The long haul.

Via TPM:

16 March 2020 Imperial College COVID-19 Response Team

Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand

Summary

The global impact of COVID-19 has been profound, and the public health threat it represents is the most serious seen in a respiratory virus since the 1918 H1N1 influenza pandemic. Here we present the results of epidemiological modelling which has informed policymaking in the UK and other countries in recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number of public health measures – so-called non-pharmaceutical interventions (NPIs) – aimed at reducing contact rates in the population and thereby reducing transmission of the virus. In the results presented here, we apply a previously published microsimulation model to two countries: the UK (Great Britain specifically) and the US. We conclude that the effectiveness of any one intervention in isolation is likely to be limited, requiring multiple interventions to be combined to have a substantial impact on transmission.

Two fundamental strategies are possible: (a) mitigation, which focuses on slowing but not necessarily stopping epidemic spread – reducing peak healthcare demand while protecting those most at risk of severe disease from infection, and (b) suppression, which aims to reverse epidemic growth, reducing case numbers to low levels and maintaining that situation indefinitely. Each policy has major challenges. We find that that optimal mitigation policies (combining home isolation of suspect cases, home quarantine of those living in the same household as suspect cases, and social distancing of the elderly and others at most risk of severe disease) might reduce peak healthcare demand by 2/3 and deaths by half. However, the resulting mitigated epidemic would still likely result in hundreds of thousands of deaths and health systems (most notably intensive care units) being overwhelmed many times over. For countries able to achieve it, this leaves suppression as the preferred policy option.

We show that in the UK and US context, suppression will minimally require a combination of social distancing of the entire population, home isolation of cases and household quarantine of their family members. This may need to be supplemented by school and university closures, though it should be recognised that such closures may have negative impacts on health systems due to increased absenteeism. The major challenge of suppression is that this type of intensive intervention package – or something equivalently effective at reducing transmission – will need to be maintained until a vaccine becomes available (potentially 18 months or more) – given that we predict that transmission will quickly rebound if interventions are relaxed. We show that intermittent social distancing – triggered by trends in disease surveillance – may allow interventions to be relaxed temporarily in relative short time windows, but measures will need to be reintroduced if or when case numbers rebound. Last, while experience in China and now South Korea show that suppression is possible in the short term, it remains to be seen whether it is possible long-term, and whether the social and economic costs of the interventions adopted thus far can be reduced.

Transmission events occur through contacts made between susceptible and infectious individuals in either the household, workplace, school or randomly in the community, with the latter depending on spatial distance between contacts. Per-capita contacts within schools were assumed to be double those elsewhere in order to reproduce the attack rates in children observed in past influenza pandemics. With the parameterisation above, approximately one third of transmission occurs in the household, one third in schools and workplaces and the remaining third in the community. These contact patterns reproduce those reported in social mixing surveys.

We assumed an incubation period of 5.1 days. Infectiousness is assumed to occur from 12 hours prior to the onset of symptoms for those that are symptomatic and from 4.6 days after infection in those that are asymptomatic with an infectiousness profile over time that results in a 6.5-day mean generation time. Based on fits to the early growth-rate of the epidemic in Wuhan we make a baseline assumption that R0=2.4 but examine values between 2.0 and 2.6. We assume that symptomatic individuals are 50% more infectious than asymptomatic individuals. Individual infectiousness is assumed to be variable, described by a gamma distribution with mean 1 and shape parameter =0.25. On recovery from infection, individuals are assumed to be immune to re-infection in the short term. Evidence from the Flu Watch cohort study suggests that re-infection with the same strain of seasonal circulating coronavirus is highly unlikely in the same or following season (Prof Andrew Hayward, personal communication).

Infection was assumed to be seeded in each country at an exponentially growing rate (with a doubling time of 5 days) from early January 2020, with the rate of seeding being calibrated to give local epidemics which reproduced the observed cumulative number of deaths in GB or the US seen by 14th March 2020.

In total, in an unmitigated epidemic, we would predict approximately 510,000 deaths in GB and 2.2 million in the US, not accounting for the potential negative effects of health systems being overwhelmed on mortality.

For an uncontrolled epidemic, we predict critical care bed capacity would be exceeded as early as the second week in April, with an eventual peak in ICU or critical care bed demand that is over 30 times greater than the maximum supply in both countries (Figure 2).

The aim of mitigation is to reduce the impact of an epidemic by flattening the curve, reducing peak incidence and overall deaths (Figure 2). Since the aim of mitigation is to minimise mortality, the interventions need to remain in place for as much of the epidemic period as possible. Introducing such interventions too early risks allowing transmission to return once they are lifted (if insufficient herd immunity has developed); it is therefore necessary to balance the timing of introduction with the scale of disruption imposed and the likely period over which the interventions can be maintained. In this scenario, interventions can limit transmission to the extent that little herd immunity is acquired – leading to the possibility that a second wave of infection is seen once interventions are lifted[.]

Given that mitigation is unlikely to be a viable option without overwhelming healthcare systems, suppression is likely necessary in countries able to implement the intensive controls required. Our projections show that to be able to reduce R to close to 1 or below, a combination of case isolation, social distancing of the entire population and either household quarantine or school and university closure are required (Figure 3, Table 4). Measures are assumed to be in place for a 5-month duration. Not accounting for the potential adverse effect on ICU capacity due to absenteeism, school and university closure is predicted to be more effective in achieving suppression household quarantine. All four interventions combined are predicted to have the largest effect on transmission (Table 4). Such an intensive policy is predicted to result in a reduction in critical care requirements from a peak approximately 3 weeks after the interventions are introduced and a decline thereafter while the intervention policies remain in place. While there are many uncertainties in policy effectiveness, such a combined strategy is the most likely one to ensure that critical care bed requirements would remain within surge capacity.

Once interventions are relaxed (in the example in Figure 3, from September onwards), infections begin
to rise, resulting in a predicted peak epidemic later in the year. The more successful a strategy is at
temporary suppression, the larger the later epidemic is predicted to be in the absence of vaccination,
due to lesser build-up of herd immunity.

Overall, our results suggest that population-wide social distancing applied to the population as a whole would have the largest impact; and in combination with other interventions – notably home isolation of cases and school and university closure – has the potential to suppress transmission below the threshold of R=1 required to rapidly reduce case incidence. A minimum policy for effective suppression is therefore population-wide social distancing combined with home isolation of cases and school and university closure.

To avoid a rebound in transmission, these policies will need to be maintained until large stocks of vaccine are available to immunise the population – which could be 18 months or more. Adaptive hospital surveillance-based triggers for switching on and off population-wide social distancing and school closure offer greater robustness to uncertainty than fixed duration interventions and can be adapted for regional use (e.g. at the state level in the US). Given local epidemics are not perfectly synchronised, local policies are also more efficient and can achieve comparable levels of suppression to national policies while being in force for a slightly smaller proportion of the time. However, we estimate that for a national GB policy, social distancing would need to be in force for at least 2/3 of the time (for R0=2.4, see Table 4) until a vaccine was available.

However, there are very large uncertainties around the transmission of this virus, the likely effectiveness of different policies and the extent to which the population spontaneously adopts risk reducing behaviours. This means it is difficult to be definitive about the likely initial duration of measures which will be required, except that it will be several months. Future decisions on when and for how long to relax policies will need to be informed by ongoing surveillance.

Perhaps our most significant conclusion is that mitigation is unlikely to be feasible without emergency surge capacity limits of the UK and US healthcare systems being exceeded many times over. In the most effective mitigation strategy examined, which leads to a single, relatively short epidemic (case isolation, household quarantine and social distancing of the elderly), the surge limits for both general ward and ICU beds would be exceeded by at least 8-fold under the more optimistic scenario for critical care requirements that we examined. In addition, even if all patients were able to be treated, we predict there would still be in the order of 250,000 deaths in GB, and 1.1-1.2 million in the US. In the UK, this conclusion has only been reached in the last few days, with the refinement of estimates of likely ICU demand due to COVID-19 based on experience in Italy and the UK (previous planning estimates assumed half the demand now estimated) and with the NHS providing increasing certainty
around the limits of hospital surge capacity.

We therefore conclude that epidemic suppression is the only viable strategy at the current time. The social and economic effects of the measures which are needed to achieve this policy goal will be profound. Many countries have adopted such measures already, but even those countries at an earlier stage of their epidemic (such as the UK) will need to do so imminently.

Our analysis informs the evaluation of both the nature of the measures required to suppress COVID-19 and the likely duration that these measures will need to be in place. Results in this paper have informed policymaking in the UK and other countries in the last weeks. However, we emphasise that is not at all certain that suppression will succeed long term; no public health intervention with such disruptive effects on society has been previously attempted for such a long duration of time. How populations and societies will respond remains unclear.

Science. Data.

We need more hospital beds, more equipment, more isolation, more leadership. And a vaccine that works, pretty damn quick.

It’s going to be a really long haul.