This isn’t how any of us thought 2020 would turn out. Last December, as people gathered in swathes to celebrate the festive season, it seemed inconceivable that an unknown virus was about to sweep across the world, changing life as we know it.
Six months ago, we plotted the defining moments of the COVID-19 pandemic as Britain began to emerge from its first national lockdown. Now, as the year comes to a close, we explore what has changed, what the world has learned, and how Imperial research has driven forward our understanding of the disease that has come to define 2020.
Early infection fatality ratio predictions were pretty accurate
In March, just as Britain entered its first lockdown, Imperial’s COVID-19 Response Team estimated the ‘infection fatality ratio’ for COVID-19. These early predictions suggested an overall infection fatality ratio of 0.9% for the UK.
The infection fatality ratio (IFR) is a key statistic for estimating the burden of COVID-19 and has been continuously debated throughout the current pandemic. It reflects the proportion of deaths among people infected with the virus, commonly referred to as ‘the risk of death’.
More than seven months on, these early predictions were vindicated by the Real Time Assessment of Community Transmission (REACT) study, as well as a new report by Imperial’s COVID-19 Response Team, which confirmed an infection fatality ratio of around 1% for high income countries based on the latest antibody surveys.
The report also found that the risk of death from COVID-19 doubles for approximately every eight years of ageing and is substantially lower in low-income countries with younger populations.
Dr Nicholas Brazeau, co-author of the study, said: “Estimates of the IFR are difficult given the many biases of data collected during an outbreak. Using a statistical model, we partly reconcile these biases and help to explain country-specific differences. Overall, we suggest that age differences will have the largest effects, as regions that were hit hardest by the pandemic did not necessarily have higher IFRs.”
Danish mink could threaten vaccine efforts
In early November, Denmark – the world’s largest exporter of mink fur – announced that it would cull as many as 17 million mink over fears that a mutated form of coronavirus spreading between the farmed animals and humans could hamper vaccine efforts.
When viruses move between humans and animals, genetic modifications can occur. This is a concern because significant mutations to the virus might mean that vaccines and treatments under development do not work as well. In Denmark, some mutated strains involved the spike protein of the virus which is targeted by multiple vaccines being developed – including Imperial’s and the Pfizer vaccine recently approved for use in the UK.
Speaking on The Andrew Marr show, Professor Wendy Barclay, a virologist at Imperial who sits on the Government’s SAGE committee, explained that the close proximity of farmed mink creates an environment where viruses can mutate rapidly as they spread between the animals. Other animals, like cats and dogs, have been reported to have caught COVID-19 from humans, but they are not likely to be kept in the same crowded conditions, so this is much less of a concern.
Virus mutations cause challenges for immunising other illnesses too, such as influenza. A vaccine platform which is flexible and fast responding would allow us to develop future generations of vaccines that could be tweaked if needed to protect against mutated strains, Professor Barclay said.
Human challenge trials could unlock new insights into the virus
In October, Imperial announced that it would be the first in the world to explore a human challenge study with the virus that causes COVID-19.
A human challenge study involves deliberately exposing healthy volunteers to a particular pathogen to learn more about the disease it causes and accelerate the development of new drugs and vaccines. Their use has been pivotal in developing vaccines and therapies for illnesses such as typhoid, cholera and malaria, and has helped to drive forward our understanding of how the immune system responds to viruses such as influenza.
This kind of study could be especially useful with coronavirus, because the prevalence of the virus rises and falls in populations. This can make it difficult for traditional vaccine trials to assess if vaccines work, because volunteers receiving the vaccine may not be naturally exposed to the virus.
To begin with, the trial will aim to discover the smallest amount of virus it takes to cause a person to develop COVID-19. After this, researchers aim to use this human challenge model to study how vaccines work in the body to stop or prevent COVID-19, to look at potential treatments and study the immune response.
Dr Chris Chiu from the Department of Infectious Disease at Imperial and lead researcher on the human challenge study said: “Human challenge studies can increase our understanding of COVID-19 in unique ways and accelerate development of the many potential new COVID-19 treatments and vaccines.
“Our number one priority is the safety of the volunteers. My team has been safely running human challenge studies with other respiratory viruses for over 10 years. No study is completely risk free, but the Human Challenge Programme partners will be working hard to ensure we make the risks as low as we possibly can."
The Human Challenge Programme is a partnership between Imperial College London, the Department for Business, Energy and Industrial Strategy (BEIS), hVIVO, a leading clinical company with expertise in viral human challenge models, and the Royal Free London NHS Foundation Trust.
The study is expected to begin early next year, with further details of volunteer recruitment and the study design to be published in the coming months.
COVID-19 amplifies existing inequalities
As the pandemic in the UK worsened, it became apparent that COVID-19 was having a disproportionate impact on ethnic minority groups.
A report from Imperial’s COVID-19 response team in April 2020 found that Black patients admitted to hospital with COVID-19 tended to be younger, have fewer pre-existing health conditions, and have worse health outcomes. A Public Health England inquiry later confirmed that people from Black, Asian and other ethnic minority (BAME) groups are dying disproportionately from COVID-19. In October, the Government’s COVID-19 risk algorithm identified a BAME background as one of the top risk factors for serious illness or death.
Sonia Saxena, Professor of Primary Care at Imperial and an expert on health disparities in minority ethnic groups, said the situation is a result of “intersecting pandemics, COVID-19 and endemic racism.”
Professor Azeem Majeed, head of the Department of Primary Care & Public Health at Imperial, added: “COVID-19 has shone a spotlight on inequalities that have existed for years and made them very stark. We need to learn the lessons of COVID-19, but we can’t forget other inequalities among ethnic groups that already existed, such as in education, income and housing. All of government needs to address the underlying causes of those inequalities.”
This is now an urgent area of research and policy response in the UK. Earlier this year, Imperial experts offered a number of policy suggestions that could help tackle the problem.
We can’t rely on herd immunity
In October, Imperial findings dealt a blow to hopes that herd immunity might offer protection from COVID-19.
Findings from the Real Time Assessment of Community Transmission (REACT) study showed that antibody response to the virus that causes COVID-19 wanes over time.
Led by Imperial researchers, the analysis of finger-prick tests carried out on more than 365,000 people in England between 20 June and 28 September found that the number of people testing positive for COVID-19 antibodies dropped by 26.5% across the study period, from almost 6% to 4.4%.
The decline was largest in people aged 75 and above compared to younger people, and also in people with suspected rather than confirmed infection, indicating that the antibody response varies by age and with the severity of illness. It was observed in all areas of the country and age groups, but not in health workers, which could indicate repeated or higher initial exposure to the virus, the authors suggest.
Professor Helen Ward, one of the lead authors of the report, said: “This very large study has shown that the proportion of people with detectable antibodies is falling over time. We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
Hopes were further dashed in November, when a surge of new infections and hospital admissions in Sweden indicated that the country’s light-touch, anti-lockdown approach had failed to prevent a second wave through immunity in the population.
To vaccinate the world, we need global collaboration
When Imperial bioengineer Dr Anna Blakney’s colleague Professor Robin Shattock first approached her at the start of 2020 to propose that they start working on a vaccine for the novel coronavirus, she thought their time would better spent focusing on other projects. Fast forward almost one year and Anna is playing a key role in the Imperial vaccine team whose work is being followed by people around the world.
Anna’s work focuses on the pre-clinical development of the vaccine, including animal testing done before the vaccine candidate is moved into the clinic. The aim of this stage is to make sure that the vaccine has an effect, works well, and is safe in animals.
This is a well-defined process, but the speed at which vaccine candidates are being developed has led to public concern that vaccines for COVID-19 are being rushed. This fear, Anna says, is unfounded.
Researchers, clinicians and clinical trial administrators worldwide, including Anna and the rest of Imperial’s vaccine team, all stopped what they were doing as news of a new coronavirus emerged, and started to focus entirely on COVID-19. This unprecedented global effort and focus, combined with new technology, meant that vaccines could be made at a greater speed than ever before. “Usually, people aren’t just working on one project. One thing we learned is that when everybody works together so cohesively and collaboratively, we can move at amazing speed. Never before have we had the motivation or financial resources to do anything so quickly on such a large scale,” Anna said.
Unfortunately, misinformation around vaccines is pervasive and Anna recognises the importance of communicating to the public. That’s why she’s teamed up with Team Halo, a United Nations initiative that goes behind the scenes with the scientists trying to develop a COVID-19 vaccine.
She said: “It’s been a really eye-opening experience because it showed me what people are concerned about. Especially for these new types of vaccines. Most of the general public don’t know what an RNA vaccine is. Some scientists don’t even know what an RNA vaccine is! Being able to directly communicate to people, answer their questions, explain things, and have that come from a scientist, is a really important thing in society.”
“I don’t think anything really compares to it. We’re trying to vaccinate the whole world right now and we’ve never had to do that before.”
It's a race against the virus, not each other
On 8 December 2020 Margaret Keenan became the first person in the world to be given the Pfizer COVID-19 vaccine.
On 8 December 2020 Margaret Keenan became the first person in the world to be given the Pfizer COVID-19 vaccine.
As scientific teams around the world launched their efforts to develop a vaccine for COVID-19, and the first vaccine starts to be rolled out, they were often portrayed as opponents. But Imperial scientists say that the race is against the virus, not each other.
On 8 December, the first person received Pfizer/BioNTech vaccine in the UK. On the news that it had been approved for widespread use by the medicines regulator, the MHRA, Professor Danny Altmann from Imperial’s Department of Immunology and Inflammation told the BBC: “Immunologists, vaccinologists and virologists have been working on these kinds of questions, and these kinds of vaccine platforms, for many years. Getting out of bed every morning to do the job on the basis it would matter one day and now it really does matter.
“We shouldn't get too bogged down in the first vaccine, or the race, who’s won the race or who has approved it fastest or anything like that. We all know the pandemic has been devastating. The fight to win back all that lost ground and get on top of this will be a long and hard one and we’re going to need many months of many vaccine doses of many types in many countries to get there.”
"It's amazing that vaccines are coming through in a way we didn't anticipate and at a level of efficacy way higher than anybody had expected, so it's an amazing success story."
It is collaboration, not competition, that will enable vaccine efforts to succeed. That Imperial is a key trial site for the other UK-led effort to develop a vaccine, from Oxford-AstraZeneca, as well as leading its own COVID-19 vaccine trial, attests to this.
Genetics could predict if you’re likely to get severe COVID-19
For Dr Vanessa Sancho-Shimizu, there has never been a busier period of her career. While her research normally focuses on the genetics of life-threatening infections in children, it made sense to turn her focus to COVID-19 at the start of the year.
Early on, Vanessa and colleagues from the COVID Human Genetic Effort proposed that there may be a genetic predisposition for severe cases of COVID-19, where a patient is admitted to hospital, requires oxygen, spends time in intensive care or dies.
It was well established that proteins called type 1 interferons, which provide first-line defence against infection by heightening our cells' anti-viral defences, predispose to acute respiratory distress syndrome and severe flu. COVID-19 shares similar features to severe flu, so could it be that the same genes are involved?
Through collecting and analysing DNA, mutations in the type 1 interferon pathway in patients with severe COVID-19 were identified, with studies revealing that at least 3.5% of patients with life-threatening COVID-19 were missing a functioning gene that controls type I interferons.
More than 10% of those studied had auto-antibodies to type I interferons - misguided antibodies that attack the immune system itself, not the virus. As 94% of those with autoantibodies were men over 50, the findings could explain the age and gender bias among those with severe disease.
This research on a global scale allowed researchers like Vanessa to understand that type I interferons are important in preventing severe disease. Going forward, patients could be screened for autoantibodies or defects in their production of type I interferons, to predict if they may suffer severely, or administered type I interferons to prevent the disease becoming serious.
And how was it to be working on cutting-edge science during a pandemic? “It’s been an incredible experience scientifically to be in a research setting where we have learned so much in such a short time. It really is attributable to the scientific community coming together,” said Vanessa.
Coronavirus particles are infectious in the air
When COVID-19 was first emerging and little was known about its spread, public health officials advised people to wash their hands frequently, avoid touching their face and disinfect surfaces. This was based on studies of how other similar diseases spread, such as the common cold.
Experts initially thought that the virus was transmitted through large drops of mucus and saliva, emitted when people sneeze or cough, and that these droplets were heavy enough to drop out of the air quickly. These drops would fall onto surfaces; hence handwashing being identified as a key prevention measure.
We now know that the virus is emitted in a variety of droplet sizes, with some particles small enough to persist in the air, known as aerosols – especially in indoor, poorly ventilated spaces.
With this emerging evidence that coronavirus could be spread by tiny particles suspended in the air, in early July the World Health Organisation began to advise widespread use of face coverings.
Professor Wendy Barclay told My London: “The way the virus gets out of one person and into another is through droplets. We emit them all the time. If you think about just walking down the road on a cold day you can see this mist just walking along. That’s the respiratory droplets that you’re emitting all the time.
“It is a completely altruistic thing to wear a face mask. Your own droplets get caught in the face mask and you reduce how much you pass on to someone else.”
Tests can be taken out of laboratories and onto the frontline
A DnaNudge testing device
A DnaNudge testing device
Like many others at the onset of the pandemic, Professor Chris Toumazou repurposed his expertise and helped to take COVID-19 tests from the lab to the frontline.
Before the emergence of COVID-19, DnaNudge, an Imperial startup co-founded by Professor Toumazou and headquartered in White City, focused on a consumer service to encourage healthy eating. Their in-store DNA testing service analyses and maps a user’s genetic profile to key nutrition-related health traits.
DnaNudge adapted this into a rapid, lab-free COVID-19 test which offers gold-standard accuracy and sample-to-result in around an hour, compared to the current lab-based PCR testing, which can take 1-2 days to return results. It was approved for clinical use by the Medicines and Healthcare Products Regulatory Agency (MHRA) at the end of April, following successful patient trials.
The Lab-in-Cartridge rapid testing device can be performed at a patient’s bedside and was shown to have over 94% sensitivity and 100% specificity. The test is currently being used successfully across eight London hospitals and is due to be rolled out a national level.
Professor Graham Cooke, lead author of a study of the test’s sensitivity and specificity said: “These results suggest the test, which can be performed at a patient’s bedside without the need to handle any sample material, has comparable accuracy to standard laboratory testing. Many tests involve a trade-off between speed and accuracy, but this test manages to achieve both. Developing an effective bedside test in under three months has been an incredible collaboration between teams of engineers, clinicians and virologists.”
Quickly detecting the presence of the virus means that positive cases can be identified and contained quickly and safely.
Cheap existing drugs can help fight COVID-19
In the short time we’ve known about COVID-19, medical researchers have identified treatments that work to limit the disease or shorten its duration, many that were already on the market.
An inexpensive and commonly used steroid, dexamethasone, can help save the lives of seriously ill patients. The RECOVERY trial, led by Oxford University, showed that the widely available drug cut deaths by up to a third for patients on ventilators, and by a fifth for those on oxygen.
An anti-viral medicine used against Ebola, remdesivir, was one of the first treatments to emerge for COVID-19, with initial trial evidence suggesting it may shorten the time to recover from infection. In November, the World Health Organisation issued a recommendation against the use of remdesivir as there is currently no evidence it improves survival and other outcomes in hospitalised patients.
A study from Imperial researchers found that treating critically ill patients with the steroid hydrocortisone improves their chances of recovery. The study, led by Professor Anthony Gordon, found that patients in intensive care who were treated with a regular fixed dose of the steroid for seven days had a better chance of recovery, compared with those who were not treated with the steroid.
Professor Gordon said: “At the beginning of the year at times it felt almost hopeless, knowing that we had no specific treatments. It was a very worrying time. Yet less than six months later, we've found clear, reliable evidence in high quality clinical trials of how we can tackle this devastating disease.”
COVID-19: Lessons from the year that changed the world
Words: Joanna Wilson and Deborah Evanson
Photography: Thomas Angus / Imperial College London