How can we get our population back to work? What do our policy makers in Government need to know about the COVID-19 immunity?
A third of the world is still under lockdown as public health measures have been used to reduce the spread of COVID-19 caused by the SARS-CoV-2 virus.
Our Government officials are increasingly being asked to discuss the rationales and strategies for moving out of lockdown.
This process of re-emergence has already cautiously started in Austria, Switzerland, Denmark, Wuhan and some US states.
It is essential that our Government officials and ministers have the best possible data in order to counterpoise the balance between further disease spread and socioeconomic costs.
Various countries have a strategy which aims to stagger the return to work on the basis of disease severity, risk and age. This does not take into account how exposing even lower risk individuals such as young people with no other diseases, to the virus and increasing the so called herd immunity, can still result in a pandemic spread.
The only way to stop SARS-CoV-2 transmission is to stop it’s spread.
How to move out of lockdown, the lynchpin for the strategy appears to:
- Rest on increased testing and contact tracing
- Possible return to work permits based on immune status
- New effective treatments
This is a broadly sensible approach, but immunology (in relation to COVID-19) is a complex subject as I believe our Government ministers are aware.
At present it is not known whether antiviral protection correlates with immunological status or the proportion of a population who must attain it. This makes it impossible to identify when a level of immunity has been reached in the population.
There has been much discussion that scaling up antibody tests will determine who is immune and therefore give an indication of the extent of herd immunity, thus helping to indicate who could re-enter the workforce.
However, there are many questions to address including:
- The accuracy of tests
- The practicalities of implementation of laboratory based versus home use assays
- Crucially, for any country who is contemplating this, how solid the assumption is that antibodies to the SARS-CoV-2 spike protein equate with functional protection.
Furthermore, if presence of these antibodies is protective, how can it be decided what proportion of the population requires these antibodies to mitigate subsequent waves of COVID-19.
Caution is needed because the total measureable antibody is not precisely the same as a protective virus neutralising antibody.
It has been found in studies that 10 to 20% of symptomatically infected people have little or no detectable antibody. It has been found in some cases of COVID-19 that a low virus binding antibody correlated with lethal or near lethal infection or conversely with having a mild infection with little antigenic stimulation.
It is essential that our scientists identify the correlates of protection but have a robust understanding of how this correlates with progression to severe COVID-19. In order to ascertain certainty on the degree of immunity, studies will require evidence probably in non-human primate models as was used in the studies of Ebola virus.
As has been mentioned in previous reviews, studies of survivors of SARS showed that about 90% had functional virus neutralising antibodies and around 50% had a strong T-cell response. This helps to bolster confidence that most survivors of severe COVID-19 would be expected to have protective antibodies. However, most of these studies either of the SARS survivors or within COVID-19 patients were performed on people who were hospitalised and had severe symptomatic disease.
Data is urgently needed for individuals with SARS-CoV infection who have not been hospitalised.
Another question, how long is immunity to COVID-19 likely to last?
This is unclear. A good estimate comes from the closely related coronaviruses which suggests that although immunity might wane, antibodies are detectable beyond one year following hospitalisation.
This provides little comfort as there is a possibility that there will be another wave of COVID-19 cases in three or four years’ time.
However, specific T lymphocyte immunity within MERS subjects were found which was detectable for four years, considerably longer than an antibody response.
This uncertainty about COVID-19 and immunity must be addressed and this could happen by monitoring the frequency of re-infection with the SARS-CoV-2.
Caution needs to be exercised with reports from China and South Korea as those individuals who seem to have cleared the virus tested negative on PCR might have harboured persistent virus. Virus sequencing studies will help to resolve this issue.
If one looks at seroprevalence data, this can help to show the proportion of a population which has been exposed to and is potentially immune to the virus. This can then be used to determine how much herd immunity is sufficient to mitigate subsequent substantial outbreaks of COVID-19. This of course depends on many variables, but a calculation suggests that at least 60% of the population would need to have protective immunity either by natural infection or vaccination.
From the available COVID-19 data derived from patients who were hospitalised with severe infection, it would appear that around 90% have developed IgG antibodies within the first two weeks of symptomatic infection and this appears to coincide with the disappearance of the virus.
However, we need to test those non-hospitalised individuals who have either milder disease or no symptoms to understand their antibody status.
Anecdotal evidence appears to suggest that under 10% of tested controls have developed specific IgG antibodies. It would therefore appear that a natural exposure during the pandemic in the short to medium term will not deliver the required level of herd immunity and there will therefore need to be a substantial mass vaccination programme.
There are over 100 COVID-19 vaccinations in development with some soon to be in phase one trials to assess safety and immunogenicity. These various trial vaccines encompass different platforms:
- Differences in the potency with which immunity is stimulated
- The specific immune mediators which are mobilised
- The number of required boosts
- Durability of protection
- Possibility of production and supply chains
Clearly safety evaluation of these vaccines will need to be of a high standard.
Some features of the immune response induced by infection, such as high concentrations of Interleukin-6 and tumour necrosis factor which are elicited by some of these candidate vaccines, are identified as biomarkers of severe outcome.
However, researchers must be commended as they have brought us to a point where there are many candidate vaccinations in development against a novel virus which was only first sequenced in January 2020.
Some may feel that the delivery of a vaccine which is efficacious is a competition with a race to the finish. However, a considered evaluation of a safe potent global vaccine is required.
Science will have to guide the clinical therapeutic approach for an infected person. It will also have to guide policy decisions.
Policy decisions and policy makers will need to be led by comprehensive seroprevalence data and a solid research based grasp of protection, which hopefully will give an evidence base to herd immunity rather than optimistic guesses.
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