The SARS-CoV-2 variant BA.2.86, nicknamed “Pirola,” emerged in the summer of 2023 as a highly divergent lineage of the Omicron family. First detected in Denmark in July 2023, its unique genetic profile quickly drew global attention from public health agencies and researchers. This variant represented a significant evolutionary leap, appearing when most circulating strains were descendants of the XBB lineage. Its sudden appearance prompted immediate efforts to assess its potential impact on transmission, immunity, and disease severity.
Genomic Signature and Origin
The BA.2.86 variant is classified as a sub-lineage of the Omicron BA.2 variant, which was dominant in 2022. BA.2.86 was distinguished by an unusually large accumulation of mutations, particularly within the spike protein. The spike protein harbors over 30 mutations compared to its BA.2 predecessor and the co-circulating XBB.1.5 variant.
This dramatic genetic change in a single jump is comparable in magnitude to the shift seen when the original Omicron variant emerged. Such a significant evolutionary leap suggests that BA.2.86 did not evolve through gradual community transmission. A leading hypothesis for its origin involves a prolonged infection in an immunocompromised individual, allowing the virus time to accumulate numerous mutations under selective pressure.
Another plausible theory suggests the variant may have evolved in a non-human animal host before spilling back into the human population. The sporadic detection of early BA.2.86 cases in geographically distant locations also complicated efforts to pinpoint a single origin of human community spread. Regardless of the exact source, the large number of alterations to the spike protein signaled a major change in the virus’s behavior, especially concerning its interaction with the human immune system.
Immune Response and Current Protection
The extensive mutations on the BA.2.86 spike protein immediately raised concerns about its ability to evade immunity from prior infections and existing vaccines. Laboratory studies were initiated to determine how effectively antibodies generated by previous exposure could neutralize the new variant. Early findings indicated that BA.2.86 was antigenically distinct from previous strains, yet it was not universally more resistant to the collective antibody response than the dominant XBB sub-lineages.
Despite fears of immune escape, data suggested that BA.2.86 showed similar or even less neutralization evasion compared to some co-circulating XBB variants. The current generation of updated vaccines, which target the XBB.1.5 sub-lineage, were effective at generating cross-reactive antibodies against BA.2.86. This monovalent XBB.1.5 booster significantly enhanced the neutralization capacity of human sera against the BA.2.86 pseudovirus in laboratory settings.
Real-world evidence supported these findings. Vaccine effectiveness of the XBB.1.5 vaccine against symptomatic infection was estimated to be around 41% to 50% in different adult age groups. This protective effect, while not preventing all infections, is consistent with the primary goal of current vaccination strategies: maintaining robust protection against severe disease, hospitalization, and death. The variant did demonstrate a unique antigenic profile, notably showing resistance to certain monoclonal antibody treatments that were still effective against other Omicron strains.
Clinical Presentation and Severity
Initial reports on BA.2.86 infections indicated that the clinical presentation was broadly similar to other Omicron variants, often manifesting as typical upper respiratory symptoms. Early cases were not associated with unusually severe illness, which was reassuring given the variant’s significant genomic divergence. However, an outbreak in a UK care facility highlighted the variant’s capacity for high transmissibility in vulnerable, close-contact settings.
Laboratory investigations offered a mixed perspective on the virus’s intrinsic severity. Some studies found BA.2.86 possessed an increased ability to infect human lung epithelial cells compared to previous Omicron variants, raising theoretical concerns about potential for more severe disease. Conversely, virological research using animal models, such as hamsters, suggested that BA.2.86 had an attenuated pathogenicity compared to the ancestral BA.2 variant.
The most significant impact came from the rapid emergence of BA.2.86’s descendant, JN.1, which acquired a mutation that enhanced its fitness. The JN.1 sub-lineage rapidly became the dominant circulating strain globally, associated with a modest increase in COVID-19 activity, infections, and hospitalizations during the subsequent winter season. While BA.2.86 itself did not lead to a disproportionate spike in severe outcomes, the overall context of its lineage suggests its mutations did allow for greater spread and a sustained public health challenge.
Tracking and Global Monitoring
The emergence of BA.2.86 underscored the necessity of robust global surveillance systems to detect and track highly mutated SARS-CoV-2 strains. The variant was designated a Variant Under Monitoring (VUM) by the World Health Organization (WHO) shortly after its initial detection in August 2023. It was later reclassified as a Variant of Interest (VOI) due to its increasing prevalence and unique genetic characteristics.
Public health agencies employed a multicomponent surveillance approach to monitor its spread. This strategy included traditional genomic sequencing of clinical samples and innovative methods like wastewater surveillance. Wastewater monitoring proved valuable for detecting BA.2.86 in communities, often signaling its presence days or weeks before clinical cases were officially reported.
For instance, the variant was identified through wastewater analysis in locations like New York City and Ohio before a corresponding clinical case was confirmed. This early warning system remains a crucial tool, especially as the frequency of clinical testing and subsequent genomic sequencing has declined since the height of the pandemic. The data gathered from these diverse tracking methods provides scientists with the situational awareness necessary to assess the public health risk of new variants and inform vaccine updates.