Covid-19: Infections climb globally as EG.5 variant gains ground

Small waves

Covid hospital admissions in the US are up 40% from the lows seen in June, and covid admissions in England rose 76% from 21 July to 4 August. But the overall numbers in both countries are still low compared with previous peaks and even to most of the troughs during the pandemic. The past week saw 10 320 covid admissions in the US, compared with 150 674 at the height of the third wave in January 2022.

The only country experiencing case numbers comparable with previous waves is South Korea, where daily new cases reached 65 000 last week. But this fourth wave is South Korea’s smallest yet, in both cases and deaths, and appears now to have peaked.

New Zealand has the greatest density of new covid cases after South Korea, but on 15 August it dropped its last pandemic restrictions, removing requirements to isolate for seven days and to wear masks in hospitals.

WHO last week raised the classification of EG.5 and its sublineages from “variant under monitoring” to “variant of interest,” a designation it shares with BA.2.75, which has not proliferated, and with XBB.1.5. No variant currently meets the criteria to be a “variant of concern.” WHO estimates the current public health risk from all these variants, including EG.5, as “low.”

FLip threat

Experts warn, however, of a future threat from mutations seen in EG.5, also found in some rarer variants of the XBB.1.5 family and other lineages, which can help the virus bind to cell receptors and reduce the number of antibodies the immune system produces to fight it.

The L455F and F456L mutations are nicknamed FLip mutations because they switch the positions of two amino acids on the spike protein labelled F and L. These mutations were predicted months ago as a likely consequence of the widespread use of monoclonal antibodies to treat covid.

The EG.5 variant descends from and resembles the still circulating XBB.1.9.2 subvariant, but with the addition of one FLip mutation, F456L. Its subvariant EG.5.1 carries a further spike mutation called Q52H. The role played by Q52H is still unclear, but it appears to boost potency, as this subvariant has already overtaken its progenitor.

The EG.5 lineage accounts for 49.1% of the circulating virus with one or both FLip mutations, according to WHO’s risk assessment. But there are now more than 20 subvariants of XBB and of other lineages that also carry FLip mutations. These include subvariants of XBB that carry both FLip mutations which, in laboratory testing, outperformed EG.5.1 at capturing cells and evading immune response. These XBB+L455F+F456L subvariants, yet to be assigned numbers, account for a small but rising number of cases.

“This certainly suggests this evolution of the virus will be more troubling than EG.5.1 and we can expect it to show further growth advantage in the weeks ahead,” wrote Eric Topol, of Scripps Research in California, in an analysis of the FLip threat.

“To be clear, we are not looking at an ‘omicron event’ now, whereby there will be a dramatic increase in transmission and adverse outcomes because of a boatload of new mutations,” wrote Topol. But the new changes “are a signal that there’s more to come with SARS-CoV-2.”6

New vaccines

New versions of the Moderna, Novavax, and Pfizer boosters, expected in the coming weeks, were designed to work against XBB.1.5, a close cousin of EG.5’s ancestor XBB.1.9.2. They are expected to offer better protection than existing vaccines against the EG.5 lineage. Antiviral drugs like nirmatrelvir/ritonavir (Paxlovid) also remain effective.

“Right now, viruses are still susceptible to our vaccine, they’re still susceptible to our medicines, they’re still picked up by the tests,” said CDC director Mandy Cohen. “So all of our tools still work as the virus changes.”