If you thought Covid-19 was dead and gone, think again. Early signs indicate that the UK may be at the start of a new wave of Covid infections driven by BA.4 and BA.5 – while new data suggests these variants may have evolved to refavour infecting lung tissue, which could make them more dangerous.
So what can we expect in the coming weeks and months?
Although BA.2 continues to account for the bulk of UK infections, data from the Office for National Statistics up to 2 June suggests that Covid cases may be starting to rise again in England and Northern Ireland, driven by an increase in BA.4 and BA.5 infections. The trends were uncertain in Wales and Scotland.
Also gaining ground in the UK are BA.5.1 (a child of BA.5), and the BA.2.12.1 subvariant (the USA’s dominant Covid strain), which the UK Health Security Agency is monitoring.
BA.4 and BA.5 were officially designated variants of concern (VOC) in the UK on 20 May, having first been detected in South Africa during January and February of this year.
According to the latest ONS data, about one in 70 people in England were estimated to have Covid in the week leading up to 2 June. In Northern Ireland it was about one in 65, in Wales about one in 75 and in Scotland about one in 40.
In South Africa, BA.4 and BA.5 have been responsible for a second wave of Omicron infections beginning at the start of May, which now appears to be flattening off. However, South Africa wasn’t hit by the highly transmissible BA.2 variant in the same way the UK was, and scientists had hoped that high levels of immunity from recent infection with BA.2 and booster vaccines might be enough to prevent these newer variants from gaining a significant foothold here.
However, with immunity from third vaccine doses waning in most population groups, and only the over-75s, and extremely vulnerable groups having been offered “spring booster” doses, this cannot be guaranteed. Neither is recent infection with the BA.1 or BA.2 Omicron variants necessarily protection against reinfection with BA.4 or BA.5.
According to research published in Science on Tuesday, natural infection with Omicron doesn’t produce a strong immune response, regardless of whether scientists look at antibodies or T-cells – meaning that people who have already recovered from an Omicron infection can quickly become reinfected. The findings, from Prof Danny Altmann at Imperial College London and colleagues, may help to explain why infection levels have remained high in countries such as the UK, despite so many already having been infected with it.
According to preliminary data from Kei Sato at the University of Tokyo and colleagues, BA.4, BA.5 and BA.2.12.1 may have evolved to refavour infection of lung cells, rather than upper respiratory tract tissue – making them more similar to earlier variants, such as Alpha or Delta. The propensity of earlier Omicron variants to prefer infecting non-lung tissue may be one reason why infections tend to be milder in most people.
“It looks as though these things are switching back to the more dangerous form of infection, so going lower down in the lung,” Dr Stephen Griffin, a virologist at the University of Leeds, said.
Sato’s experiments indicate that BA.4, BA.5 and BA.2.12.1 replicate more efficiently in human lung cells than BA.2, while further experiments in hamsters suggest that BA.4 and BA.5 may cause more severe disease.
These variants also appear to have a higher reproduction number than BA.2, while further experiments by Sato’s lab indicate that BA.4 and BA.5 may be resistant to immunity induced by earlier Omicron infections (similar to Altmann’s findings).
“Altogether, our investigations suggest that the risk of [these] Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2,” Sato said.
It also put paid to the idea that the virus is on the verge of merely turning into common cold. “It clearly isn’t, and there’s no pressure on it to do that, really,” said Griffin.
Even so, the rise of BA.4/5 and other subvariants by no means puts us back to square one. The UK’s population is, by and large, highly vaccinated, and previous infection with other variants will also count for something. Those who haven’t been vaccinated remain vulnerable, however.
Prof Tulio de Oliveira, the director of the Centre for Epidemic Response and Innovation at Stellenbosch University in South Africa, pointed out that the BA.4/5 wave has been less deadly than any of the previous waves to have hit his country. In part, this could be because hospital Covid wards were largely empty when it started, but it is also probably the result of high levels of population immunity.
However, hospitalisations and deaths are only part of the picture. Long Covid cases continue to rise in the UK. According to the latest ONS data, 2 million people in the UK are thought to be living with long Covid – the highest figure since official surveys began.
So, what to do about it? Data on the efficacy of boosters against these newer subvariants is still lacking, but if previous experience is anything to go by, they are likely to largely reinstate immune protection – at least against hospitalisation and death. A fourth dose is expected to be offered to the over-65s, frontline health and social care workers, care home residents and staff, and clinically vulnerable people from the autumn.
With luck, BA.4 and BA.5 will present just a minor blip in the UK’s transition out of the Covid crisis. But their emergence is a reminder that smooth sailing is by no means guaranteed.
