812 Variants
Armanda Kicks
At the end of March, the KP.2 variant was causing about 4% of infections in the U.S., according to the CDC, while its parental strain, JN.1, was causing over 50% of infections at that time. As of early May, KP.2 makes up about 28% of infections, overtaking JN.1 as the dominant variant.
In this Q&A, Andy Pekosz, PhD, a professor in Molecular Microbiology and Immunology, explains what virologists like him are seeing, whether these variants might cause a summer wave of infections, and how people can protect themselves.
Viruses like SARS-CoV-2 mutate frequently, and when they mutate to evade recognition by antibodies, this often weakens their ability to bind to the cells they want to infect. We then see mutations appear that improve that binding ability. This is a cycle we have seen many times with SARS-CoV-2. The fact that these different variants are picking up the same mutations tells virologists that this combination of mutations is helping the virus accomplish these goals most efficiently.
A JN.1 infection should provide pretty strong protection against all the FLiRT variants. The difference between JN.1 and these variants is only one or two amino acid changes, so there are still a lot of other places antibodies can bind to. Infection from a variant older than JN.1 is less likely to offer as much protection.
And yet, while these waves are becoming smaller, they are still having the greatest impact on our susceptible populations: the elderly, people who are immunocompromised and those with other secondary medical conditions. Everyone can play a role in protecting those populations that remain the highest-risk when new variants cause an uptick in cases.
This is the time of year when governing bodies like the WHO and FDA recommend a formulation for updated COVID vaccines that will roll out in early fall. Last year, the vaccines were based on the XBB.1.5 variant, and only a few months later, the JN.1 variant became the dominant variant in the U.S.
At the end of April, the WHO announced that their COVID vaccine advisory group advises using the JN.1 lineage as the antigen for the upcoming formulations of the vaccine. All of these FLiRT variants are within the JN.1 family of variants.
Here in the U.S., the FDA has postponed its meeting to determine the fall 2024 COVID vaccine from mid-May to early June. That gives them more time to see which of the FLiRT variants is becoming the dominant one so they can fine-tune the WHO recommendation to what they anticipate will be most prominent in the fall.
The period of infectiousness for these FLiRT variants remains the same as with JN.1 and previous omicron variants: After exposure, it may take five or more days before you develop symptoms, though symptoms may appear sooner. You are contagious one to two days before you experience symptoms and a few days after symptoms subside. And as with previous variants, some people may have detectable live virus for up to a week after their symptoms begin, and some may experience rebound symptoms.
Yes, the good news is that Paxlovid is still recommended for high risk individuals. It still works against variants up to JN.1, and based on the sequencing of the FLiRT variants, they should still be susceptible to Paxlovid, as well as to antiviral drugs like molnupiravir and remdesivir. The companies that produce these drugs are always testing them against new variants to ensure they continue to be effective.
Variant classification serves as an important communication tool for alerting EU/EEA countries about the emergence of SARS-CoV-2 variants with concerning properties likely to impact the epidemiological situation in the EU/EEA.
The ECDC Strategic Analysis of Variants in Europe (SAVE) Working Group is a multidisciplinary team comprising of ECDC Experts working in Respiratory Viruses, Microbiology, Bioinformatics, Mathematical Modelling, Epidemic Intelligence, Emergency Preparedness and Response and Vaccine-Preventable Diseases and Immunisation. Currently meetings are held once per month to assess the observed or predicted impact of currently circulating and newly emerging SARS-CoV-2 variants in the EU/EEA and globally.
ECDC utilises three categories of variant classification to communicate increasing levels of concern about a new or emerging SARS-CoV-2 variant: variant under monitoring (VUM), variant of interest (VOI) and variant of concern (VOC). Classification criteria and recommended Member state actions are available here:
Variant surveillance data, including the distribution of VOC and VOI variant proportions in the EU/EEA and detailed country-specific COVID-19 epidemiological updates are available as part of the European Respiratory Virus Surveillance Summary (ERVISS).
Following classification of a VOC or VOI, multiple closely related sub-lineages may emerge. To facilitate reporting of variant detections by countries to TESSy, a table listing sub-lineages assigned to VOCs and VOIs as of 23 July 2024 is available here.
As of 3 March 2023, ECDC has de-escalated BA.2, BA.4 and BA.5 from its list of SARS-CoV-2 variants of concern (VOC), as these parental lineages are no longer circulating. ECDC will continue to categorise and report on specific SARS-CoV-2 sub-lineages in circulation that are relevant to the epidemiological situation.
These additional variants of SARS-CoV-2 have been de-escalated based on at least one the following criteria: (1) the variant is no longer circulating, (2) the variant has been circulating for a long time without any impact on the overall epidemiological situation, (3) scientific evidence demonstrates that the variant is not associated with any concerning properties.
(c) The property of concern for this variant was the fact that there are reports of difficulties associated with detecting it in upper respiratory tract samples. These difficulties were not caused by primer-template mismatch but rather by the virus not being present in sufficient quantities in the upper respiratory tract.
The tables are based on genomic, phenotypic, and epidemiological evidence available on a global scale, but focus on the potential impact for the European region. For this reason, the list may deviate slightly from the global variants of concern and interest list and labels produced by WHO and published in the WHO weekly epidemiological update.
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).
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.
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.
The KP.2 variant (also called JN.1.11.1.2) 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.