Why have deaths from COVID-19 plateaued in Europe? Is this due to herd immunity?
Transmission of SARS-CoV-2 appears to be in marked decline in many countries in Europe, North America and parts of Asia. This follows unprecedented governmental interventions, which have aimed to reduce travel and physical contact between individuals.
An interesting correspondence in The Lancet written by Lucy C Okell and others published 11 June 2020 suggests that there are two possible and very different explanations for this decline.
- Lockdown, social distancing and other interventions
They argue that this would imply that the pandemic is still at a relatively early stage and that a large proportion of the population still remain susceptible. With this scenario, there is clearly a high risk of renewed transmission when interventions or behavioural modifications are relaxed. This explanation is also consistent with the high infection fatality ratio, IFR, in order to explain the number of deaths which have occurred.
- Herd Immunity
The observed declines in cases and deaths could be due to the achievement of herd immunity. This would imply that a large proportion of the population are indeed now protected from infection. This would be either through the acquisition of immunity following previous infection or through other natural means such as cross protection from other coronaviruses.
Under this scenario, it would be expected that there would be further declines in cases and deaths even in the absence of interventions or behavioural modifications. If one assumes that a large proportion of the population has been infected, this explanation implies a very low IFR to explain the number of deaths that have occurred to date.
In order to formulate plans on social distancing and travel restrictions it is important to identify, which explanation is correct. It is also important when considering subsequent public health responses aimed at reducing morbidity and mortality, especially within the context of the economic and health impacts of COVID-19 mitigation and suppression strategies.
Lucy Okell and others took a data-driven approach to establish which of these explanations is better supported by data. They based their arguments by looking at trends in cumulative deaths over different times in a number of countries, which went into lockdown at different stages during the pandemic. They also investigated data obtained from serological studies on the proportion of the population that had evidence of prior infection.
They found that there was little evidence to support the explanation, which relied on herd immunity. Under herd immunity the cumulative mortality rate due to COVID-19 per million of the population would be expected to plateau at roughly the same level in different countries. This was not what the data showed. It is highly unlikely that differences in mortality reporting across countries would explain the scale of variation.
If acquisition of herd immunity was responsible for the drop in incidence in all countries, then disease exposure, susceptibility or severity would need to be extremely different between these three populations. However, these countries have similar demographics, close geographic proximity, strong genetic similarities, robust health systems, and probably similar previous exposure to other human coronaviruses. There is therefore little evidence to support herd immunity.
In contrast, if the levelling of deaths is caused by interventions and associated behavioural changes, then these discrepancies can be explained by the timing and stringency of interventions relative to the introduction of the virus.
It is clear that countries which went into lockdown early experienced fewer deaths in subsequent weeks. They looked at countries which applied strict suppression measures and compared the per-capita deaths at the time of lockdown with the per-capita deaths in the following six-week period. If herd immunity had already been reached, it would be expected that there was no correlation or even a negative correlation as lockdown would not alter the herd immunity threshold in the population or the ultimate death rate per capita. They found a strong linear trend, which suggested that countries which went into lockdown early definitely experienced fewer deaths in the following six-week period. This is inconsistent with the herd immunity explanation. It is however exactly what one would expect under the explanation of lockdowns curtailing transmission and deaths.
Thus stringent suppression measures are most effective when pre-lockdown transmission is low.
Finally, there exists a strong and consistent relationship between the prevalence of antibodies to SARS-CoV-2 and mortality from COVID-19 in European populations. They compared the proportion of the population that had evidence of previous infection as measured by antibodies at a given time point with the proportion of the population that died from COVID-19 up to the same time point. They found a strong linear relationship between seroprevalence, that is antibodies and evidence of previous infection, and mortality, which indicated the disparate regions have experienced a similar mortality per infection.
This result is important. It shows that if herd immunity had been reached because of a large proportion of the population being infected, then one would have expected to see a higher seroprevalence, i.e. evidence of previous infection and a correspondingly lower slope equivalent to a lower IFR. The current data in Europe is consistent with an IFR which is many times higher than seasonal influenza.
One could consider that differences between the European country data is caused by differences in disease severity or death reporting. If this were the case, then one would expect to see very different slopes between countries. The data did not support this explanation. If herd immunity had been reached in all regions, then one would expect to see relatively little variation in seroprevalence, that is evidence of previous infection.
If one looks at Spain as an example if the country were to have achieved herd immunity, one would expect that the threshold would differ by a factor of ten between regions. In contrast, all of these patterns are easily explained if one assumes that interventions are acting to keep deaths and infections at pre-herd immunity levels. This implies that Denmark and Spain have a broadly similar infection fatality ratio, but that Denmark had fewer deaths and lower seroprevalence because the epidemic did not progress as far as it did in Spain before lockdown came into place.
Evidence from outbreaks in confined settings shows that the proportion of individuals infected can reach high levels more than 60%. This provides little reason to think that people in these countries who are currently seronegative are not susceptible to infection.
Summarising, there appear to be large differences in the pattern of per-capita deaths in different countries, which are difficult to reconcile with herd immunity arguments. They are however easily explained by the timing and stringency of interventions. Seroprevalence studies also provide an independent source of information that is highly consistent with mortality data. The herd immunity argument is therefore at odds with both mortality and seroprevalence data, whereas the intervention argument provides an explanation for both.
Although the impacts of current control interventions on transmission clearly need to be balanced against their short-term and long-term economic and health impacts on society, the epidemiological data suggest that no country has yet seen infection rates sufficient to prevent a second wave of transmission. It is therefore important that controls or behavioural precautions need to be relaxed with compensatory measures in place.
The London General Practice understands the need for the relaxation of lockdowns and restrictions. However, it argues that these should be done in a moderate and considered way.
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