A scientist’s opinion: Interview with Dr Deepti Gurdasani about SARS-CoV-2 mutations

Deepti GurdasaniDr Deepti Gurdasani ’s background is as a clinical epidemiologist and statistical geneticist. After completing her clinical training in internal medicine at Christian Medical College, Vellore, India, she completed her MPhil in epidemiology and biostatistics at the University of Cambridge in 2010, followed by a PhD examining genetic factors associated with disease in genetically diverse populations, including genetic factors associated with severe influenza and virus control in HIV infection. Her subsequent work has focused on global health, specifically using complex statistical methods to understand social, clinical and genetic risk factors associated with disease in diverse populations across the globe. Her current focus is on understanding the impact of different interventions, as well as environmental, social and geographical factors, on the COVID-19 pandemic in a global context.

Does the new SARS-CoV-2 variant have a higher propensity to infect children?

The current evidence suggests that the new SARS-CoV-2 B.1.1.7 variant, or the so-called UK variant, has spread uniformly across all age groups and increases transmissibility of the virus across all ages. Although initial evidence showed a higher prevalence among children in England, this is likely to have been a result of an early spread of the variant at a time when schools were open but the region was in lockdown, with restrictions in place across the UK. But the spread appears uniform now, suggesting that children do not have special susceptibility to the variant, but that the variant is 30-70% more transmissible across all age groups.

Since children have been a major source of transmission, especially while schools are open, this increased transmissibility is concerning, and makes the need for mitigatory measures in schools all the more urgent. During the previous lockdown in England, while schools were open the new variant was spreading with an R value of 1.45, suggesting a difficulty in controlling community spread even with restrictions in place. This means we need to consider all measures, including curbing transmission within the school environment. This means use of masks, social distancing, smaller class sizes, use of large empty spaces, attention to ventilation, and ventilation monitoring.

In your opinion, can there be cross-reactivity against SARS-CoV-2 in the current COVID-19 vaccines, and if so, can we expect them to be effective against new coronaviruses, mutations and other diseases in the future?

Early results from the laboratory suggest high levels of neutralisation against the B.1.1.7 variant (the UK variant) with antibodies directed at previous variants. However, concerningly, Public Health England has reported the emergence of further mutations in this variant, including the E484K mutation, which has recently shown a degree of immune escape from sera of people vaccinated with the previous variant of virus.

Recent data from Johnson & Johnson and Novavax vaccine trials have also shown reduced effectiveness in South Africa, potentially as a result of the variant circulating there, which also carries the E484K mutation. This variant has also been identified in the UK, even in cases not linked directly to travel.

All this raises concerns about whether infection from previous variants, or vaccine immunity directed at previous variants, will confer the same degree of protection against new variants. We do expect a high degree of protection, but this may be reduced. It is clear that allowing the virus to adapt by allowing high levels of transmission to continue is a risk which may have long-term consequences for pandemic control. The only way to prevent this is to follow elimination strategies, to prevent transmission altogether, as several countries have done.

In your opinion, could (re-)infection be associated with mutations?

There are concerns that variants that have the E484K mutation (for example, the so-called South Africa variant, the Manaus variant in Brazil and most recently adaptations of the UK variant as well) may not be neutralised completely by antibodies directed at previous variants. Although early data do not suggest an increased risk of re-infection from the South Africa variant, we do need to wait for adequate follow-up time to be able to evaluate this with a high degree of certainty.

It is likely that vaccines will have a high level of effectiveness even against these variants, but this may be reduced to an extent. Recent studies of neutralisation of viruses with specific mutations by post-vaccine sera from people vaccinated with the Pfizer vaccine showed a modest reduction in neutralisation of a virus with selected mutations. However, these studies did not directly examine the variant and all its mutations, and did not examine this specifically among elderly groups, where this escape might be even more concerning. This is why many manufacturers are in the process of developing boosters directed against new variants, but this is likely to take time.

The Zero-COVID Strategy urges European countries to cooperate with each other. In your letter – together with more than 300 scientists – you call for European countries to work together to eliminate the virus. Do you envisage that the Zero-COVID Strategy will be adopted by European governments?

It is clear that half-way measures to contain the spread do not work – they lead to prolonged and repeated lockdowns, and devastating impacts on public health and the economy. The recent variants that have arisen in different parts of the world highlight the gamble we take when we allow high levels of transmission to continue which favour virus adaptation in ways we cannot fully predict or respond to quickly. Countries that have followed zero-COVID strategies have protected public health, and the economy, and returned to near-normal life. Their vaccine resources are not at risk from virus adaptation or new mutations.

It has been really encouraging to see discussions about a zero-COVID approach within the German government. I hope other countries also follow.

I think many European countries have used a short-sighted pandemic strategy. There has been a false dichotomy created between public health and the economy, ignoring all real-world evidence that suggests that the best way to protect the economy, society and public health is to control COVID. A longer-term approach is needed to prevent a repeat of previous failures, which would lead to countries being stuck in endless cycles of lockdowns with their devastating impacts.

The Zero-COVID strategy, depending on the measures implemented, may take 3-5 months to fully implement, depending on the initial case numbers in a given country.

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