COVID-19 — Oxford researchers unlocking the new normal

A quiet Oxford in lockdown

As the days lengthen over the empty streets of Oxford, the distinctive golden oolitic limestone stands brightly in the spring sunshine. The cobbled streets, normally shadowed by crowds of tourists, students and locals, lie as exposed and bare as the rest of the city. Oxford feels frozen in time — turned to stone by the continuing lockdown in response to the COVID-19 pandemic.

The virus responsible — severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) — is a novel coronavirus that has reached across the world and forced unprecedented alterations to our lives and freedoms. Due to the observed genetic similarities, SARS-CoV-2 appears to likely originate from bat coronaviruses. Coronaviruses cause diseases in mammals and birds, and respiratory tract infections in humans. In human populations, COVID-19 spreads in a similar way to cold and flu bugs, carried within droplets created by coughs or sneezes that may then be inhaled or infect others through touching contaminated surfaces.

News headlines were increasingly overtaken by the Coronavirus. First reports from Wuhan Province in China felt deceptively detached from everyday life, hazed by the illusion of immunity by distance, and a desire to continue socialising in College Common Rooms, city streets and parks in spring bloom, or the weekly pub quiz. Soon though, virus hotspots grew in Europe, America and across the world, and life in this University town felt increasingly in flux. College social hubs shut down as pockets of illness hit students, staff and visitors, and the question of a catch-up in one of the local watering holes felt increasingly disquieting. Tourists slowly faded and crowds thinned, and the virus no longer felt confined to news headlines, as suddenly everyone had a friend, colleague or family member reportedly infected.

By late April, the virus had spread to 210 countries and territories, with over 3 million confirmed cases and over 200 thousand deaths. The unfortunate combination of such variable response by patients to the virus has added to the challenge of containment. While some patients will require hospitalisation, and for some of those intensive care and ventilation, up to ~18% may be asymptomatic, while a large majority recover after suffering mild symptoms manageable at home. This heightens the risk of transmission by those who are unaware of their infection, as well as during latency period before symptoms appear at all but the virus may still be infectious.

Locked down Oxford with its bikes, but not its people

The mass spread of COVID-19 and the pressure induced on healthcare infrastructure led the UK to implement a lockdown on 23 March 2020, closing all but essential workplaces, businesses, public services and freedoms. As well as the loss of the familiar structure to most of our daily lives through working remotely, home-schooling children, and virtual socialising only, at-risk members of society were requested to remain at home for 12 weeks with even less freedoms, relying on family to supply food and other essentials. Such measures appear to be slowing the virus’ spread, but with an inevitable substantial cost to our lives in other ways. The first 1.5 months of lockdown is estimated to have cost the UK economy 3.4% of its GDP, while the impacts of job losses, financial strain, bereavement, confinement and fear are inflicting a considerable strain on mental health, with effects likely to be deep and extend far beyond lockdown.

With a vaccine possibly months or years away, there is for now no shot-in-the-arm that will conjure up our old lives, and lockdown measures will eventually need to be lifted within a ‘new normal’ — a pithy phrase favoured by the government and journalists, but one that represents a whole new way of life, and a fragile one at that. It must be done without returning to the risk of overwhelming the health service and undoing the hard-won progress the lockdown has achieved. If all restrictions were lifted universally, this could trigger a rapid resurgence of infections and deaths.

As a hub of research institutes, well-equipped laboratories and bright minds, Oxford has been quick to respond to the crisis and lead in Coronavirus research, with teams pushing forward vaccine development, treatment testing, transmission and population health studies, government policy analysis and advice, communications and much more. One team on this frontline is the Oxford University Mathematical Ecology Research Group (MERG), led by Michael Bonsall, Professor of Mathematical Biology and Tutorial Fellow at St Peter’s College, a constituent college of the University. The team undertakes cross-disciplinary research using mathematical approaches to explore novel problems broadly concerning population biology through mathematical modelling combined with experimental or observational data.

The MERG team, in collaboration with Chris Huntingford from the UK Centre for Ecology & Hydrology, utilise an adapted Susceptible-Exposure-Infection-Recovery (SEIR) model framework — a compartmental model used in epidemiology that simplifies the mathematical modelling of infectious diseases. The population is divided into four compartments — Susceptible, Exposed, Infectious, or Recovered — individuals may move between compartments, and each disease has a unique combination of infection, latency and recovery rates.

Two potential lockdown release strategies were explored, focusing on the UK population as a test case. They found that ending quarantine for the entire population simultaneously is a high-risk strategy, and that a gradual re-integration approach would be more reliable. The number of us that may be freed from lockdown would also depend on the amount of new COVID-19 cases that continue to arise. An optimal control framework was applied to help tease out the highest proportion of us that may resume daily life and work, while safeguarding hospitals from another surge in cases.

Study lead author Thomas Rawson

Thomas Rawson, systems biology PhD student within the MERG group and lead author of the study, tells me that according to their work, the optimal strategy would involve releasing as many as half of the population 2 to 4 weeks after the initial infection peak.Thomas explains:

“Relaxing lockdown measures for too many people too soon risks a very high second peak in infection numbers, potentially overwhelming the health service.”

We would then have to wait another 3 to 4 months to await that second peak before risking releasing everyone else, meaning a new normal may be in flux for some time to come. The team also modelled an ‘’on-off’’ strategy, of releasing everyone, but returning to full lockdown if infections rose too high.
This though led to higher risk and more resurgence of the virus, and so Thomas cautions against lockdown-release strategies based on an on-off mechanism:

“Any exit strategy is likely to cause an increase in infections. However, we found that releasing everyone simultaneously could result in an acceleration in infections that rapidly overtakes the capacity of hospitals, and it would only be a few weeks until full lockdown measures would have to be reinstated.”

All models must rely on real-world information parameters, and for COVID-19 the two key factors are the transmission rate and recovery rate, as these specifically explain the length of time that an individual can remain infectious. The uncertainties around these as the COVID-19 knowledge still develops means accurate identifying and monitoring these could be key for deciding how we establish the next steps, highlights Thomas:

“Ongoing monitoring and an increase in testing capacity will be vital when easing lockdown measures to understand how infections are spreading compared to model predictions. Our models address the need to ensure that any increase in infections happens slowly enough that we are able to spot if things are worsening before it’s too late.”

Though no doubt many fear the prospect of many more months of lockdown, the sense of a plan and of a way out may salve some of the pains of uncertainty and unknowns that have characterised the lockdown. The dichotomy of the relentless presence of the COVID-19 in our lives, and yet the everchanging standing of where we are in the journey through the crisis, has contributed to the feelings of unsteady ground and uncertainty of where the exit strategy leads. Governments around the world have faced unique combinations of population densities and demographics healthcare infrastructure and public response, and each must decide on the next steps.

As 2020 marches on, a new normal will be found, and the work of Thomas and the MERG team, along with a vast network of researchers and support staff throughout Oxford, continues behind the quiet streets and closed doors of the city of dreaming spires, to help us find the way.

Read the Press Release from Oxford University regarding the study preprint here:
http://www.ox.ac.uk/news/2020-05-06-how-and-when-end-covid-19-lockdown-optimisation-approach

Read the preprint of: ‘How and when to end the COVID-19 lockdown: an optimisation approach’ here: https://www.medrxiv.org/content/10.1101/2020.04.29.20084517v1

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