But COVID surveillance, testing, and reporting of data has slowed tremendously over the past 3 years. Today, 90% of the world's nations no longer reliably report COVID hospitalizations or deaths, making it very difficult to track changes in the evolution and behavior of new variants.
As the most recent CDC COVID `NOWCAST' (Jun 20th) (see above) warns:
This shows weighted and nowcast estimates for the United States. The table and map show estimates for the 2-week period ending on 6/21/2025 (nowcast) if available.
Due to low numbers of sequences being reported to CDC, precision in the most recent reporting period is low. CDC is moving to longer reporting periods to gather the number of sequences required to provide reliable nowcast estimates.
As a result, the most recent estimates from the CDC on the prevalence of the top 3 COVID variants in the United States (see below) comes with a huge amount of uncertainty.
The XFG variant; the subject of today's blog, could account for as little as 3% or as high as 41% of recent cases. This reduction in testing and sequencing of samples, sadly isn't just an American problem.
While we continue to see compelling evidence that COVID infections increase the risks of developing `long COVID', and other sequelae (see BMC Neurology: Long-term Neurological and Cognitive Impact of COVID-19: A Systematic Review and Meta-analysis in over 4 Million Patients), governments around the globe have opted to minimize the threat, in order to `move on' from the pandemic.
This morning we have a new risk assessment on the XFG variant from the WHO's TAG-VE (Technical Advisory Group on SARS-CoV-2 Virus Evolution), which currently - and based on limited information - puts the risk from this emerging subvariant as `Low'.The fact remains that COVID continues to evolve a furious rate - both in humans and in non-human species - and many more COVID variants are expected to continue to come off the evolutionary assembly line going forward.
Executive Summary
XFG has been designated a SARS-CoV-2 variant under monitoring (VUM) with increasing proportions globally. Considering the available evidence, the additional public health risk posed by XFG is evaluated as low at the global level. Currently approved COVID-19 vaccines are expected to remain effective to this variant against symptomatic and severe disease.
Several countries in the South-East Asia Region have reported a simultaneous rise in new cases and hospitalisations, where XFG has been widely detected. Current data do not indicate that this variant leads to more severe illness or deaths than other variants in circulation.Initial Risk Evaluation of XFG, 25 June 2025
XFG is a SARS-CoV-2 variant that is a recombinant of the lineages LF.7 and LP.8.1.2, with the earliest sample collected on 27 January 2025. XFG is one of seven VUMs tracked by the WHO and was designated as a VUM on 25 June 2025 [1,2]. In comparing JN1 with XFG and NB.1.8.1, the currently dominant SARS-CoV-2 variant, distinct mutational profiles in the Spike protein can be identified; however, some amino acid changes are held in common:
NB.1.8.1 = JN.1 + [T22N, F59S, G184S, A435S, F456L, T478I, Q493E] - [T478K]
XFG = JN.1 + [T22N, S31P, K182R, R190S, R346T, K444R, V445R, F456L, N487D, Q493E, T572I] -[V445H]
Spike mutations at amino acids 478 and 487 have been shown to enhance the evasion of Class 1/2 antibodies [3]. Using pseudoviruses and plasma from BA.5 breakthrough infections with JN.1 or XDV+F456L infection, XFG showed 1.9-fold reduction in neutralization compared to LP.8.1.1 [3]. In mice previously immunized with SARS-CoV-2 variant vaccines, further immunisation using monovalent KP.2 or monovalent LP.8.1 mRNA vaccines elicited similar or modestly lower neutralising antibody titres against XFG than those elicited by
immunising KP.2 or LP.8.1 antigens [3,4].
As of 22 June 2025, there were 1648 XFG sequences submitted to GISAID [5] from 38 countries, representing 22.7% of the globally available sequences in epidemiological week (EW) 22 of 2025 (26 May to 1 June 2025).
This is a significant rise in proportion from 7.4% four weeks prior in EW19 of 2025 (5 to 11 May 2025), Table 1. Between EW 19 and EW 22 of 2025, XFG increased in proportion in all the three WHO regions that are consistently sharing SARS-CoV-2 sequences, i.e. an increase from 1.6% to 6.0% for the Western Pacific region (WPR), from 7.8% to 26.5% for the Region of the Americas (AMR), and from 10.6% to 16.7% for the European Region (EUR).Albeit with fewer sequence submissions, XFG proportion increased from 17.3% to 68.7% in the South-East Asia Region (SEAR), where NB.1.8.1 had rapidly gained dominance earlier in the Spring. In India, XFG has been the dominant variant throughout the Spring and NB.1.8.1 remained very rare. There are only 2 XFG sequences from the African Region (AFR), and 65 from the East Mediterranean Region (EMR).
(SNIP)
* Growth advantage
Level of risk: Moderate, as XFG is growing substantially across all WHO regions with consistent SARS-CoV-2 sequence data sharing.
Confidence: Low, as XFG expansion has only begun recently, there are low levels of sequencing data, and
NB.1.8.1 is still growing in proportion in AMR and EUR.
** Antibody escape
Level of risk: Low, as the immune evasion of XFG in available data is of a similar magnitude to prior JN.1 sublineages upon their emergence. Additionally, XFG clusters with other JN.1 sublineages within antigenic cartography data based on sera from immunised mice.
Confidence: Low, as XFG antigenicity has only been assessed in a single study using pseudoviruses with serological data from two cohorts. Additional laboratory studies using sera from different cohorts and regions are needed to further assess the risk of antibody escape.
*** Severity and clinical considerations
Level of risk: Low, as currently there are no reports of elevated disease severity associated with this variant. Available evidence doesn't suggest resistance to Remdesivir and Nirmaltevir.
Confidence: Low. Currently there are no studies assessing the impact of this variant on clinical outcomes.
Although, there is regular co-ordination and data sharing between all WHO Regional Offices, countries reporting of data on severe outcomes such as new hospitalizations, ICU admissions and deaths with the WHO has been decreased substantially.
Therefore, caution should be taken when interpreting trends in routine surveillance of severe cases for increased severity. No studies have been conducted yet on the potential impact of the variant on the activity of antivirals like Remdesivir and Nirmaltevir.
Admittedly, I've no reason to suspect that this XFG variant will be any worse than any of the last dozen or so COVID variants to go on a world tour.
That said, immunity - whether from vaccines or past infections - wanes over time. And far fewer people are getting COVID (and Flu) shots these days, with most people believing the risks of severe illness to be low.
Ultimately, the systematic global dismantling of our surveillance and reporting systems (see No News Is . . . Now Commonplace) leaves us wide open to be sucker punched when some new, or antigenically unique, pathogen inevitably does emerge.
At which point we'll have to go from covering our eyes, to covering our mouths and noses again.
