COVID: The Global Spread of KP.2 What You Need to Know

The enduring presence of SARS-CoV-2, the virus responsible for the Covid-19 pandemic, is a reality we must acknowledge. Similar to the flu virus, SARS-CoV-2 continuously mutates to evade the immune responses triggered by vaccination or prior infection.

As we brace for the upcoming summer months, the emergence of new variants, like the recently identified KP.2, raises pertinent questions about the potential impact on public health.

Understanding the Threat

The primary concern lies in assessing the severity of each new variant of SARS-CoV-2.

While individuals who have been vaccinated or previously infected may have some level of protection against these variants, those who remain vulnerable face heightened risks. As we delve into the characteristics of KP.2 and its implications, it's essential to recognize its distinctiveness from previous strains.

The Rise of KP.2

KP.2, part of the FLiRT variant grouping, is gaining traction primarily in regions such as the United States, Canada, and the United Kingdom.

Despite limited sequencing efforts, the GISAID SARS-CoV-2 database has reported 1,816 cases of KP.2, hinting at its potential spread among populations.

Unpacking the FLiRT Variants

The FLiRT variants, including KP.2, share critical mutations in their spike proteins, notably the F456L and R346T mutations.

While structurally akin to previous major Omicron variants, such as BA.2.86 and JN.1, KP.2 exhibits distinctive features that warrant closer examination.

Spike Protein Variations

The spike protein mutations in KP.2, notably E484K and N501Y, are reminiscent of earlier variants of concern like the Alpha and Beta strains.

However, KP.2 distinguishes itself with unique alterations, particularly the R346T mutation, which could impact viral entry efficiency and antibody evasion.

Beyond the Spike Protein

Beyond spike protein variations, mutations in other genomic regions, such as the Orf1ab complex, structural proteins (E, M, and N), and accessory proteins (Orf3a-8), play pivotal roles in virus replication and pathogenicity.

Notably, the NSP3 T1465I mutation in KP.2 could influence various viral functions, further complicating the virus-host interaction.

Synonymous Mutations and Adaptation

Synonymous mutations, though not altering amino acid sequences, affect the virus's RNA structure and immune responses.

The abundance of synonymous mutations in KP.2 underscores its adaptive potential within the human host environment.

How do these mutations help the virus bind to cells while evading antibodies?

Two of these mutations—456 and 346—eliminate binding sites for antibodies that neutralize SARS-CoV-2. However, those same antibody binding sites are also important for the virus to bind to and enter cells.

So in evading antibodies, these FLiRT variants may have also lost some ability to bind to their receptor. At the same time, the 572 mutation appears to allow the virus to more tightly bind to cells and ultimately cause an infection.

Do people who recently had COVID have any protection against infection from FLiRT variants?

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.

Do we know yet how well the current COVID-19 vaccines work against the FLiRT variants?

Against JN.1, the vaccine designed around XBB.1.5 does generate some cross-reactive antibodies. Studies have not been yet 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. There is a question now of what the guidance will be going into the summer.

We’ve seen fairly low uptake of these additional boosters when they’re 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.

Should we anticipate these variants to drive a surge in cases this summer?

It’s certainly possible. The FLiRT variants would be high on my 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 cases of hospitalizations or deaths than we saw in the first couple years of the pandemic.

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.

Assessing the Risk

While KP.2's pathogenicity and transmissibility remain under scrutiny, its emergence underscores the need for vigilance, especially among unvaccinated or previously uninfected individuals.

As we navigate the summer months, the potential for a resurgence in Covid-19 cases looms large, with KP.2 serving as a harbinger of challenges ahead.

Conclusion

The saga of SARS-CoV-2 continues unabated, with new variants like KP.2 posing fresh challenges to global health efforts.

Understanding the intricacies of these variants and their implications is paramount in devising effective containment strategies. As we confront the uncertainties of the pandemic, staying informed and proactive remains our best defense against emerging threats.

Stay Informed, Stay Safe

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