COVID-19 FliRT Variant – A Coming Surge?

by Crispin Fernandez, MD

| Photo by Fusion Medical Association on Unsplash

In the first quarter of 2024, the KP.2 variant was causing about 4% of infections in the U.S., according to the CDC, while its parent strain, JN.1, was causing over 50% of infections concurrently. In early May, KP.2 comprised about 28% of infections, overtaking JN.1 as the dominant variant.

KP.2 is one of several variants being referred to as “FLiRT variants.” Prevailing variants dictate the formulation of COVID vaccines.

“FLiRT variants” is the term used to describe a whole family of different variants—including KP.2, JN.1.7, and any other variants starting with KP or JN—that have independently picked up the same mutations. It is called convergent evolution. They are all descendants of the JN.1 variant that has dominated the U.S. for several months.

The particular mutations that people call “FLiRT”s or “FLip”s refer to specific positions in the spike protein—in this case, positions 456, 346, and 572.

Viruses like SARS-CoV-2 frequently develop mutations. Mutating to evade antibody recognition often weakens their ability to bind to the cells they want to infect. We then see mutations appear that improve that binding ability. We have seen this cycle 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.

Two mutations—456 and 346—eliminate binding sites for antibodies that neutralize SARS-CoV-2. However, those same antibody binding sites are crucial for the virus to bind to and enter cells. So, these FLiRT variants may have also lost some ability to bind to their receptor in evading antibodies. At the same time, the 572 mutation appears to allow the virus to bind to cells more tightly and ultimately cause an infection.

A JN.1 infection should protect against all the FLiRT variants. The difference between JN.1 and these variants is only one or two amino acid changes, so antibodies can still bind to many other places. Infection from a variant older than JN.1 is less likely to offer as much protection.

The vaccine designed around XBB.1.5 does generate some cross-reactive antibodies against JN. 1. Studies have not yet been done with some of these newer variants, but those are likely to be a little less cross-reactive. It’s also been several months since many people received their last dose of the vaccine, and that immunity wanes over time.

Back in February, the CDC recommended an additional dose of the current COVID vaccine for adults 65 and older who received theirs in the fall. Now, there is a question of what guidance will be available in the summer. We’ve seen a relatively low uptake of these additional boosters when recommended, even in high-risk populations, so it’s unclear whether a third dose of the current vaccine will be recommended. If case numbers remain relatively low, it may not be necessary.

It’s certainly possible for these variants to drive a surge. The FLiRT variants would be high on the list of viruses that could cause another wave of infections in the U.S. That said, our definition of a wave has changed; while we still see case rates rise and fall throughout the year, we see much lower numbers of hospitalizations or deaths than we saw in the first couple of years of the pandemic.

“It is the time of year when governing bodies like the WHO and U.S. 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.”

And yet, while these waves are becoming smaller, they are still having the most significant 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 at the highest risk when new variants cause an uptick in cases.

It is the time of year when governing bodies like the WHO and U.S. 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 vaccine formulations. All of these FLiRT variants are within the JN.1 family of variants.

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 dominant so they can fine-tune the WHO recommendation to what they anticipate will be most prominent in the fall.

New COVID variants are likely to emerge after a decision is made. Still, the goal remains to select a formulation that, come fall, will match the circulating variants as closely as possible.

There is nothing new or different about these variants in terms of symptoms. We continue to see more mild disease, but that’s likely not because the virus is milder but because our immunity is so much stronger now. After years of vaccinations and infections, most of the population can better fight off an infection without as much concern for severe disease.

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. 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. At-home testing remains an essential tool for knowing whether you could infect others.

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 and antiviral drugs like molnupiravir and remdesivir. The companies that produce these drugs are constantly testing them against new variants to ensure they remain effective.

As with any respiratory virus, even when case rates nationally are low, it’s common to see infections increase in one area of the country but not another. Keep an eye on case rates in your region or anywhere you plan to travel to know whether you should take additional precautions, like wearing a mask or gathering in well-ventilated areas. Some local health departments report on virus levels in wastewater, which can signal an upcoming rise in cases. It is particularly helpful as people experience mild illness; those cases may not require hospitalization, but they’ll still be detected in wastewater data.

Keeping a few COVID tests around the house is always a good idea if you start feeling sick. Testing—whether at home or in a health care setting—will ensure you know what you’re infected with, which can inform the best treatment plan if you are in a high-risk group or your symptoms progress to more severe illness.

If you feel sick, follow the CDC’s simplified guidance for respiratory illnesses. It is especially important if you plan to spend time with friends or family who are at higher risk of severe illness.

ABOUT THE AUTHOR: Dr. Crispin Fernandez advocates for overseas Filipinos, public health, transformative political change, and patriotic economics. He is also a community organizer, leader, and freelance writer.

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