FLiRT COVID Variants: What To Know

Over the last year, a whole different family of COVID-19 variants has emerged, sparking conversation on whether or not we’re flirting with dangerous territory again in the realm of COVID-19 evolution.

Collectively referred to as the FLiRT COVID variants, these subvariants are the latest in the long line of omicron variants we’ve seen over the past few years. But what makes these subvariants particularly unique is that they all carry the same set of brand-new mutations that allow the SARS-CoV-2 virus to infect its host and evade our immune system’s defenses.

Ahead of yet another COVID-19 peak season, pathologist Hannah Wang, MD, explains what we know so far about the FLiRT COVID variants and why they’re taking off.

What is the FLiRT variant?

All of the FLiRT COVID variants belong to the family of JN.1 variants that were dominant in the U.S. last winter. This includes KP.2 (which is what the COVID-19 vaccines are targeting this fall), KP.1.1, KP.2.3 and LB.1. The FLiRT variants get their name based on specific mutations that have occurred within specific amino acids of the SARS-CoV-2 spike proteins.

“This is the spike protein that is exposed on the surface of the virus that we generate immunity to and that we are vaccinated against,” explains Dr. Wang.

You can think of amino acids like molecular building blocks or Legos®. Each of them has a specific color, shape, size and chemical function. In total, 20 amino acids can be chained together in various configurations to create proteins.

The SARS-CoV-2 spike protein, for example, has 1,273 amino acids arranged in very specific positions for a unique configuration in its genetic code. Changing just one of those amino acids for another — the way you might switch out a grey chimney block for a red one reserved for the front of a building — has a widespread effect on how the virus looks and functions.

“If we change the building blocks of that protein, ostensibly, there could be potential immune evasion or varying levels of efficacy for protection of vaccination as well as prior infection,” she continues. “That’s why there’s all this concern.”

Each of the FLiRT variants carry these specific mutations in the genetic code of their spike proteins:

• At position 456, phenylalanine (F) has been replaced with leucine (L).
• At position 346, arginine (R) has been replaced with threonine (T).

By making these changes, the SARS-CoV-2 virus improves its ability to evade antibody recognition, while simultaneously weakening its ability to bind to cells. It’s like removing the garage door from a model home and replacing it with a brick wall — you can’t park the car in the garage without that pre-existing piece in place.

That makes the mutation at position 572, from threonine to isoleucine, that’s present in some FLiRT subvariants crucial: It makes up for those other weaknesses by allowing the virus to bind more tightly to cells.

“Scientists expect that the SARS-CoV-2 virus will continue to evolve,” says Dr. Wang. “As new variants emerge and the population builds up immunity to that variant, mutations that make the virus more successful at hiding from our immune system will be selected for, in short, survival of the fittest.”

KP.3 variants

KP.3 has often been thrown in with other FLiRT COVID variants. While KP.3 inherited the same mutations from previous FLiRT variants, it differs slightly because of an additional mutation. At position 493, glutamine (Q) has been replaced by glutamic acid (E), giving this variant the name FLuQE.

Research is ongoing to determine just how this mutation impacts the SARS-CoV-2 virus, but already, the FLuQE subvariants have become the dominant COVID-19 variants in the U.S. and other countries.

The U.S. Centers for Disease Control and Prevention (CDC) has determined that as of the beginning of October 2024, more than 57% of COVID-19 cases are related to KP.3.1.1. This direct descendent of KP.3 has inherited all the mutations from the previous FLuQE variant, but has an additional deletion of serine in position 31 (what some are calling a DeFLuQE variant).

As you can see, these changes will continue to happen as the SARS-CoV-2 virus continues to evolve, inspiring new forms of naming conventions and measures of tracking. And new subvariants will continue to emerge, in much the same way that the influenza (flu) virus evolves a little bit every year.

“Already, there’s a new emerging COVID-19 variant called XEC. It’s a recombinant variant, meaning two different JN.1 subvariants have combined,” shares Dr. Wang. “We’re seeing its incidence slowly creep up over the past few months.”

FLiRT symptoms

Because FLiRT variants like KP.2. and FLuQE variants like KP.3 are so closely related, the symptoms you experience are consistent with earlier forms of COVID-19. These symptoms include:

• Sore throat
• Body aches
• Cough
• Runny nose and congestion
• Fever or chills
• Shortness of breath

“If you experience any of these symptoms, it’s important to talk to your healthcare provider because you may be eligible for medication that can shorten the duration of your symptoms and prevent severe disease and hospitalization,” advises Dr. Wang.

In terms of the severity of your COVID-19 symptoms, it can vary. Some may feel severely unwell. Others may only have a mild infection. The severity of your symptoms largely depends on your experiences with previous COVID-19 infections, whether you’ve got the latest COVID-19 vaccine and how well your overall immune system can fight off infection.

If you’re immunocompromised, the most recent FLiRT and FLuQE variants may be increasingly dangerous for you to get.

“Part of different presentations in different patients can also be due to different immune statuses as well as coinfections,” she explains. “At the same time, as we saw this summer COVID wave, we were also seeing rhinovirus, and we’re seeing the highest levels of both Mycoplasma pneumoniae (walking pneumonia) and Bordetella pertussis (whooping cough) that we’ve seen since the start of the COVID-19 pandemic. This winter, we will almost certainly see influenza and respiratory syncytial virus (RSV) co-circulate with SARS-CoV-2.”

For now, COVID-19 guidelines and how long FLiRT and FLuQE variants are infectious remain the same as previous variants.

“We still have to wait for studies of these newer variants to understand how they slightly present in different ways compared to others,” she adds.

Does the COVID-19 vaccine protect against these new variants?

“The current dominant circulating variants are slightly different from the KP.2 variant that the vaccines are targeting, but they’re still in the same family,” clarifies Dr. Wang.

“We do expect that the vaccine will have some efficacy, we just don’t know exactly how much. Based on last year’s experience with how different the vaccine targets were from the dominant circulating subvariants, I do expect it’ll still provide a good amount of protection.”

U.S. public health authorities revisit the data every year to determine the effectiveness of new COVID-19 vaccines in an effort to keep up with the evolving SARS-CoV-2 virus. Just as we expect a new flu vaccine to target dominant influenza variants every year, we should expect a new vaccine targeting new COVID-19 variants every year around the same time.

“If you’re an older adult, if you’re immunosuppressed or you have family members at home who have those characteristics, those are the most important populations to consider getting vaccinated because even a little bit of protection will make a difference,” stresses Dr. Wang.