Underwood, who was head of translational and operational bioinformatics at Oxford University, first realised the scale and seriousness of the problem when he watched TV images from Wuhan. As he says, ‘At that time we didn't realise it was going to be a pandemic, we just thought here's this really horrible thing going on in a city in China. It looked awful and almost apocalyptic in terms of the lockdown they had, the empty streets…. What was particularly shocking, I think, was the way it had an impact on younger people. There were people in their twenties and thirties and it wasn't sure whether they were going to live or die at that stage. That was really shocking, because I suppose in the West, particularly, we're sort of cushioned from death. We think of death being mostly in the elderly, and the occasional unfortunate person. Whereas of course the reality in many countries is that death happens all the time. It's something that people have to live with, with infectious disease and other things.’ He continued, ‘I still have very clear pictures in my head about the early stuff in Italy with people being wheeled into ambulances and body bags and things like that. I still remember … seeing those pictures and knowing that it was going to be just a matter of time before it came to the UK, then understanding that it's pretty certain that we will be involved in some way with that‘ (Underwood transcript).

Dr Sharon Glaysher, a biomedical scientist based at Portsmouth Hospitals University NHS’s Trust’s Research Laboratory, also remembers the power of watching the outbreak in Wuhan on the news. Based on her background she immediately began thinking ‘How long has this virus been out there undetected, and how far then is it likely to have spread? How is that going to impact us moving forward?' Based on local travel and international travel she understood how 'quickly respiratory viruses can spread.’ She was ‘also thinking that if it's already made the news, what's actually happening locally? Developments happened throughout the pandemic so quickly, news reports were often behind the time’ (Glaysher transcript).

Effect starts to be felt at clinical level in the UK

Some of the first to feel the impact on the ground in the UK were infectious disease clinicians seeing patients in hospitals. This included Dr Thushan de Silva, based at Sheffield Teaching Hospital which is one of the five hospitals in the UK assigned to treat patients with airborne high consequence infectious diseases (HCID) (Gov UK April 2021). He was part of the team that took care of the first few UK nationals who had acquired SARS-CoV-2 in and around China. This happened around February 2020. For de Silva this was when the pandemic started ‘becoming more real in terms of UK impact’. He points out that at that moment community outbreaks were not yet widespread in the UK, so the hospital was isolating anyone that came in and trying to prevent onward transmission. ‘It took a while before suddenly we realised that actually we had to be in a mitigation phase rather than preventing things from spreading’ (de Silva transcript).

Figure 2.2: Sign posted up at Church View Medical Practice, 15 March 2020, Credit: Church View Medical Practice.

Dr Dinesh Aggarwal, a clinical registrar, also saw a similar approach adopted at the Royal Free Hospital in London, which, like Sheffield, was a HCID centre so received some of the first COVID-19 patients in the country. He was asked to come on to the Infectious Diseases section with some other registrars to support the service. As he says, it was like a ‘sudden call to arms’ because the hospital suddenly had to provide ‘a 24-hour service to ensure that if anyone was coming in at the time with what was suspected to be the Wuhan virus … was dealt with by an infectious diseases registrar.’ Being classified as one of the highest category infectious diseases, Aggarwal was highly conscious of the ‘responsibility for making sure that’ the COVID-19 cases were ‘contained’. An entire ward he says had to be converted into ‘a clean high consequence diseases ward, where you had to wear the full PPE, and every patient required numerous bloods and tests to make sure that we were understanding what's going on with them, but also the disease itself.’ He also comments on how quickly the situation changed. ‘Not long after, maybe three or four weeks into my time at the Royal Free, the illness went from something that seemed to be relatively contained, to something that was obviously very widespread. And our role changed quite quickly from being individuals who were trying to directly deal with every case, to trying to be a presence within the hospital and to lead our own team to help ensure that we could support the hospital in just the volume of patients who are coming in’ (Aggarwal transcript) .

Aggarwal’s interview highlights how much COVID-19 was a new experience for everyone. While it was obvious that it affected the respiratory system, he and his colleagues were surprised by the type of breathlessness they were witnessing. What struck him was the number of elderly patients whose oxygen saturations were very low despite not reporting any breathlessness. For him, that was ‘something which normally happens maybe on a night on call, or an evening on call. In that situation you get one or two patients like that and it becomes a big team effort to ensure that the patient is okay.’ But now ‘there was one patient after the other who was in that position. And that was quite overwhelming.’ Adding to the pressure was the fact that because COVID-19 was a new illness they did not have any therapies at their fingertips. The only thing Aggarwal says medics could do at that point was to ensure ‘that the patient was supported with oxygen therapy’ and ‘to make sure escalation plans were in place in terms of them going to ITU’ and reassuring the patients. A lot of their work also involved supporting the families of the patients, which was especially difficult because they were not allowed to visit. As Aggarwal explains, ‘I found it personally quite difficult to take on board that there would be people who were very unwell in hospital, and unfortunately, because of the nature of the virus and how little we knew about it at the time … as a necessity you couldn't allow family members to interact with their very unwell siblings or partners or parents’ (Aggarwal transcript).

Growing sense of urgency and foreboding

By late February the reality of COVID-19 was not only just being felt within hospitals. Its repercussions were beginning to dawn on society as a whole. This was reinforced by the fact that on 23 February 2020 the Italian government decided to lock down several towns in the north of the country to try and contain the outbreak of COVID-19. In addition, several countries were imposing new border or travel controls. The sense of urgency was underlined by the fact that Italy had detected an explosion of 150 cases from fewer than five known cases just three days before. As The New York Times pointed out, the rapid spread of the virus within Italy ‘shattered the sense of safety and distance that much of the continent had felt in recent months even as the virus has infected more than 78,000 worldwide and killed more than 2,400, nearly all in China’ (Horowitz).

Several of the interviews with COG-UK participants reflect the anxiety people were starting to feel at that time. For example, Tim Cutts, then head of scientific computing at the Wellcome Sanger Institute recalls the sombre atmosphere he encountered at a genomics conference he attended around that time. As he says, ‘I don't remember people going, “Oh, it's a storm in a teacup. Nothing's going to happen.” I think people by that stage were thinking, this is actually quite serious. But nobody knew quite how big it was going to be’ (Cutts transcript). Similarly, Piers Ricketts, the chief executive of the Eastern Academic Health Science remembers being in a bar in London on the 4th of March where it was clear that people were starting to consider ‘whether they should cancel events and so on. Some of us actually said, “you know, this might be the last time that we meet”. It was a typical sort of City bar with loads and loads of people’ (Ricketts transcript).

The day after Ricketts met his friends in the bar, Professor Chris Whitty, the Chief Medical Officer for England, announced the first death of a patient with COVID-19 in the country (Gov UK March 2020). What was particularly disturbing was the fact that she had not been abroad so had clearly been infected in the UK. By now, there were 116 known COVID-19 cases in the UK and the UK government was warning it was ‘now highly likely that the virus would spread in “a significant way”’ (Marsh).

Figure 2.3: Photograph a person wearing mask and gloves while shopping on 15 March 2020 in North Finchley London. Credit: Philafrenzy, Wikimedia.

These figures were being closely watched by the Government’s Scientific Advisory Group for Emergencies (SAGE). An ad-hoc group of scientists and experts drawn from universities and industry, SAGE began meeting regularly from 22 January 2020 to discuss COVID-19. The group aimed to collect and analyse scientific evidence to help inform the government. As part of this, a number of them were reviewing and modelling various measures that could help slow down the spread of the virus. They were particularly aware of the dire situation unfolding in Italy, where the healthcare system was collapsing under the strain and hospitals were taking on the semblance of battlefield medicine with choices having to be made as to who to save. Doctors were having to decide who to put on the last ventilators (Farrar transcript).

Figure 2.4: Tweet put out by Sir Patrick Vallance, Chief Scientific Advisor to UK Government, 20 March 2020.

Many SAGE members feared staff in the National Health Service (NHS) would soon face the same dilemma in the UK four to five weeks down the line if no action was taken. Among the strategies considered was mitigation to slow down transmission of the virus so that health services did not get overwhelmed. This could be done through measures like general social distancing, school closures, case isolation, household isolation and ring-fencing the vulnerable (Parliament UK). Another option was to go for suppression by imposing a lockdown. Few wanted to go down the route of national lockdown like China which many viewed as too draconian. However, by early March 2020 the data was increasingly suggesting the UK had little option but to do so (Farrar). The turning point came on 16 March 2020, when an academic team, led by Professor Neil Ferguson, an epidemiologist and mathematical biologist at Imperial College, warned that even if multiple mitigation measures were not put in place the UK would experience far more hospitalisations than the NHS could cope with and approximately 510,000 deaths (Ferguson; Parliament UK).

Figure 2.5: COVID-19 UK dashboard: total UK cases as at 9:00am on 10 March 2020. UK Government Public Health Report: HPR volume 14 issue 5: news (10 and 11 March).

The Imperial group report was issued five days after Dr. Tedros Adhanom Ghebreyesus, WHO, director-general of the World Health Organisation, declared COVID-19 to be a pandemic. By this time, more 118,000 COVID-19 cases had been recorded in 114 countries and 4,291 people had died (WHO). Soon after this, a number of European countries went into national lockdown. This included Italy on 9th March, Spain on 14th March, the Netherlands on the 15th and France on the 16th of March (Parliament UK). For many in the UK, it seemed only a matter of days before the UK government would do the same, which it announced on 23 March. It was against this background of uncertainty and foreboding that COG-UK was beginning to take shape.