New XEC Variant (KS.1.1 and KP.3.3 Recombinant): An Emerging Threat

Will the XEC Variant Be The Next Dominant COVID Strain? (Updated: 8/9/2024)

Aug 06, 2024

Updates:

The KS.1.1 and KP.3.3 recombinant variant is designated XEC
As of August 6th, there are 23 sequences in 7 countries
As of August 8th, there are 35 sequences in 9 countries
Estimated Growth Advantage: August 9, 2024: 97.82% (53.86% - 141.79%)

Introduction

The newly designated XEC variant is a KS.1.1 and KP.3.3 recombinant variant of SARS-CoV-2. It has been identified as a new lineage with a rapid and concerning spread across multiple countries. The early estimated growth advantage of this recombinant variant, as of August 9th is 97% (53% - 141%). In comparison, the current most prevalent variant, spreading faster than any other in the latest CDC variant proportions, has a growth advantage of 42% (40% - 42%). The margin of error is wider with XEC because it is so new but even on the low end, it beats KP.3.1.1. According to Mike Honey, it has a growth advantage of 4.6% per day. He said, on August 9th on X, “Globally, XEC is showing a robust growth advantage of 4.6% per day (32% per week) over JN.1.* + DeFLuQE variants. This is the fastest growth of any contender I am aware of. As the starting frequencies are quite low, any crossover looks like happening in September or later.”

This variant is worth identifying early because of its rapid spread, and the impact the mutations may have on the immune system. This variant combines genetic material from the KS.1.1 and KP.3.3 lineages, resulting in a unique set of mutations that may contribute to its enhanced transmissibility and potentially greater immune evasion.

U.S. Variant Proportions 7/21/2024 - 8/3/2024

Key Mutations

The recombinant variant is characterized by several notable mutations, including:

S:T22N, S:F59S ( S gene)

C18657T, C19716T (N gene)

C21627A, T21738C (ORF1ab)

T22928C, C23039G, G24872T, C25006T (S gene)

C28291A, G28884C (N gene)

Rapid Geographic Spread

As of August 6, 2024, there were 23 sequences detected in 7 countries, showing a remarkably fast geographic spread. By August 9th, it was 36 sequences in 11 countries on 3 continents.

graphic by Mike Honey posted on X. (click the pic for link)

The list below is missing some cases.

Germany: 11 cases

Netherlands: 4 cases (from 4 separate regions)

United States: 3 cases in Virginia - 5 total

Sweden: 3 cases

France: 1 case

South Korea: 1 case

Spain: 1 case

The earliest sequence was detected on June 24, 2024, in Berlin, Germany, with the latest reported on August 8, 2024, in the U.S., Netherlands, and Sweden. The rapid spread to multiple countries within such a short timeframe is concerning.

Potential Impact

The mutations in the Spike (S) protein may enhance the virus's ability to bind to ACE2 receptors, potentially increasing infectivity. Mutations in the Nucleocapsid (N) protein could affect viral replication and immune evasion. The rapid geographic spread suggests this variant may have a transmission advantage over other circulating strains.

Conclusion

The XEC (KS.1.1 and KP.3.3 recombinant) variant's swift international spread and unique mutation profile indicate it may possess increased transmissibility and potential immune escape capabilities. Continued genomic surveillance and further studies are crucial to understand its full impact on public health. Due to how new this variant is, we have limited information on how it may impact people but we will be watching this closely and updating on further developments.

Test Accuracy

A reminder for the FDA to check the efficacy of SARS-COV-2 tests which as we reported in the last update hasn't been followed up on by the FDA since 2023.

"Our study supports the previously published observations, highlighting the importance of simultaneous use of multiple targets in SARS‐CoV‐2 diagnostic assays and continuous monitoring of genetic variability of SARS‐CoV‐2 to ensure the specificity and sensitivity of commonly used diagnostic assays. Primers and probes should be aligned with an increasing number of reported SARS‐CoV‐2 variants to reassess their suitability for SARS‐CoV‐2 diagnostics." (3)

Refer a friend

Breakdown of Key Mutations in the KS.1.1 and KP.3.3 Recombinant Variant, XEC

N Gene Mutations

C18657T:

Location: ORF1b region

Effect: Non-structural protein (nsp14), which is involved in viral replication and transcription. (1)

C19716T:

Location: Nucleocapsid (N) gene

Effect: This mutation may impact the nucleocapsid protein, which is crucial for RNA binding and packaging of the viral genome. (1)

C28291A:

Location: Nucleocapsid (N) gene

Effect: This mutation could affect the stability and function of the N protein, potentially influencing viral replication and immune evasion.(1)

G28884C:

Location: Nucleocapsid (N) gene

Effect: Could alter the protein's interaction with host cell machinery, impacting viral assembly and release. (1)

ORF1ab Mutations

C21627A:

Location: ORF1ab region

Effect: Non-structural protein (nsp13), which has helicase activity essential for viral RNA synthesis.

T21738C:

Location: ORF1ab region

Effect: Non-structural protein (nsp13), potentially affecting its helicase function and impacting viral replication. (2)

Spike (S) Gene Mutations

T22928C: