COVID-19 FLiRT Variant

The COVID-19 FLiRT variant refers to a recently emerged group of sublineages of the Omicron strain of the SARS-CoV-2 virus. These subvariants have attracted scientific and public attention due to their increased transmissibility and potential to partially evade immunity acquired from vaccination or prior infection. The term FLiRT is derived from specific mutations found in the virus’s spike protein, represented by the letters F, L, R, and T, which play a vital role in the virus’s ability to infect human cells. While these variants do not appear to cause more severe disease, they signify the ongoing evolution of the virus and its ability to adapt in response to human immunity.

Background and Origin

Since the onset of the COVID-19 pandemic in 2019, the SARS-CoV-2 virus has undergone numerous mutations, leading to several variants and subvariants. Each major variant—such as Alpha, Delta, and Omicron—has demonstrated different levels of transmissibility and immune evasion. Among them, Omicron has produced the largest number of sub-lineages, evolving continuously as it spreads globally.
The FLiRT variants are sub-lineages of the JN.1 strain, itself a descendant of Omicron. They were first identified in late 2023 and began to spread more widely by early 2024. Their names—KP.2, KP.1.1, KP.3, and similar designations—refer to the technical lineage classifications used by virologists to track genetic differences among strains. However, to simplify communication, scientists coined the nickname “FLiRT” based on the characteristic amino acid mutations defining these variants.
These variants have become dominant in some countries, notably the United States, United Kingdom, and parts of Asia, where they have gradually replaced older Omicron subvariants such as XBB.1.5 and JN.1.

Meaning of “FLiRT” and Key Mutations

The name FLiRT refers to the key amino acid substitutions that occur in the virus’s spike protein:

• The change from Phenylalanine (F) to Leucine (L) at position 456 of the spike protein (denoted F456L).
• The change from Arginine (R) to Threonine (T) at position 346 of the spike protein (denoted R346T).

Together, these mutations—F→L and R→T—give rise to the acronym FLiRT.
The spike protein is the structure that allows the virus to attach to and enter human cells by binding to the ACE2 receptor. Mutations in this region can affect how tightly the virus binds to the receptor, how easily it enters cells, and how well it can evade the antibodies generated by previous infections or vaccines. The FLiRT mutations are believed to enhance the virus’s ability to spread efficiently and partially escape neutralising antibodies, contributing to their global rise in prevalence.

Transmission and Epidemiological Trends

By mid-2024, the FLiRT variants had become the predominant COVID-19 strains in several regions. For example, the KP.2 variant alone accounted for a significant proportion of sequenced COVID-19 cases in the United States and showed a similar trend in other countries.
Epidemiological studies suggest that the FLiRT variants possess a transmission advantage of roughly 10–20% over earlier Omicron subvariants. This increased transmissibility likely results from a combination of factors, including improved binding to human cells and partial immune evasion.
However, despite their rapid spread, available clinical data do not indicate that FLiRT variants cause more severe disease or higher hospitalisation rates compared with previous variants. Their spread instead reflects the virus’s natural evolution toward forms that can continue circulating in populations with existing immunity.

Clinical Presentation and Symptoms

The symptoms of infection with FLiRT variants are similar to those caused by other Omicron sub-lineages. Most patients experience mild to moderate respiratory illness, although severe cases can still occur, especially among vulnerable individuals such as the elderly or those with underlying health conditions.
Common symptoms include:

• Sore throat and nasal congestion.
• Cough, sometimes accompanied by chest discomfort.
• Headache and muscle pain.
• Fatigue and fever.
• Runny nose and sneezing.
• Occasional gastrointestinal symptoms such as nausea or diarrhoea.

Loss of taste or smell, which was prominent in early variants like Alpha and Delta, is less frequent with Omicron and its descendants, including FLiRT. Importantly, while many infections are mild or asymptomatic, people with compromised immune systems may still develop serious illness requiring medical care.

Vaccine Effectiveness and Immunity

The FLiRT variants have raised questions about the effectiveness of existing COVID-19 vaccines, particularly those based on earlier strains. Laboratory analyses indicate that these variants exhibit some degree of immune escape, meaning that antibodies generated by vaccines or prior infection may be less effective at preventing infection.
However, current evidence suggests that vaccines continue to provide strong protection against severe disease, hospitalisation, and death. This protection is due largely to the immune system’s broader response, which involves T-cells and memory B-cells that remain active even when antibody neutralisation is reduced.
Public health agencies recommend staying up to date with booster doses, especially as updated vaccines are developed to target the latest Omicron-derived variants. Boosters enhance the immune response and help maintain protection against evolving strains like FLiRT.

Global Health Response and Monitoring

Health authorities worldwide, including the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC), continue to monitor FLiRT variants closely through genomic surveillance programmes. This involves sequencing viral samples to track mutations and studying how these changes affect transmission, immunity, and disease severity.
Public health messaging emphasises that while the virus continues to evolve, the primary tools to mitigate COVID-19 remain unchanged:

• Vaccination and booster updates.
• Early testing and isolation when symptomatic.
• Wearing masks in high-risk or crowded environments.
• Maintaining good indoor ventilation and hand hygiene.

These measures collectively help limit transmission and protect vulnerable populations, especially during periods of increased viral activity.

Scientific Implications of FLiRT Variants

The emergence of FLiRT variants highlights the ongoing adaptive evolution of SARS-CoV-2. Viruses mutate constantly, but the scale of global transmission has accelerated the appearance of variants with specific survival advantages. In the case of FLiRT, these advantages lie in better adaptation to immune pressure within highly vaccinated and previously infected populations.
The persistence of mutations in similar regions of the spike protein across successive variants suggests evolutionary convergence, where the virus independently acquires similar mutations that improve its fitness. Such trends underline the need for continuous vaccine updates and broad-spectrum antiviral research.

Future Outlook

The FLiRT variants are expected to remain dominant or co-circulate with other Omicron offshoots for some time, depending on regional immunity levels and public health measures. As with previous waves, the virus may continue to evolve further, giving rise to new sub-lineages with additional mutations.
Scientists are already exploring next-generation vaccines that could target a wider range of variants or focus on more stable viral components, reducing the need for frequent updates. Pan-coronavirus vaccine research also aims to prepare for future coronavirus outbreaks by developing vaccines effective against multiple strains simultaneously.