Medical News: In the ongoing evolution of SARS-CoV-2, a newly designated sub-lineage known as RF.5 has captured the attention of genomic surveillance experts. First detected in late 2025, this variant has shown remarkably swift growth in prevalence, most notably in Singapore, where it has approaching dominance.
SARS-CoV-2 latest variant: RF.5 is catching the attention of many researchers and variant hunters globally
As of early February 2026, RF.5 stands out from currently circulating major strains such as BA.3.2, XFG, and NB.1.8.1, prompting increased monitoring amid limited global sequencing data. This
Medical News report examines the available genomic and epidemiological details on RF.5, drawing from recent lineage proposals and surveillance observations. While information remains preliminary due to the variant's recent emergence and sparse sampling, its trajectory highlights the continued challenges posed by the virus's adaptability.
Lineage and Evolutionary Background
RF.5 descends directly from the PY.1.1.1 lineage, which evolved through a series of Omicron-derived sub-lineages. Its path includes JF.1.16.1 (built on JN.1 with additions such as S:R346T and F456L), LF.7 (incorporating S:T22N, S31P, K182R, R190S, K444R, and Orf9b:I5T), LF.7.9 (adding S:L441R, H445P, and A475V), and PY.1.1.1 (with S:K679R, A435S, and Orf3a:G44E).
RF.5 represents a further divergence, classified as an evolved FLiRT-like variant within the broader Omicron family, reflecting ongoing selective pressures that drive genetic changes favoring transmission or immune escape.
Key Mutations
RF.5 is primarily defined by mutations in the spike protein, which plays a critical role in host cell entry. The core defining mutation is S:K478T, present in all known sequences, while a subset also carries S:M153I. These changes occur atop the inherited mutations from parent lineages, particularly affecting the receptor-binding domain, potentially influencing ACE2 receptor affinity or antibody recognition.
Although detailed functional studies are not yet available, patterns in related Omicron descendants suggest such alterations could enhance viral fitness. Note that convergent mutations like S:A435S appear in other lineages (e.g., XFJ.3.1.2) but are not part of RF.5's signature.
Prevalence and Geographic Spread
Globally, 17 sequences carry the defining S:K478T mutation across seven locations, with 12 of these also featuring S:M153I across five locations. This limited sampling likely underestimates true circulation, as the variant appears to have emerged in regions with reduced sequencing intensity.
In Singapore, RF.5 was first identified in the second half of December 2025 (with the earliest known sequence dated September 26, 2025), followed by what variant hunters term as explosive growth.
Prevalence rose from negligible levels in early December to approximately 8.6% in the second half of that month
, reaching 25.0% in the first half of January 2026 and climbing further to 36.7% in the second half.
Recent updates indicate around 25-30% in the latest Singapore samples, with logistic growth models suggesting continued increases.
Outside Singapore, sequences have been reported in the United States (California), England (linked to travelers from India and Saudi Arabia), Spain, France, and Russia, indicating early international spread facilitated by travel.
Growth Advantage and Immune Evasion
The variant's ascent in Singapore—from near absence to over one-third of sequences in roughly one month—implies a selective growth advantage over co-circulating strains. However, local factors such as potential superspreader clusters or sampling biases cannot be excluded at this stage, and precise relative growth rate calculations are not yet available.
Global sequencing volumes, now at roughly 1% of peak pandemic levels, constrain broader assessments.
Regarding immune evasion, no specific experimental data exist for RF.5's performance against vaccines, prior infections, or monoclonal antibodies. Its spike protein mutations, particularly in the receptor-binding domain, raise theoretical concerns about partial escape from existing immunity, consistent with trends in other Omicron sub-lineages.
Due to its divergence from dominant variants, RF.5 has been flagged for priority monitoring by surveillance networks.
Public Health Implications
The swift emergence of RF.5 in Singapore underscores SARS-CoV-2's persistent capacity for rapid evolution and regional dominance. While no indications point to increased disease severity, heightened transmissibility could elevate case numbers and pressure healthcare systems if the variant expands further, such as into neighboring countries like Thailand.
Public health responses should prioritize genomic surveillance through wastewater monitoring and clinical sequencing, and heightened vigilance at international travel hubs.
As formal lineage reviews continue and additional sequences accumulate, clearer insights into RF.5's global trajectory and properties are expected soon.
References:
https://github.com/sars-cov-2-variants/lineage-proposals/issues/3043
https://x.com/xz_keg/status/2018367110435799325
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