Coronavirus – exit strategies

When will the pandemic be over?

The threat of COVID-19 will persist until there is sufficient immunity to fight the virus in the population, when the disease external page cannot spread because too few susceptible individuals remain, and that external page ‘herd immunity’ will either result when sufficient people have recovered from being infected with the virus or, more likely, an external page effective vaccine comes along (more on this later).

When’s that, exactly?

We’re less likely to see a quick victory and more likely a protracted guerrilla war against the virus, with waves of outbreaks and restrictions.

We could be talking about many months, even years, though this may change because scientific understanding is constantly evolving, for instance about the numbers of people who have been infected with COVID-19 without showing any symptoms, along with our means to curb outbreaks with testing/isolation.

Social distancing may need to be maintained intermittently into 2022, according to one computer model published last week by a team including external page Stephen Kissler, an infectious-disease modeler at Harvard.

A saw-toothed profile of outbreaks and lockdowns can be seen in a external page computer model (see figure 5) presented to Government in late February /early March by John Edmunds, Nicholas Davies and colleagues at the London School of Hygiene and Tropical Medicine (LSHTM).

It can also be seen in a mid-March external page computer model (see figure 4), by Neil Ferguson, Christl Donnelly, Steven Riley, Azra Ghani and colleagues at Imperial College London, consisting of the WHO Collaborating Centre for Infectious Disease Modelling, MRC Centre for Global Infectious Disease Analysis and Abdul Latif Jameel Institute for Disease and Emergency Analytics.

Who is going to win the war on COVID-19?

This will ultimately depend on an army of scientists, researchers, clinicians, mathematicians, engineers, technologists and external page technicians, who are engaged in a global effort of a scale and focus not seen since the external page Apollo program of moon landings.

Will COVID-19 abate this summer, like a seasonal infection?

Probably not. There has been debate about the extent to which external page COVID-19 is seasonal but the LSHTM team believes this will external page not be a significant factor, given the global spread of the virus.

Was a lockdown really necessary?

Yes. The LSHTM team briefed the UK Government in early March on how only a lockdown could protect hospital intensive care units from being external page overwhelmed.

In late February, the LSHTM started to model a range of measures to control the pandemic. On 10 March the team went on to consider the impact of a lockdown, at the time thought an unrealistic and draconian option.

Periodic lockdowns of a few weeks at a time could keep the pandemic at bay, so that the NHS could cope.

Their work was external page confirmed by Mark Woolhouse and colleagues at the University of Edinburgh, then by the Imperial team, which looked at the efficacy of various measures across Europe and found lockdown is by far the external page most efficient.

(Annotation: The effects of the measures in Switzerland are also being investigated in the study of the Imperial College London and results are external page graphically displayed.)

By 11 March, the day that external page Italy ordered a lockdown, these UK external page epidemiologists were agreed that a lockdown was the only option to ensure the NHS could cope. Lockdown allows hospitals time to manage their critical care capacity.

external page Spain ordered a lockdown on 14 March, external page France on 17 March, external page Belgium on the 18 March, external page Greece on the 23 March, along with the external page Netherlands, and the external page UK locked down on the 24 March.

(Annotation: external page Switzerland ordered a lockdown on 20 March. This corresponds to the date when the Swiss government external page banned gatherings of more than five people.)

The Imperial team has estimated that external page 59,000 lives were saved by keeping lockdown to the end of March in 11 countries.

Why not just carry on with the lockdown?

The economic cost of this blunt instrument of pandemic control is colossal.

The external page Office for Budget Responsibility has warned the pandemic could see the economy shrink by a record 35% by June, the largest drop in living memory.

The International Monetary Fund has described the global decline caused by the ‘great lockdown’ as the external page worst since the Great Depression of the 1930s.

(Annotation: The Swiss Economic Institute (KOF) at ETH Zurich calculated the potential effects of the COVID-19 pandemic on the Swiss economy back in March. At the beginning of April more specific scenarios were developed to estimate the economic impact from March to June 2020.)

When can we consider lifting the lockdown?

The Imperial model shows that we are external page around the peak of the UK epidemic and can expect cases to start to fall, so now is the time to think about relaxing the lockdown.

COVID-19 typically takes 20-25 days from infection to the death of a patient, in the most severe cases, though this figure can range from external page 14 days to 56 days. Given the UK lockdown was on 24 March, the impact of lockdown on death rates has only become clearer in the past few days.

The World Health Organisation’s Director-Genera, Dr Tedros Adhanom Ghebreyesus, has listed external page six criteria for countries to consider before lifting restrictions:

• COVID-19 transmission is controlled
• Health system capacities are in place to detect, test, isolate and treat every case and trace every contact
• Outbreak risks are minimized in special settings like health facilities and nursing homes; preventive measures are in place in workplaces, schools and other places where it’s essential for people to go
• Importation risks can be managed
• Communities are fully educated, engaged and empowered to adjust to the “new norm” of living with COVID-19

If we lift restrictions, what then?

As we have external page seen in Singapore, for example, we can expect cases to rise once again but, hopefully, not too quickly.

By external page one scenario from Kissler’s team at the Harvard T.H. Chan School of Public Health, Boston, resurgence in SARS-CoV-2 could occur as far in the future as 2025:

‘The total incidence of COVID-19 illness over the next five years will depend critically upon whether or not it enters into regular circulation after the initial pandemic wave, which in turn depends primarily upon the duration of immunity that SARS-CoV-2 infection imparts.’

Will testing help?

It’s critical. As the World Health Organisation criteria suggest, a massive and accurate programme of testing could help relax sweeping restrictions by enabling the authorities to focus on finding anyone with COVID-19, isolating people shown to be infected, tracing their contacts during the time the virus incubates, and either quarantining those contacts or testing them too.

South Korea showed how it is possible to track an infected person’s contacts rapidly by comparing their mobile phone activity with that of others in the same area.

How much do we know about population/herd immunity?

We don’t know what proportion of the UK population has already been infected and how long they will remain immune.

The computer modellers all agree that the total incidence of the virus for the next few years will depend crucially on the rate at which virus immunity wanes – of which scientists know little until they carry out more screening of the population.

By detecting such antibodies through what are known as external page serological tests (external page current testing mostly focuses on searching for the coronavirus’s genetic material rather than the antibody response) we could work out who has already been infected and, after testing for some time, how long that protection lasts.

That would be a huge help to scientists trying to understand the pandemic, since there are divergent estimates of how many people are already immune, which external page range from half, which seems unlikely, to the external page smaller percentages observed in hard-hit areas such as northern Italy, as Neil Ferguson of Imperial told the external page Science and Technology Select Committee.

The target for herd immunity is probably closer to 60% than 80% (if the coronavirus spreads more easily than the experts think, more people will need to get it to achieve herd immunity), according to John Edmunds of LSHTM.

However, it would take a lot of cases – and a lot of deaths – to achieve “herd immunity”.

The external page Health Select Committee was told by Anthony Costello, Professor of Global Health and Sustainable Development, UCL Institute for Global Health, that this current wave of infections could lead to around 40,000 deaths in the UK , exposing 10 – 15% of the population to the virus, and so it would take external page ‘five or six waves’ to reach herd immunity.

Perhaps the proportion of people with immunity could be raised relatively safely by relaxing restrictions on lower risk groups, such as the young.

Should we issue certificates to show who has immunity to the virus?

Immunity certificates have been discussed but we need to understand more about immunity to the virus, how long it lasts and the reliability of these tests, which has been external page questioned by Government advisor Sir John Bell of Oxford University. The challenges of developing and using antibody tests have been external page underestimated.

There are broader issues to consider, from attempts to falsify documents to issues about civil liberties. And, if uninfected people are desperate to get out of lockdown, immunity certification might motivate them to get infected as a pathway to freedom.

Presumably we can lift restrictions gradually?

That’s right. After all, external page in the UK restrictions were gradually introduced – external page perhaps too gradually – from asking people with symptoms to self-isolate on 12 March to avoiding pubs, theatres and so on 16 March, school closures on 21 March and then a lockdown on 24 March.

(Annotation: In Switzerland, the restrictions were also gradually introduced: On 24 February people were asked to external page self-isolate when experiencing coughing and fever; on 28 February the government external page banned large-scale events with more than 1,000 people; on 2 March hygiene measures were external page intensified; a ban of public events with external page more than 100 people followed on 13 March as well as the external page closure of schools; on 16 March the government declared an external page ‘extraordinary situation’ and introduced more stringent measures by closing all shops, restaurants, bars and entertainment as well as leisure facilities until 19 April and by re-introducing checks at the border to neighbouring countries; a complete lockdown followed on 20 March when it was announced that external page gatherings of more than five people were banned.)

A key issue is how to relax these measures in a way that allows the pandemic to be kept at an “acceptable” background level.

There are lots of options. A team at the University of Cambridge has external page identified 275 non-pharmaceutical ways to reduce transmission of the coronavirus, from curfews and community shopping to staggered working hours, the use of bicycles to avoid public transport, opening windows on public transport, and encouraging one-way routes around buildings and other spaces.

What can we learn from other countries?

We can learn a lot, particularly from countries closer to the epicentre of the pandemic. Most governments around the world have temporarily closed educational institutions and UNESCO estimates that more than 1.5 billion learners – over 90% of the world student population – are confined to their homes.

On this external page UNESCO website you can see when schools have been closing locally, at a national level, and then reopening again during the pandemic. Germany, for example, will allow external page schools to open from 4 May.

(Annotation: In Switzerland, mandatory schools are scheduled to external page re-open on 11 May, while upper-secondary schools, vocational schools and higher education institutions are planned to follow on 8 June. More details on the gradual ease of measures against the COVID-19 virus in Switzerland can be found in the government’s external page media release from 16 April. )

Education is changing as a result, and not just moving online. In Wuhan in China, the epicentre of COVID-19, more than a million primary and secondary students have participated in “air classes” since February, for example.

The external page Royal Society has also created external page DELVE: Data Evaluation and Learning for Viral Epidemics, a group to study different approaches countries are taking to managing the pandemic. This effort will provide input through SAGE, the Government’s scientific advisory group for emergencies.

What can we learn from the 1918 flu pandemic?

Social distancing was external page shown to be effective in US cities, along with quarantine, during this devastating pandemic, says Laura Spinney, author of external page Pale Rider: The Spanish Flu of 1918 and How it Changed the World.

For example, when the influenza arrived in Iceland, word quickly spread and a combination of measures helped keep more than a third of the population flu-free.

However, the dangers of relaxing these measures too quickly also became apparent, said Spinney:

‘Australia put in place a very effective maritime quarantine that kept out the second wave. The problem was that it lifted it too soon and let in the third wave, in which 12,000 Australians died.’

(Annotation: How Switzerland dealt with the Spanish Flu in 1918 and 1919 can be found in external page this article by NZZ and external page this article by SWI.)

What other insights do we have into the extent of the pandemic?

There are indirect ways to chart the extent of the pandemic that don’t depend on testing.

external page A paper by one American team found flu-like symptoms not caused by influenza have surged and in places where there has been a rise in COVID-19 cases, suggesting larger numbers of people with mild-to-moderate symptoms.

More than two million people have downloaded an app – the external page COVID Symptom Tracker app – in what may be the UK’s biggest ever citizen science project and that has shown how the rate of new symptoms being reported nationally has slowed significantly as a result of the lockdown.

Such surveillance could help relax the need for active testing, for instance revealing hot spots at which to focus active testing.

(Annotation: To track the occurrence of COVID-19 cases and symptoms in Switzerland, a external page platform has been developed. On this platform, people are asked to report their health status whether they are sick or healthy in order to identify cases (and potential outbreak hotspots) as early as possible. Other efforts to deal with the spreading of the virus are being developed in Switzerland as well. A team of researchers has managed to develop external page a sensor to monitor the concentration of the COVID-19 virus in air. However, the sensor is not yet ready to be set up in e.g. public places.)

Will drugs help to bring the crisis to an end?

They will certainly help. New treatments could alleviate the need for stringent social distancing, though most drugs work for no more than around 50% of the population, roughly speaking (most common medications have external page small-to-medium effects).

Even so, if a drug can cut the risk of hospitalisation, or ventilation, that would save many lives.

What about face masks?

The science says yes, external page according to Prof Trisha Greenhalgh of the University of Oxford.

This is more a matter of protecting others than yourself, though the external page evidence from “gold standard” randomized controlled trials is not particularly compelling.

Patients with COVID-19 may shed virus two or three days before first symptoms, external page according to Eric Lau of Hong Kong University and colleagues, while the team at the Centre for the Mathematical Modelling of Infectious Diseases (external page CMMID) at the LSHTM have external page estimated from data in Shenzen, China, that 23% of transmissions came from people who had not developed symptoms.

Bottom line: as Prof Greenhalgh says, face masks may well help curb the pandemic, though homemade might be preferable – external page ideally more sophisticated than a simple scarf or bandana – so as not to put pressure on the supplies of medical grade masks needed by health-care workers. They have to be external page used properly too.

(Annotation: At the moment, external page the Swiss government recommends that protective materials such as face masks, glasses and gloves are used carefully as not to create a shortage. It is most important that enough protective materials are available for medical personnel treating infected patients as well as for people with a high risk of becoming severely ill.)

How quickly can we get a vaccine?

The most reliable endgame – as pointed out in an earlier external page blog post in this series – is to suppress the pandemic with testing/isolation, social distancing and lockdowns until an effective vaccine can be distributed.

Around 140 COVID-19 vaccines are in development worldwide, according to Sarah Gilbert of the University of Oxford on BBC Breakfast this morning (tune in external page here at 1:14:38), whose team is starting a vaccine trial later this week.

The global effort has also seen GlaxoSmithKline and Sanofi external page join forces, which together have the largest vaccine manufacturing capability in the world.

However, these efforts are flying blind in the sense that they don’t know enough about the optimum immune response to protect against the COVID-19 virus, SARS-CoV-2.

They need a dose of luck: I talked to a researcher who injected himself with an experimental Aids vaccine more than three decades ago, external page in 1987, and we still external page don’t have an effective vaccine to combat the human immunodeficiency virus (fortunately AIDS is now a external page manageable chronic disease, thanks to drugs).

Even so, there is optimism that a COVID-19 vaccine could take as little as a year to 18 months to develop.

At the end of this week, a team at the University of Oxford will start testing a vaccine – external page ChAdOx1 – based on a safe version of an adenovirus, which it is hoped will generate longer-lasting immunity than coronavirus.

Compressing five years work into four months, the Oxford team, led by Sarah Gilbert, Andrew Pollard, Teresa Lambe, Sandy Douglas and Adrian Hill, has modified the adenovirus to make the “spike” protein that this coronavirus uses to invade human cells.

Gilbert expects 500 volunteers to be vaccinated by mid-May and, if all goes to plan, her external page COVID-19 vaccine might be ready by the autumn. (NB, even if it works, there are still major questions about scaling up the manufacture of the vaccine and the UK does not have the capacity to do this).

She is confident because her team has been working on a vaccine against another coronavirus, external page Middle East Respiratory Syndrome (MERS).

‘Preclinical data on several Middle East Respiratory Syndrome coronavirus vaccines shows them working in animal models, including the fact that antibodies induced after vaccination external page can neutralise a wide range of strains of MERS coronavirus isolated in different countries at different times. So the prospects are very good for being able to produce a vaccine against SARS-CoV-2.’

Another reason Gilbert is confident is because there are licensed veterinary vaccines against coronaviruses.

Mike Francis of the external page UK Vaccine Network, who has developed successful commercial vaccines for bovine coronavirus, canine enteric coronavirus and avian infectious bronchitis virus, said the bovine vaccine – Rotavec Corona – gives external page important insights into the immune protection, which is passed on to calves – ‘in this particular instance the external page mode of protection is very clear.’

‘I am cautiously optimistic,’ said Francis, referring to Oxford’s ChAdOx1 vaccine against COVID-19.

‘I do have one note of caution regarding safety,’ he said, referring to attempts to develop a vaccine against the cat coronavirus, Feline Infectious Peritonitis, which have run into problems with Antibody-Dependant Enhancement, when the vaccine makes it easier for the virus to infect animals that have received the coronavirus vaccine.

He added that AIDS has proved a challenging target for vaccine manufacture due to specific features of the human immunodeficiency virus, from the way it integrates its genetic code into the human host, the variability of the virus coat proteins and the way it targets human immune system cells.

Sir Patrick Vallance, Government chief scientific adviser, said:

‘The UK has a proud history in vaccinology. It was an Englishman, external page Edward Jenner, who pioneered the field over 200 years ago. Two centuries on, the scientific community will work tirelessly to find a medicine or vaccine against Covid-19, and we need to back them every step of the way.’

You can read the full comment piece external page here.

(Annotation: In Switzerland, various medical research institutes are also developing and testing coronavirus-vaccines (for more information on these efforts see external page this article by SRF). ETH Zurich is also involved in the search for active substances and vaccines against the COVID-19 virus.)

Does the official death toll accurately capture COVID-19-related deaths?

The toll is likely to be an underestimate, according to David Spiegelhalter, Chair, Winton Centre for Risk and Evidence Communication at the University of Cambridge.

Leaving aside delays in in reporting, or those people who died before they could be tested, the external page official total based on NHS hospital deaths is smaller than external page the figure shown by the Office of National Statistics: deaths involving COVID-19, with a date of death up to 3 April, are 15% higher than the NHS numbers as they include all mentions of COVID-19 on death certificates, including suspected COVID-19, as well as deaths in the community and care homes.

However, ONS statistics reveal a massive rise in non COVID deaths on April 3 and Sir David wonders whether doctors are being cautious about putting COVID-19 on the death certificate without testing – we may still have an incomplete picture of the death toll.

Government announcements have focused on deaths in hospital not least because records of confirmed cases depend on the quality of the testing regime – which has been patchy and taken longer to introduce than originally thought. Moreover, some COVID carriers show no symptoms and thus would not have been tested.

Other complex issues confound discussion of death rates: how many of those who died of COVID-19 would likely have died anyway of other underlying health conditions, and what is the “collateral damage” caused by the pandemic, for example if seriously-ill people – such as those who have suffered strokes and heart attacks – are less inclined to go to hospital, and the toll on patients with other serious illnesses as tests, treatments and operations are delayed or cancelled.

What is the overall state of the pandemic?

You can get the latest news on how far this pandemic has spread worldwide from the external page Johns Hopkins Coronavirus Resource Center, compare the state of the pandemic in Europe using external page these data and forecasts from Imperial College London, external page see the UK hotspots identified by the symptom tracker app and check the number of UK COVID-19 cases by consulting external page Public Health England data.

There is more information external page in my earlier blog posts, from the external page UKRI, on this external page COVID-19 portal and external page Our World in Data.

(Annotation: The current number COVID-19 cases in Switzerland can be found on the external page Federal Office of Public Health’s website.)