COVID-19 Variant Update

15 July, 2024

COVID-19 Variants

As of July 15, 2024, the SARS-CoV-2 Omicron variants KP.2, KP.3 and LB.1 have high prevalence in the United States. CDC Nowcast projections estimate KP.3 to account for approximately 37% of new COVID-19 illnesses in the U.S. The proportion of illnesses caused by KP.3 rapidly increased from 9.4% estimated during the week of May 11 to 25% estimated during the week of June 11. As of July 15, the estimated percentage of illnesses caused by KP.2 is 24.4%, and the estimated percentage of illnesses caused by LB.1 is 14.9% (a decrease from the previous two-week period).

Pictured above is a figure showing recent emergence of JN.1, KP.2, KP.3, LB.1 and other Omicron strains in the U.S. For additional infographics depicting the change in variant proportions in the U.S. over time and/or geographically or phylogenetically, visit CDC’s COVID Data Tracker resource.

Variant nomenclature

Several emerging variants have been given specific names according to the mutations at key sites in the spike protein. So-called “FLip” variants possess mutations L for F at site 455, and F for L at site 456, in the backbone of XBB.1.5. An additional strain called “SLip" has also emerged, which has a JN.1 spike protein with an F for L at site 456 mutation; the “S” in “SLip" refers to the L for S at site 455 mutation characterizing JN.1. Finally, “FLiRT” variants are so named because they exhibit the mutations F for L at position 456, and R for T at position 346. The emerging strains KP.2, KP.3, and LB.1 are all considered to be in the family of “FLiRT” variants.

Immunity, Transmissibility and Vaccines: Last Updated July 15, 2024

Seroprevalence of SARS-CoV-2 and Omicron-specific antibodies

A very high proportion (>95%) of individuals currently have identifiable antibodies against SARS-CoV-2, either from infection or immunization or a combination of both. A recent large serosurvey aimed at investigating mucosal immunity in the Netherlands also identified very high (95%) spike-specific IgG in nasal samples of individuals.

Existing research in the U.S. indicates a large increase in SARS-CoV-2 antibody seroprevalence from the pre-Omicron to Omicron era across all age groups; it was estimated that by the third quarter of 2022, approximately two-thirds of individuals aged 16 years and older had been infected with SARS-CoV-2 with approximately half of individuals having hybrid immunity.

JN.1-specific immunity and transmissibility

The JN.1 variant is a subvariant of Omicron variant BA.2.86 and contains several mutations that are associated with escape from vaccine-mediated immune protection.  Emerging variants KP.2, KP.3 and LB.1 are descended from JN.1.

The JN.1 variant is antigenically distinct from the XBB.1.5 variant, which is the current target of monovalent COVID-19 vaccines. Recent research shows that JN.1 is very efficient at immune evasion (even more so than other Omicron variants), resulting in an increased reproductive number. Evidence from a small serological study has suggested that serological protection against SARS-CoV-2 is reduced against JN.1 variants compared to other BA.2.86 viruses among young adults who had received at least a complete primary series of SARS-CoV-2 vaccines. Additionally, a recent serological survey of 1,472 community-dwelling individuals found that although a majority of previously infected individuals had antibodies with neutralizing activity against JN.1, the neutralizing capacity was relatively low compared to neutralizing capacity against other SARS-CoV-2 strains. These findings are supported by an additional antigenic cartography analysis, which indicates that although XBB.1.5 booster sera was capable of neutralizing XBB sublineage variants (including JN.1), a five-fold titer difference was still observed.

Although JN.1 does appear to be more transmissible, it does not appear to cause more severe disease than other SARS-CoV-2 variants. 

KP.2- and KP.3-specific immunity and transmissibility

The KP.2 variant (also called JN. is a descendant of the JN.1 variant and contains several mutations that are associated with escape from vaccine-mediated immune protection. Preliminary research (not yet peer reviewed) suggests that the estimated relative effective reproduction number of KP.2 may be 1.22 times higher than the Re for JN.1. An additional rapidly emerging variant, KP.3, is believed to have similar virological and epidemiological characteristics to KP.2. A third emerging variant, LB.1, is also a "FLiRT" variant. Its rapid increase since early June 2024 indicates that it may overtake KP.3 as the dominant variant in the future.

Preliminary findings suggest higher viral fitness for KP.2 and KP.3 than prior JN.1 variants and subvariants, although a pseudovirus assay in this research suggested that the infectivity of KP.2 may be 10.5-fold lower than JN.1. Importantly, in virus neutralization assays, KP.2 showed substantial resistance to sera of individuals vaccinated with monovalent XBB.1.5 (i.e., the most recently updated COVID-19 vaccine). However, because of the high antigenic similarity between KP.2 and JN.1, it is expected that individuals with a recent JN.1 infection will likely have some cross-neutralizing antibody protection against KP.2.

KP.2 and KP.3 are members of a group of SARS-CoV-2 variants sometimes called FLiRT variants, and they are descended from the JN.1 Omicron variant. Other FLiRT variants, including KP.1.1, have also been identified as circulating in the U.S. but have not yet become as widespread as KP.2 or KP.3. (KP.1.1 is currently projected to account for approximately 9% of new COVID-19 illnesses in the U.S.)

LB.1-specific immunity and transmissibility

Like KP.2 and KP.3, LB.1 is a descendent of the JN.1 variant. Unlike KP.2 and KP.3, however, LB.1 exhibits an additional mutation (S:S31del) in addition to the substitutions present in KP.2 and KP.3 that designate them as FLiRT variants. Variants with this deletion such as LB.1 may sometimes be referred to as “deFLiRT,” indicating that the variant has the same mutations as other FLiRT variants with this additional deletion.

Preliminary results from a modeling study that has not yet been peer reviewed, from a research group at the University of Tokyo, indicate that the relative effective reproduction number (Reff) of LB.1 may be higher than KP.2 and KP.3. An additional subvariant that also exhibits the same mutation (S:S31del) as LB.1, called KP.2.3, also exhibited a higher relative Reff compared to KP.2 and KP.3 in the same study.

This study also conducted neutralization assays using breakthrough infection sera with XBB.1.5, EG.5, HK.3 and JN.1 infections as well as infection-naïve, monovalent XBB.1.5-vaccinated sera. In all four groups of sera, both LB.1 and KP.2.3 were found to have lower 50% neutralization titers compared to JN.1 and KP.2. Importantly, infection-naïve XBB.1.5-vaccinated sera had very low neutralization titers against JN.1 subvariants, and titer values were lower for KP.3, LB.1 and KP.2.3 compared to JN.1.

Taken together, these results suggest that the potential for infection with an emerging variant of Omicron is substantial even for individuals who have received the most recent COVID-19 vaccine updates. It appears that LB.1 and KP.2.3 exhibit higher infectivity and greater immune escape than KP.2 and KP.3. Due to the nature of the rapid emergence of LB.1, these results have not yet been corroborated by real-world epidemiological evidence.

Vaccines and current SARS-CoV-2 variants: Last updated July 15, 2024

Vaccination is still effective in preventing severe COVID-19, and vaccination with up-to-date SARS-CoV-2 vaccines does produce antibodies that can recognize JN.1 and its descendants.

Research has identified that JN.1 is resistant to monovalent XBB.1.5 vaccine sera, although data also suggest that JN.1 is unlikely to completely evade T-cell recognition. A recent report has identified substantially higher neutralizing antibodies elicited by bivalent (ancestral strain plus BA.4/BA.5) vaccines against several Omicron subvariants, including BA.2.86 and JN.1, compared to the original monovalent vaccine. There is very limited evidence to estimate neutralizing capacity of current vaccine-elicited antibody against KP.2 and KP.3 strains. However, preliminary evidence suggests that KP.2 and KP.3 (as well as other related FLiRT variants) may exhibit additional immune evasion capacity beyond JN.1; additionally, preliminary evidence (not yet peer reviewed) suggests that emerging variants LB.1 and KP.2.3 may exhibit additional immune evasion beyond what is exhibited by KP.2 and KP.3.

Preliminary estimates of vaccine effectiveness against disease likely caused by JN.1 are imprecise due to the recent emergence of JN.1 in the United States and the subsequent rapid rise of KP.2 taking its place. Although preliminary estimates suggest that there is still substantial VE against JN.1 (VE: 49%; 95% confidence interval: 19% – 68%), the VE estimate is lower than the estimate against non-JN.1 illnesses (VE: 60%; 95% confidence interval: 35% – 75%). These U.S.-based estimates for XBB.1.5 vaccine effectiveness against JN.1 were similar to preliminary estimates from a recent preprint using data from the Netherlands (41% VE in 18-to-59-year-olds and 50% in 60-to-85-year-olds). However, estimates for JN.1-specific vaccine effectiveness were lower in a large vaccine effectiveness study of Cleveland Clinic employees (19% VE). There is very limited evidence to estimate effectiveness of current vaccines against KP.2, KP.3, and LB.1. However, the effectiveness of current vaccines against these emerging variants is likely to be lower than against JN.1 given the additional immune escape properties exhibited by these variants that have been identified in recent research (not yet peer reviewed).

Due to these combined factors, the Advisory Committee on Immunization Practices recommended in late February 2024 that people 65 years of age and older should get an additional updated COVID-19 vaccine in spring 2024. Additionally, FDA’s Vaccines and Biological Products Advisory Committee and the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended in June 2024 that COVID-19 vaccines for fall/winter 2024-2025 should be monovalent vaccines with a JN.1-specific antigen.

Diagnostic Capacity for Variants: Last Ppdated July 15, 2024

Limited evidence available suggests that COVID-19 antigen and PCR tests are still capable of identifying recently emerged SARS-CoV-2 variants, such as XBB.1.5, EG.5.1, JN.1, KP.2, KP.3 and and FLiRT variants. Reduction or failure of the spike gene amplification in RT-PCR can be used as a (time-dependent) proxy indicator of JN.1 (versus other Omicron lineages) infection. 

Therapeutics: Last Updated July 15, 2024

Paxlovid continues to be effective against emerging SARS-CoV-2 variants, including JN.1 and FLiRT variants. Paxlovid is a protease inhibitor; its mechanism of action involves a part of the SARS-CoV-2 virus that is not related to the spike protein. It is therefore hoped that additional potential changes to the spike protein of SARS-CoV-2 variants will not affect the effectiveness of Paxlovid.

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