The story so far: The COVID-19 cycle spins again with new variants in circulation. KP.2 and KP1.1, dubbed ‘FLiRT’ variants, are descendants of the Omicron JN.1 which spread globally over the winter last year. The downstream variants are linked to new cases and a small surge in hospitalisation in the U.S., according to the Infectious Disease Society of America (IDSA). FLiRT cases have also soared in the U.K., South Korea and New Zealand, renewing fears of a fresh COVID-19 wave. The Indian SARS-CoV-2 Genomics Consortium (INSACOG) has detected 238 cases of KP.2 and 30 cases of KP1.1 circulating in India, as of May 6.
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The variants appear to outstrip their ancestor and other Omicron variants. KP.2, the more dominant strain of the two, in particular, is believed to leap past immunity built up from vaccines and previous infections. However, the periodic COVID-19 spikes are routine and to be expected as “COVID-19 will continue to morph into, not an endemic, but a cyclical disease”, says Rajeev Jayadevan, co-chairman of the National Indian Medical Association (IMA) Covid Task Force in Kerala. The distinction lies in endemic diseases, such as malaria, remaining steady in a region, while cyclical diseases like COVID-19 intermittently arrive in waves.
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The FLiRT variants reframe COVID-19 management as a longer affair, one that demands sustained surveillance, customising precautions and ensuring universal protection for the vulnerable.
What are the FLiRT variants?
KP.2 and KP1.1 sublineages are descendants of the JN.1 variant of the SARS-CoV-2 virus with two new added spike mutations. They are nicknamed the FLiRT group of variants (labelled so because of their technical names, F being replaced by L at position 456, and R supplanted by T at position 346). The acronym indicates two specific mutations, which when occur together, end up conferring greater invasive properties to the virus. Think of KP.2 (also called JN.1.11.1.2) as the ‘great-grandson’ of JN.1, which was classified as a Variant of Interest last December.
Between the two, KP.2 is reported to be more prevalent across countries. The US Centre for Disease Control and Protection (CDC) says it accounts for approximately 25% of new cases in the U.S. as of April 27; in the U.K., it contributed to about a quarter of total COVID-19 cases. The main variants circulating globally as of May 2024, arranged in the order of their prevalence, are KP.2, JN.1 and KP1.1.
“We can confirm that COVID-19 cases are rising in India, and KP.2 is a commonly found variant,” says Dr. Jayadevan. Per INSACOG, KP.2 has been detected predominantly in Maharashtra, Odisha, Goa and West Bengal; KP1.1 in West Bengal, Maharashtra and Gujarat; KP.3 in Uttarakhand. This is not to say that the variants are not circulating in other regions, but the proactive tracking in these states have identified JN.1’s descendants.
The symptoms of the new variant are similar to those of other Omicron subvariants: sore throat, cough, nausea, congestion, fatigue, headache, muscle or body ache, loss of taste or smell.
Are FLiRT varitants riskier than JN.1?
Researchers at the Kei Sato lab in Japan showed the KP.2 variant had an “increased immune resistance ability... more than previous variants including JN.1”. Their preliminary evidence showed that KP.2 was able to escape the immune protection derived not only from the most updated vaccine (the monovalent XBB.1.5 vaccine) but also from the breakthrough infection with JN.1 afterwards. KP.2 has “profound immune evasive properties”, notes Dr. Jayadevan. Even among people who got the JN.1 infection after the vaccination, their immune response could be surmounted by KP.2, the report showed.
“Most people who got COVID-19 in December 2023 had JN.1 infection, and you would think the JN.1 infection would protect them against its own descendants,” says Dr. Jayadevan, but that’s not the case with KP.2. The research, published on the pre-print server bioRxiv, showed the “reproduction number of KP.2 (Re) may be 1.22 times higher than the Re for JN.1”. The variant is thus able to leap over the most recently built immunity fence. More research is needed to understand how deeply and permanently the new mutations evade the immune system, researchers note. The immune-evading properties of KP.2 in some ways mimic JN.1’s tendency to challenge vaccine effectiveness. Even though JN.1 was found to be “very efficient at immune evasion (even more so than other Omicron variants)”, the IDSA cited data suggesting the variant is “unlikely to completely evade T-cell recognition”. Moreover, increased transmissibility does not necessarily mean the new variants will cause more severe COVID-19 illnesses.
In India, experts have also detected a new surge of cases since early April, with approximately one in six tests turning positive, compared to zero in March. With limited testing however, the exact prevalence and geographic spread is unknown. It is too early to say if all the new COVID-19 cases or hospitalisations are due to KP.2 or KP1.1 in India, explains Dr. Jayadevan.
Although immunisation with up-to-date SARS-CoV-2 vaccine produces antibodies recognising JN.1, experience from India and elsewhere indicates vaccination done earlier is still effective in preventing severe COVID-19 from newer variants. Health bodies such as IDSA have sounded the need for updating vaccines with more recent variants. The European Medicine Agency also recently recommended “updating COVID-19 vaccines to target the new variant JN.1” before another round of vaccinations is undertaken. Relatedly, AstraZeneca on May 7 said it had initiated the worldwide withdrawal of its COVID-19 vaccine due to a “surplus of available updated vaccines” since the pandemic. The withdrawal comes on the heels of scrutiny over Covishield’s rare side effects such as blood clots and low blood platelet counts.
Should India be concerned?
It is too early to know if JN.1’s descendants will trigger a new COVID-19 wave, as FLiRT variants flutter about. Precautions and prescriptions remain similar: maintain good hygiene, wear masks in crowded places, social distancing where necessary, stay home if unwell, and vaccinate.
“It’s not just death that you’re worried about, but also about the ill health that COVID brings with it.”Rajeev Jayadevan
At this time, there are numerous other ailments and public health challenges demanding attention and resources in India. Arriving in waves, the SARS-CoV-2 virus will continue to linger on the periphery; no longer causing profound illness on its own or being a leading cause of death. It can still pose a risk by destabilising people who are already on the border of ill health, Dr. Jayadevan says, like “the last straw that broke the camel’s back”. Moreover, the virus increases the burden of respiratory infections circulating during the summer, including common cold, allergies and rhinoviruses. Emerging research also flags the imperceptible but long-term health burden of Long COVID, including brain fog, confusion, and fatigue.
“COVID is not a thing of the past — it will continue to create waves”, remarks Dr. Jayadevan. Efforts will have to shift to learning how to ride the tide, instead of trying to tame it.
