The Omicron descendant EG.5 is the latest to be labeled a "variant of concern" by the World Health Organization (WHO), joining the current ranks of XBB.1.16 and XBB.1.5. The new designation, made as part of an initial risk assessment of the variant on August 9, reflects its "notable increase" in global prevalence over recent weeks.
The report comes as the U.S. is experiencing a rise in hospitalizations and deaths and anticipation grows for updated vaccines , which are expected to be available this fall. The EG.5 variant could contribute to an increase in cases, the report noted, although there is no evidence to date that it causes more severe disease.
For now, the report concludes, the new variant does not appear to represent a greater risk to public health than others that are circulating. That said, he cautions that currently, variant surveillance is not representative and variant reporting is unreliable . These factors are creating data gaps, a barrier to comprehensive EG risk assessment.5.
Here’s what is currently known about the variant and how it could shape the COVID-19 situation in the coming months.
Has a growth advantage
The WHO risk assessment determined that EG.5 has a moderate growth advantage. The variant was first reported to the WHO in February, and its percentage of reported sequences has steadily increased since then. Its global prevalence more than doubled this summer, from around 8% in the week ending June 25 to around 17% in the week ending July 23.
It was not yet rising globally at the time of publication, according to the most recent data available. A WHO epidemiological update on August 10 noted that XBB.1.16 was the most prevalent variant worldwide during the week ending July 23, accounting for a quarter of virus sequences. XBB.1.5 was in decline, accounting for about 13% of the sequences.
But EG.5.1, a subvariant that represents the majority of EG.5 sequences, has a higher effective reproduction number than those XBB variants, according to a study posted on the preprint server bioRxiv, which has not yet been reviewed by peers. This finding suggests that EG.5 and its sublineages could predominate "in the near future," virologist Kei Sato, PhD, lead author of the study and professor at the Institute of Medical Sciences at the University of Tokyo in Japan, wrote in a paper. email to JAMA.
EG.5 is already the fastest growing variant in several areas of the world. In the US, it and its sublineages likely surpassed both XBB.1.16 and XBB.1.5 in early August, according to projections from the Centers for Disease Control and Prevention (CDC).
Has antibody escape properties
EG.5 descends from XBB.1.9.2, an Omicron offspring with the same spike protein as XBB.1.5, the variant targeted by upcoming vaccines. But unlike those variants, EG.5 has the F456L spike protein mutation, which in laboratory experiments allowed it to evade most of XBB.1.5’s neutralizing antibodies. The EG.5.1 subvariant, which represents 88% of the available EG.5 sequences, contains an additional spike protein mutation, Q52H.
The F456L mutation appears to be especially important, Sato and others said. "F456L in particular has shown up repeatedly in the descendants of XBB.1.5 and may make it slightly less susceptible to antibodies in previously vaccinated and/or infected people," Nicole Doria-Rose, PhD, staff scientist at the National Institutes of Health (NIH) said in an email. F456L may also be related to transmissibility, said Doria-Rose, head of the Humoral Immunology Core at the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases.
Based on current data, the WHO has classified the risk of antibody escape from EG.5 as moderate . The report cautioned, however, that the immune escape results are based on single-laboratory studies using pseudotyped, not wild-type, viruses, and that additional experiments are needed to further evaluate how well EG.5 thwarts the virus. existing antibodies.
It is unclear if it is driving the COVID wave
In the US, COVID-19 test positivity, wastewater levels, emergency department visits, hospitalizations and deaths are increasing , according to CDC data through the first week of August . However, it is unclear to what extent EG.5 might be driving the current wave. Sato said waning immunity from vaccines and previous infections could be contributing.
It’s also important to note that hospitalizations and deaths in the U.S. remain drastically lower than this time last year. Carlos del Rio, MD, a distinguished professor of medicine in the Division of Infectious Diseases at Emory University School of Medicine and president of the Infectious Diseases Society of America, said he is "somewhat concerned" about the current rise in hospitalizations, which he attributes mainly to XBB Variants. “However,” he wrote in an email, “I also know that, if people receive a booster , it is very unlikely that they will end up hospitalized when they become infected.”
There is no indication that it is more serious
There are so far no reports of EG.5 causing more severe cases of COVID-19, prompting the WHO to classify its risk level for severe disease as low .
“Several countries with increasing prevalence of EG.5 have seen increases in cases and hospitalizations, although there is currently no evidence of an increase in disease severity directly associated with EG.5,” the report noted.
Doria-Rose explained that EG.5 could be related to the current increase in COVID-19 cases and therefore hospitalizations, “based on its transmissibility , not its severity.”
However, there are warnings in the WHO risk assessment. Global reports of new hospitalizations and intensive care unit admissions have dropped substantially, so the WHO said it is best to be cautious when interpreting data on severe cases. And he said more studies are needed to investigate the variant’s effect on clinical outcomes.
There is optimism about the updated vaccine booster
The updated COVID-19 vaccines are expected to be available in the US in mid- to late September, assuming they receive authorization from the US Food and Drug Administration (FDA) and are recommended by CDC, an FDA spokesperson told JAMA in an email. The big question is, will they be effective against EG.5?
Both del Rio and Doria-Rose said they believe the XBB.1.5 monovalent amplifiers will offer some protection against EG.5, which is after all a branch of XBB. (Also known as XBB.1.9.2.5).
“Given that there are very few changes regarding the XBB.1.5 spike protein, which is the basis of the vaccines for fall 2023, I would expect the new vaccines to work well against it, and better than last year’s vaccines that they were based on ancestral vaccines and BA.5 Strains,” Doria-Rose said.
David C. Montefiori, PhD, who directs the HIV and COVID-19 Vaccine Research and Development Laboratory at Duke University Medical Center, echoed this in an email. “The fall vaccines are expected to continue to be highly effective against EG.5,” he said, adding that the F456L mutation “is not believed to have a major impact on the variant’s ability to escape the vaccine.”
Confirmation could come soon. Montefiori said her team and other researchers are analyzing serum samples from people who received the updated vaccine.
As of May of this year, only 17% of people in the US had received the original bivalent booster. For those who skipped a booster dose, del Río said at this point he recommends waiting a month or so until updated vaccines are available . His message: “COVID is not over. Get your reinforcements as soon as possible . ”
