Is Orthrus the Next Top-Dog COVID Variant?

The Omicron subvariant XBB.1.5 -- aka "Kraken" -- has climbed to more than 66% of new COVID-19 cases in the U.S., but a relatively new Omicron subvariant named after a two-headed dog may be nipping at its tentacles.

Over the last several weeks, CH.1.1 -- deemed "Orthrus" after a monster canine in Greek mythology -- accounted for less than 2% of new COVID cases in the U.S. as of January, per the CDC. However, Orthrus has a mutation, L452R, previously seen in the highly pathogenic Delta variant, and highly transmissible BA.4 and BA.5 variants, according to researchers from the Ohio State University in Columbus.

In a BioRxiv preprint, Shan-Lu Liu, MD, PhD, and colleagues said Orthrus emerged in Southeast Asia in November 2022, and now accounts for about a quarter of cases in the U.K. and New Zealand. At other times in the pandemic, the U.K. has served as a bellwether of what could hit the U.S. in terms of new variants and potential surges.

They also explained that Orthrus, along with another new variant, CA.3.1, possess a "consistently stronger neutralization resistance than XBB, XBB.1, and XBB.1.5, which is astonishing and warrants continuous monitoring and further investigations." Liu's group called for continuing current vaccination strategies, or the investigation of new ones, and the ongoing surveillance of emerging variants.

The February 2023 COVID epidemiological update from the World Health Organization (WHO) lists Orthrus among the top three most prevalent variants in Europe, clocking in at 12.3%, slightly behind BQ.1 at 13% and BQ.1.1 at 31.3%.

"WHO is currently prioritizing the tracking of four Omicron descendent lineages," the agency stated. "These variants are included on the basis of signals of an increase in prevalence or signs of growth rate advantage in some countries relative to other circulating variants, and additional amino acid changes that are known or suspected to confer fitness advantage."

During the second week of January, there were 3,473 (13.9%) sequences of BA.2.75, from which Orthrus is descended. That included BA.2.75.2 at 35 sequences (<1%), and then Orthrus, at 1,672 sequences (6.7%), according to WHO.

Recent CDC data show U.S. COVID cases, hospitalizations, and deaths trending down as of Feb. 1. Weekly cases were at 280,911, with daily average hospitalizations at 3,459, and weekly deaths at 3,452.

Liu and colleagues pointed out that "our study highlights the continued waning of 3-dose mRNA booster efficacy against newly emerging Omicron subvariants. This effect can be partially saved by administration of a bivalent booster, though escape by some subvariants, particularly CH.1.1 and CA.3.1, is still prominent."

Currently authorized bivalent COVID-19 boosters demonstrated similar protection against symptomatic illness from the XBB/XBB.1.5 Omicron subvariants as from BA.5-related subvariants, according to a recent CDC study.

Correction: This story has been updated to reflect that hospitalization data from the CDC represent a daily average.

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