Human challenge studies in the study of infectious diseases
What can deliberately infecting healthy people tell us about infectious diseases? How is this useful for developing treatments, and how do we manage the risks?
The UK Government announced its approach to exiting lockdown on 10 May in a statement by the Prime Minister and in a report published on 11 May. Current models suggest that 5.38% of the UK population has been infected with COVID-19. To lift restrictions the World Health Organisation has outlined key criteria that should guide decision making, such as ensuring that health systems can identify, isolate, test, trace contacts and quarantine COVID-19 cases. Several countries have eased measures with varying success including, Austria, France, Germany, Italy, Spain and China. Other countries such as Sweden and South Korea have taken alternative routes.
The UK Government announced its approach to exiting lockdown on 10 May in a statement by the Prime Minister and in a report published on 11 May. The exit strategy is based around a phased approach to returning to normal everyday activities across all aspects of life, over a period of several weeks leading up to the summer. This article compares the range of restrictions introduced by some national governments in response to the pandemic and compares the approaches in place for easing them. Some countries have suppressed the transmission of COVID-19 without imposing all types of restrictions on daily life.
The impact of lockdown policies and other sets of restrictions is demonstrated by the reduction in the spread of COVID-19 in the population. This can be described using a measure called the reproduction number (R). This is the average number of people infected by each person who has COVID-19 and so describes how an infection is transmitted within a population. If R is more than 1, an infection will move through a population. R cannot tell you how many cases there are; its value lies in indicating whether numbers of infections are increasing or decreasing. The aim of public health measures is to reduce R to below 1, as this will stop or slow the infection from spreading. While R is being used as a proxy to examine how well COVID-19 is controlled, other data are used to inform UK Government policy decisions, such as the capacity of critical care beds in hospitals, the number of confirmed infections and the death rate. The Office for National Statistics also publishes mortality data, with more detailed figures on sex, age and links to occupation.
At the beginning of the pandemic, the Scientific Advisory Group for Emergencies (SAGE) assessed that R in the UK was between 2.7 and 3.0; in other words, each person with the disease infected up to another 3 people on average. At the time of writing, R is estimated to be between 0.5 and 0.9 for the UK as whole (regional figures for R are in development). It is not possible to have a precise value for R at any given time, because a person can be infectious for approximately 10 days and there will always be a time lag in reporting, sometimes up to 2 weeks. UK-wide data on the number of confirmed cases and deaths are updated daily on the government COVID-19 data dashboard website.
Academics at the MRC Centre for Global Infectious Disease Analysis at Imperial College London have used modelling that has estimated that the percentage of the UK population that has been infected with COVID-19 over the course of the pandemic is 5.38%. Modelling data provided to SAGE indicates that relaxing all social distancing measures and fully opening schools will lead to a resurgence of the infection as R rises above 1, with a second wave that could be larger than the first, in a population where most people are not immune to the virus. Therefore, control measures will be lifted in phases. They could also be re-introduced, if R were to increase. Some countries are lifting measures at regional level, and could reimpose restrictions if necessary, for example in France. This relies on the ability to monitor the transmission of the virus at that geographical level.
The key to reintroducing elements of normal life – such as reopening workplaces and schools, and allowing people to use public transport or to gather in social venues – is to reconnect small, discrete networks of people without reconnecting the whole network that would allow the infection to spread. This is the key goal of lockdown exit strategies. It is likely that some measures that form part of national approaches to suppress viral transmission will need to be switched on and off or sustained over a long period of time (until a vaccine is available). In countries that are in later phases of the pandemic where restrictions have been relaxed, subsequent outbreaks of COVID-19 have been detected. This has required national governments to move quickly to identify, isolate and contain these clusters, to break the chain of transmission.
The aim of exit strategies is to allow life to return to normal as quickly as possible, whilst safeguarding against a resurgence in infections and minimising other indirect health impacts. The speed at which measures are lifted is a complex interplay between the adherence of the public with the measures; the national infrastructure to identify, isolate and treat those who are infected; and the strength of national surveillance mechanisms that detect changes in the transmission of the virus. There is a degree of risk associated with lifting each measure.
The World Health Organization has outlined the key criteria that should guide national decision- making on lifting restrictions:
Local epidemiological circumstances will inform policy-making between countries that are experiencing the pandemic differently or that are in different phases of it. As countries seek to lift the restrictions imposed on their citizens, shared principles have emerged, although countries have taken different approaches on how measures are applied:
The following section outlines the timelines and approaches taken by some countries and the impact of lifting some lockdown restrictions on the transmission of COVID-19 in the population where data are available. It is not possible to judge such impacts for about 14 days, so many countries impose measures for 3 weeks and then review the outcomes. Two countries that have suppressed COVID-19 transmission without enforcing a strict lockdown are also discussed – Sweden and South Korea.
Date lockdown started: 16 March
Date lockdown restrictions eased: 14 April
Estimate of total population infected: 0.76%
Modelling data estimates that the lockdown in Austria had an immediate impact on transmission, with R decreasing to below one straight away. See the Austrian government’s national COVID-19 data dashboard.
The Austrian Government announced a phased plan for easing restrictions on 6 April; the measures will be reviewed every 3 weeks.
Childcare and educational settings
A staged timeline for school openings is planned over several weeks. Pupil numbers in classes will be reduced by splitting them into groups with alternate teaching periods. Parents have the right to withdraw their children from school this year.
Workplaces
Most premises allowed to open from 1 May. Shorter working hours are in operation for 3 months provisionally, principally as an economic measure.
Shops and services
Small shops, garden centres and DIY stores re-opened from 15 April. Face coverings for staff and customers obligatory. Capacity is limited, one customer per 20 square metres. All other shop types and hairdressers were permitted to open from 1 May.
Social and cultural venues
Restaurants, bars and hotels will be one of the last sectors to re-open, from mid-May. Restrictions on opening hours are expected. Parks opened 14 April (social distancing of 1 metre applies). Museums and libraries re-open from 15 May.
Transport network and personal travel
Face coverings are obligatory and social distancing of 1 metre applies to those people outside one’s household. There are no limits on the use of the transport network.
Personal social activities
Events with more than 10 people are prohibited. Funeral gatherings of up to 30 people are permitted; social distancing applies.
Sport
No spectators permitted at sporting events until the end of June and all sports facilities are closed. Elite athletes and teams are permitted to train.
Mass gatherings
Theatres, opera houses and cinemas remain closed until the end of June. Other large public events are not yet permitted. Guidance for how these activities might be carried out is in development.
Religious worship
This will be permitted from 15 May. Mandatory face coverings and social distancing of 1 metre applies.
Date lockdown started: 17 March
Date lockdown restrictions eased: 11 May
Estimate of total population infected: 3.48%
Modelling data estimates that the lockdown in France had an immediate impact on transmission, with R decreasing to below one straight away.
The Government has announced that the first part of the exit strategy will last until 2 June. An evaluation of the situation will then inform subsequent actions, the next phase of which is intended to run from 2 June until summer (for which no specific date is cited).
Childcare and educational settings
Parents have the right to home educate their children, using a national distance learning programme.
Workplaces
From 11 May workplaces are authorised to re-open but social distancing rules will apply. Home working should be maintained wherever possible for at least 3 weeks from 11 May.
Shops and markets
These will re-open from 11 May (except those in shopping centres).
Social and cultural venues
Cafes, restaurants and bars will remain closed. A decision for proposed re-opening from 2 June will be taken at the end of May.
Transport network
Increased service levels across the public health network, with the public train network running at 70% of its normal services from 11 May. Passengers will be required to leave every other seat empty. Face coverings will be obligatory on buses, school buses, Paris Métro, taxis and other private hire vehicles.
Personal travel
Travel further than 100km from home address prohibited. Exceptions made for essential work or family reasons.
Personal social activities
Social gatherings, such as weddings and birthdays, are limited to 10 people.
Sport
Prohibited in public places. The 2019–2020 professional sport season remains suspended.
Mass gatherings
This includes concert venues and museums for example. Gatherings of more than 5,000 people are prohibited until September. Other cultural venues such as small museums can re-open from 11 May.
Religious worship
No services until 2 June.
Date lockdown started: 22 March
Date lockdown restrictions ease: 20 April
Estimate of total population infected: 0.89%
Modelling data estimates that the lockdown in Germany had an immediate impact on transmission, with R decreasing to below one within days. As of 14 May, Germany reports R at 0.88. With an R estimated at approximately 4 between February and early March, initial measures to advise social distancing (12 March), followed by school closures (14 March) had only a moderate impact on transmission.
The national data dashboard on COVID-19 in Germany is updated daily.
The Government announced their phased approach to lifting restrictions on 20 April, with subsequent lifting of some restrictions on 4 May and others planned for 5 June. Some activities are suspended until the end of the summer. Federal states have jurisdiction over some policy areas, so some regional differences have already emerged.
Federal and state governments have adopted a trigger threshold for imposing restrictions – more than 50 new infections per 100,000 habitants over a 7-day period. Subsequent outbreaks of COVID-19 have occurred in care homes, leading to a ban on visits to care homes and hospitals until 26 May. Three clusters involving staff at meat processing plants in three Federal States have also been reported; the date for lifting restrictions has been postponed and one plant has been closed until 17 May. A further cluster of infections occurred in refugee accommodation in Bavaria. On 10 May, the value of R rose to an estimated 1.1. This measure will be closely monitored to determine whether cases are increasing in a sustained way.
Childcare and educational settings
Pupils in the final year of primary and secondary school returned to classes on 4 May. The aim is that all pupils will return to school before the summer holiday. Universities were allowed to resume on 15 April.
Workplaces
Allowed to open, but workers are encouraged to work at home where possible.
Shops and markets
Shops of all sizes are now permitted to open. Access must be controlled with limits on capacity enforced.
Social and cultural venues
Restaurants and cafes may open, subject to appropriate distances between tables. Some museums and galleries can be re-opened depending on size. Individual states have the right to determine cinema and theatre openings.
Transport network
The transport network is running but face coverings or masks are mandatory.
Personal social activities
Weddings, baptisms and funeral gatherings are permitted for small groups.
Personal travel
Spending time in public spaces with one’s own household is permitted and meeting other people in public spaces is allowed subject to social distancing of 1.5 metres. Travel within Germany is permitted.
Mass gatherings
Events that attract large crowds such as concerts and festivals are prohibited until 31 August at the earliest.
Sport
Large sporting events are prohibited until 31 August. The top 2 football leagues can play matches from mid-May, but without spectators.
Religious worship
Permitted subject to social distancing.
Date lockdown started: 11 March
Date lockdown restrictions ease: 14 April
Estimate of total population infected: 4.65%
Modelling data estimates that the lockdown in Italy had an immediate impact on transmission, with R decreasing to below one within days.
The Government announced their phased approach to lifting restrictions on 10 April. Phase 2 of the implementation began on 4 May. No significant outbreaks have been reported since the latest restrictions were lifted. The next key dates for lifting restrictions are planned on a weekly basis from 18 May until mid-June (details below).
Childcare and educational settings
Exams in universities are permitted where social distancing and hygiene measures can be applied, or they may be done online. Schools (primary and secondary) will not resume classes until September.
Workplaces
Industrial, manufacturing and construction sectors and wholesale chains associated with them re-opened from 4 May.
Shops and services
Shops, beauty salons and hairdressers will be permitted to re-open from 18 May on a regional basis.
Social and cultural venues
From 4 May, bars and restaurants are permitted to offer takeaway services; regional rules mean that some may re-open from 18 May or 1 June. Parks and gardens re-opened from 4 May, with limits on gatherings; children’s play areas remain closed. Museums and libraries will re-open from 18 May. Cinemas and theatres will re-open from 15 June, pre-assigned seating with social distancing will be obligatory.
Transport network
Some airports reopened from 4 May. Face masks or other coverings are mandatory on all forms of public transport. Social distancing of 1 metre applies. The government is exploring whether installing plexiglas dividers could be used to increase passenger numbers.
Personal social activities
Funeral gatherings are permitted with up to 15 attendees.
Personal travel
Visits to family within one’s home region is permitted. Visits further afield remain prohibited unless for health or emergency reasons, or if visiting children who are staying with another main carer. Inter-region travel will be permitted from 3 June subject to epidemiological circumstances.
Sport
The public may exercise only in the vicinity of their homes, maintaining a distance of 2 metres. Professional and some amateur athletes are able to train individually behind closed doors from 4 May. Professional team training will be permitted from 18 May. Sports facilities such as gyms, swimming pools and leisure centres will re-open from 25 May. It is anticipated that professional football will resume from 13 June but this has not yet been approved.
Religious worship
Will be permitted from 18 May, subject to the capacity of buildings in line with social distancing. Face masks or other coverings are required.
Date lockdown started: 14 March
Date lockdown restrictions eased: 26 April
Estimate of total population infected: 5.59%
Modelling data estimates that the lockdown in Spain had an immediate impact on transmission, with R decreasing to below one within days.
The Government announced their phased approach to lifting restrictions on 28 April. Initial measures announced in phase 0 included allowing children and adults outside to exercise for one hour per day. Subsequent phases 1, 2 and 3 seek to lift a range of restrictions across multiple sectors. Each phase is expected to last for 2 weeks. Phase 1 begins from 4 May with subsequent phases expected to last until the end of June.
Childcare and educational settings
Academic settings expected to re-open in September. Some centres may be permitted to open earlier under certain circumstances, and with limits on capacity. For example, special education centres, infant schools for under 6s where both parents work and are unable to work remotely, or opening schools for pupils in their final year.
Workplaces
Agri-food and fisheries sectors can re-open. Other sectors will open later as they are not deemed essential in the first phase. In phase 3, protocols for reopening businesses will include use of PPE and other measures, including staggered working hours.
Shops and markets
In phase 1 shops may re-open (excluding shopping centres). Shops must limit capacity to 30%, 2 metres social distancing will apply and designated hours for over 65s. Phase 2 will permit shopping centres to open at 40% capacity, with no access to communal places or recreation zones. In phase 3, communal and recreational zones will open, with a 50% capacity limit.
Social and cultural venues
Cafes and restaurants may offer takeaway services and re-open terraces from 11 May, limited to 50% capacity. Hotels and tourist accommodation may also open in phase 1, but not communal spaces. In phase 2 hotel and catering premises will be allowed to open for table service, with a limit of 30% of capacity and adequate separation between tables.
Cinemas, theatres and auditoria
Cinemas, theatres and auditoria can re-open in phase 3 with a one-third capacity limit and using pre-assigned seats. Exhibitions, conference centres and monuments may also open with one-third capacity. In phase 3, activities that were at 30% capacity can increase to 50%.
Transport network
Social distancing measures will apply, for example on buses and trains the maximum seated capacity will be limited. In phase 1, local networks will operate at 80 to 100% of normal service levels, rising to 100% by phase 4, with limits on passenger occupancy. Long distance trains and buses will limit services on offer to 30% (with 50% occupancy). This service level could increase in phase 3 but no capacity figure is cited. Transport workers in direct contact with passengers must wear a face covering.
Personal social activities
Children and adults allowed to exercise outside for one hour per day from 26 April and 2 May respectively. From phase 1, limited social contact in groups for people not in a vulnerable group will be permitted. Subsequent phases will allow social contact in bigger groups, visits to second homes if they are in the same province and weddings with a limited number of attendees. Phase 3 will permit social contact for vulnerable people, with measures to protect them (these are unspecified in the government plan).
Sport
Sporting facilities for professional athletes can re-open, training for professional athletes permitted in phase 2. Professional championships will resume, with matches held without spectators or with limits on spectator numbers and can be broadcast.
Religious worship
Places of worship may open, with capacity limited to 30% in phase 1 and 50% in phase 2.
Date lockdown started: 23 January
Date lockdown restrictions ease: 8 April
The Chinese Government publishes daily situation reports on COVID-19. The Chinese government first reported no new locally transmitted infections on 19 March. Since lockdown restrictions were lifted, a new cluster of infections was reported in Wuhan and in the province of Jilin in early May. The media has reported that the Chinese Government intends to test the 11 million residents of Wuhan.
The Chinese Government has 4 phased measures, called response levels, which are enforced or lifted at provincial or city level according to local epidemiology.
Social and cultural venues
The limits on restaurants and bar openings have varied across regions, as have the limitations on opening municipal spaces such as parks.
Transport network and personal travel
Borders are closed to all except citizens, with returning residents required to enter quarantine for 14 days. Domestic travel restrictions have been extensive, with restrictions being lifted first in the provinces least affected. Public health measures on the transport network include fever observation checkpoints at train stations, airports and ports.
Personal social activities
Social distancing has varied across provinces with limitations on leaving home in some areas, while in others, people are asked to limit their interactions with others outside the home.
Sweden and South Korea have not adopted national lockdown policies like those described previously, but instead a combination of measures in both countries have led to R being suppressed to below 1. South Korea is returning to normal life and is now in the position of managing discrete outbreaks of disease. This situation, which will be faced by every country as they exit lockdowns or equivalent measures, is a test of national policy to contain new outbreaks to prevent a second wave of disease.
Date restrictions introduced: 10 March
In contrast with most European countries, Sweden has not imposed a general lockdown. It began measures specific to individual cases on 10 March, social distancing was encouraged on 16 March and a ban on public events was introduced on 29 March.
Estimate of total population infected: 4.06%
See the Swedish government’s national data COVID-19 data dashboard.
The impact of social distancing advice had a moderate impact on R, which dropped from just below 3 to approximately 2.5. The ban on public gatherings subsequently led R to decrease to below 1. Much debate has centred on Sweden’s decision not to impose a general lockdown, but instead to introduce selected public health measures that can be sustained over the long-term. The actions taken have reduced the R to less than 1, which is the principal aim of lockdown strategies. A report by Sweden’s public health agency has tracked the R value since mid-February; R has been at or below 1 since 18 April. However, there are questions about what the wider societal cost of this approach is, with criticism from Sweden’s scientific community as well in wider international discourse. Sweden’s public health agency estimated that one-third of Stockholm’s 1 million population had been infected by the beginning of May.
The government uses a 5-point scale to communicate risk – very low, low, moderate, high and very high. The current risk rating is very high.
Childcare and educational settings
Primary and junior schools are open, but high schools are closed.
Workplaces
Remain open.
Shops and markets
Remain open.
Social and cultural venues
Gatherings in cultural venues are limited to 50 people. Bars, cafes and restaurants remain open, as long as social distancing can be practised.
Transport network and travel
Non-essential travel to Sweden from countries outside the EU was banned on 17 March and applies until 15 May.
Personal social activities
From 1 April a national ban on visits to retirement homes is in force. Public gatherings of 50 people or more are also banned – such gatherings include demonstrations, religious gatherings, theatrical performances, and concerts.
Religious worship
Permitted, provided 50 people or fewer.
Date restrictions came into force: 1 March
Date restrictions ease: 20 April (phased easing until 5 May)
Following a period of 10 days with fewer than 10 cases or none at all each day, a new cluster of infections occurred in Seoul a few days after most restrictions were lifted. In this incident, 119 cases have been linked to one man with COVID-19 who visited a nightclub on 2 May. The authorities responded by ordering a temporary closure of nightclubs and bars.
The country has lifted all previous restrictions but has advised citizens to follow its distancing in daily life policy, applicable from 6 May. It states that distancing measures will be enhanced as required.
Childcare and educational settings
Schools re-opened from 13 May. Face coverings are obligatory.
Social and cultural venues
Theatres and similar venues will be re-opened shortly.
Sport
Professional sport is taking place without spectators. Other sporting facilities and venues will open later.
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What can deliberately infecting healthy people tell us about infectious diseases? How is this useful for developing treatments, and how do we manage the risks?
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