Editorial: COVID-19 Six Years on and Endemic Omicron Variants of SARS-CoV-2 Under Monitoring Now Include NB.1.8.1 (Nimbus) and XFG (Stratus)

Six years ago, in December 2019, patients in Hubei Province, China, reported symptoms of atypical pneumonia, unresponsive to treatment, and in Wuhan, an outbreak of similar cases was reported to the World Health Organization (WHO) [1]. By January 30, 2020, the WHO declared that COVID-19 was a public health emergency of international concern (PHEIC) [2]. The SARS-CoV-2 virus was identified as the cause of COVID-19 within months, but by March 2020, there were more than 118,000 reported cases in 143 countries and 4,291 reported deaths, prompting the WHO to declare a COVID-19 pandemic [3]. On May 5, 2023, the Director-General of the WHO announced the end of the pandemic and advised that COVID-19 was now an endemic or established and ongoing health issue and no longer a PHEIC [2]. The declining mortality rates, hospital admissions, and intensive care unit (ICU) admissions, and increasing population immunity to SARS-CoV-2 due to the success of vaccine programs led to the end of the pandemic [2].

Table 1 summarizes some key timelines and events in the history of SARS-CoV-2 and the COVID-19 pandemic from December 2019 to November 2025. Currently, in 2025, international public health experts and organizations, including the WHO and the UK Health Security Agency (UKHSA), have raised significant concerns about complacency in COVID-19 infection surveillance, monitoring, and control [4]. Since the end of the COVID-19 pandemic, there has been a global decline in testing and reporting of SARS-CoV-2 infections, leading to incomplete and inaccurate data on virus incidence, infection trends, and the emergence of viral variants, including new Omicron variants [4]. In 2018, in their annual Research and Development Blueprint, the WHO identified 10 pathogens (Pathogen X) with the potential to cause health emergencies from Disease X due to lack of treatment or vaccines, among them was severe acute respiratory syndrome (SARS) coronavirus [5]. Seven years on from this first WHO prediction, SARS-CoV-2 variants must now be increasingly considered contenders for not-too-distant future pandemics, which could be caused not by Disease X but by COVID-19.

On May 31, 2021, the Virus Evolution Working Group of the WHO recommended the revised naming of SARS-CoV-2 variants of concern (VOC) and variants of interest (VOI) [6]. By November 26, 2021, the WHO included the Omicron variant (B.1.1.529) of SARS-CoV-2 on the list of variants of concern (VOC), which became the dominant variant in many countries [7]. On January 21, 2022, the WHO published its recommendations for priority actions in response to the Omicron variant (B.1.1.529) of SARS-CoV-2 [7]. During 2022, the Omicron variant (and its five lineages, BA.1, BA.2, BA.3, BA.4, and BA.5) became the predominant cause of COVID-19 worldwide [7]. On June 7, 2022, the WHO added a new category to its SARS-CoV-2 variant tracking system, the VOC Lineages Under Monitoring (VOC-LUM), to inform global health authorities of the VOC lineages and sublineages that may require priority attention and monitoring [8]. On January 12, 2023, the Omicron XBB.1.5 (Kraken) subvariant (a sublineage of the XBB variant) accounted for 49.1% of COVID-19 cases in the US [9]. On August 8, 2023, the WHO identified EG.5 (Eris) as a variant under monitoring (VUM) and a variant of interest (VOI) [10]. Two years ago, by December 18, 2023, mutations in the SARS-CoV-2 spike protein occurred rapidly, with the Omicron variant (B.1.1.529) and its subvariants, Kraken (XBB.1.5), Eris (EG.5), and Pirola (BA.2.86) successively dominant in the previous two years [11,12]. Also, the WHO designated JN.1 as a separate variant of interest (VOI) from the parent lineage, BA.2.86, due to its rapid spread [11].

Towards the end of 2025, genomic analysis of the infecting SARS-CoV-2 virus identified the most common circulating variants to be XFG (Stratus), which is dominant in Europe and the Americas, and NB.1.8.1 (Nimbus), which is dominant in the Western Pacific region [4]. By November 2, 2025, the total number of COVID-19 cases reported to the WHO since 2020 stood at 778,900,250 [13]. From mid-2025, there has been a weekly increase in reported COVID-19 cases, particularly in North America and Europe [13]. However, because infection surveillance has not been maintained at the levels seen during the COVID-19 pandemic and surveillance relies mainly on hospital admissions data, infection rates are likely to be much higher [4].

On June 25, 2025, the WHO Technical Advisory Group on Virus Evolution (TAG-VE) reported a risk evaluation for two SARS-CoV-2 variants under monitoring (VUM), NB.1.8.1 (Nimbus) and XFG (Stratus) [14,15]. The NB.1.8.1 (Nimbus) variant of SARS-CoV-2 is derived from the recombinant variant XDV.1.5.1 and harbors spike mutations that enhance binding affinity to angiotensin-converting enzyme 2 (ACE2), potentially increasing transmissibility [14]. The WHO evaluated the global risk from NB.1.8.1 (Nimbus) as low and that the currently approved COVID-19 vaccines were expected to remain effective against this Omicron variant of SARS-CoV-2 for symptomatic and severe COVID-19 [14]. The NB.1.8.1 (Nimbus) variant is designated as a variant under monitoring (VUM), with prevalence increasing as the variant LP.8.1 declines [14].

The XFG (Stratus) variant of SARS-CoV-2 is a recombinant of the lineages LF.7 and LP.8.1.2 and is now one of seven variants under monitoring (VUM) tracked by the WHO [15]. The WHO evaluated the global risk from XFG (Stratus) as low and that the currently approved COVID-19 vaccines would remain effective against this Omicron variant of SARS-CoV-2 for symptomatic and severe COVID-19 [15]. Several countries in Southeast Asia have reported a simultaneous rise in new cases and hospitalizations where XFG (Stratus) is prevalent [15]. However, infection with the XFG (Stratus) variant does not result in more severe illness than other circulating SARS-CoV-2 variants [15].

Recently, Guo and colleagues showed that although XFG (Stratus) exhibits immune evasion, it has a relatively low binding affinity for ACE2 [16]. However, NB.1.8.1 (Nimbus) shows a balanced profile of ACE2 binding and immune evasion, supporting its potential for future prevalence [16]. In November 2024, an Omicron variant, BA.3.2, was detected in South Africa, which has been shown to have more than 50 mutations compared to its ancestral BA.3 lineage, and to exhibit antibody evasion but with low ACE2 binding capability and infectivity [16]. However, BA.3.2 has the potential to become a dominant Omicron variant during the coming year [16].

The rapid rate of SARS-CoV-2 spike mutations that result in new viral variants, which can be associated with increased infectivity and disease severity, highlights the need for continued surveillance and the possibility of future epidemics and pandemics of COVID-19 [12]. Therefore, the beginning of the era of endemic COVID-19, associated with new Omicron variants of SARS-CoV-2, presents new challenges that remain to be addressed to prevent future pandemics [2].

Conclusions

As 2025 ends, and six years on from the initial reports of SARS-CoV-2 cases that led to the COVID-19 pandemic, complacency in infection control and surveillance has resulted in a concerning increase in infection from endemic Omicron variants, including NB.1.8.1 (Nimbus) and XFG (Stratus).