BA.2.86
BA.2.86 is a heavily-mutated Omicron subvariant of SARS-CoV-2, the virus that causes COVID-19. BA.2.86 is notable for having more than thirty mutations on its spike protein relative to BA.2. The subvariant, which was first detected in a sample from 24 July 2023, is of concern due to it having made an evolutionary jump on par with the evolutionary jump that the original Omicron variant had made relative to Wuhan-Hu-1, the reference strain first sequenced in Wuhan in December 2019. It is a mutation of BA.2, itself a very early mutation in the Omicron family. BA.2.86 was designated as a variant under monitoring by the World Health Organization on 17 August 2023, before being upgraded to a variant of interest on 19 December 2023. The variant was nicknamed Pirola by researchers, although no official sources use this name. Its foremost descendant, JN.1, became the dominant lineage in the Winter of 2023–2024, and has become the ancestor of nearly every circulating lineage since then.
Nomenclature
"BA.2.86" is a PANGO lineage ID number selected by scientists for the variant in question, based on its genetic lineage. Before the PANGO lineage number was selected for the BA.2.86 variant, some media outlets referred to it as "BA.6" while others referred to it as the "Pi Variant", around mid-August 2023. After the emergence of the Omicron variant in late 2021, the World Health Organization had stopped assigning new COVID variants Greek alphabet names, and in March 2023, they officially revised their policy to name only Variants of Concern – As no new COVID variants have been assigned the VOC status since the emergence of the parent Omicron lineage in Fall 2021, the WHO hasn't issued any new names since then. The lack of new names from the WHO and the reliance on only PANGO lineage numbers to track new COVID variants led to frustration among scientists and other groups, with some scientists criticizing the post-Omicron naming policy as a public communication failure and creating a false sense of security, and some in the media called the PANGO naming system "confusing" and even an "alphabet soup". In late 2022, following the proliferation of numerous Omicron subvariants, a group of scientists proposed a new naming system for significant COVID variants, although this idea failed to gain traction.Beginning in Fall 2022, infectious disease scientist T. Ryan Gregory decided to assign significant Omicron sublineages new names from Greek mythology, assigning the names "Typhon", "Cerberus", "Gryphon", "Kraken", and "Eris" to Omicron subvariants BQ.1, BQ.1.1, XBB, XBB.1.5, and EG.5, respectively. While these names caught on in the media, there were some groups that were displeased with his decision to name COVID variants. In late August 2023, T. Ryan Gregory coined the colloquial name "Pirola" to describe the BA.2.86 variant, by combining the names of the Greek letters pi and rho, which follow the letter omicron in the Greek alphabet; some news media outlets subsequently began using the nickname to refer to the variant. In the winter of 2023–24, T. Ryan Gregory assigned the nickname "Juno" to the JN.1 subvariant, which had become the dominant lineage. In June 2025, Gregory named the JN.1 subvariants NB.1.8.1 and XFG "Nimbus" and "Stratus", respectively, after cloud patterns.
History
The BA.2.86 variant was first detected around 24 July 2023, with Israel and then Denmark being the first to report detections. BA.2.86 possessed over 30 additional in its spike protein on top of BA.2's mutations, and 60 additional mutations compared to BA.2 overall, with a total of 90+ mutations compared to the original Wuhan wildtype. The largest proportion of initial samples came from South Africa, and with the closest related sequences being BA.2 samples in South Africa dating back to early 2022, researchers believed that BA.2.86 likely stealthily evolved within Southern Africa over the previous year, before emerging around May 2023. South Africa has been identified as the likely origin point of Omicron lineages BA.1, BA.2, BA.3, BA.4, BA.5, BA.2.86, and BA.2.87.1, with the Gauteng Province of South Africa playing a significant role in the emergence and/or amplification of those major Omicron lineages. The variant initially transmitted slowly, until it picked up the L455S mutation in its Receptor Binding Domain motif, as well as the NSP6:R252K and ORF7b:F19L mutations, giving rise to the JN.1 subvariant. This gave the virus enhanced transmissibility and immune evasion, and allowed its spread to begin taking off. In August 2023, France reported the first detection of the new JN.1 variant, and Luxembourg also reported an early detection of JN.1; the variant quickly gained a foothold in Europe. On 18 August 2023, when only six cases had been reported from four countries, the British healthcare authorities noted that its almost simultaneous appearance in several countries still operating detailed genomic surveillance indicated that it likely already was spreading more widely internationally, a view also shared by other experts. There has been an overall significant decrease in sequencing, reducing the possibility of tracking variants globally.By 30 August 2023, 24 cases of BA.2.86 had been detected in Canada, Denmark, Israel, Portugal, South Africa, Sweden, the United Kingdom and the United States. On 2 September, the variant was also detected in wastewater in a number of places where it was not yet confirmed directly in samples from people, including one U.S. state, Switzerland, Norway, Germany, Spain, Thailand and Hong Kong.
Hospitalization rates rose across the world as the winter approached, as JN.1 triggered another significant COVID wave, with the lineage exhibiting exponential growth in Europe and other regions. JN.1 drove the Winter 2023–2024 COVID wave, rapidly securing dominance within a few months and replacing XBB as the dominant COVID lineage, and eventually squeezing out the other previously-circulating Omicron lineages. Over the next 2 years, nearly all circulating SARS-CoV-2 viruses originated from the JN.1 lineage. The only exceptions were the hypermutated BA.3.2 variant, and a hypermutated BQ.1.1.1 descendant, which were variants that had emerged from dormant lineages last seen over 2–3 years ago, and each of which bore over 70 spike mutations compared to the Wuhan wildtype virus.
Biology
Mutations
The original Omicron Variant from late 2021 had over 53 mutations relative to the Wuhan-Hu-1 or B variant, which was far more than any previous SARS-CoV-2 variant. Thirty-two of these pertained to the spike protein, which most vaccines target to neutralize the virus, and 15 of those spike mutations were located in the Receptor Binding Domain, at residues 319–541. At the time of its discovery, many of the mutations were novel and not found in previous SARS-CoV-2 variants. The BA.2.86 variant uncovered two years later contained at least 35 additional spike protein mutations and 14 non-spike mutations on top of the base BA.2 lineage from early 2022, with a total of 90+ mutations compared to the original Wuhan wildtype virus. A large majority of BA.2.86's spike protein mutations were in the Receptor Binding Domain and the N-Terminal Domain.BA.2.86 saw the reappearance of the E484K and P681R spike mutations, which were present in the earlier Alpha Variant and Beta Variant, but had disappeared in the Omicron family for unknown reasons. In the N-Terminal Domain, the R21T, S50L, V127F, and R158G mutations were found to potentially improve viral entry efficiency, as well as enhancing immune escape from antibodies by adding N-glycosylation sites. In the Receptor-Binding Domain, the V445H, S450D, and L452W mutations were identified, which were rare up until the emergence of BA.2.86; these mutations were identified as potentially improving ACE2 binding or reducing antibody binding. BA.2.86 also bore six mutations in its Nsp3 protein : T24I, V238L, G489S, K1155R, N1708S, and A1892T, in addition to having a heavily-mutated Nucleocapsid protein. The ORF8 protein was also fully present in BA.2.86, while it was truncated in the XBB.1.5 variant that rose to dominance the previous winter. These changes were analyzed as likely working together to increase the virus's infectivity aggressively, escape from neutralizing antibodies, adapting to more efficient post-infection pathogenesis, and evasion from T cell recognition. BA.2.86 also readded the Δ69-70 deletions in its N-Terminal Domain, a feature that had been present in the BA.1, BA.4, and BA.5 Omicron lineages, but was absent in the XBB lineage. This deletion prevents one of the three common genomic segments used in SARS-CoV-2 diagnostic PCR tests from being detected, a phenomenon known as "S-Gene target failure", which had enabled easy tracking of the rapid rise of the Omicron BA.1 and then the BA.2 lineages. The primary JN.1 lineage acquired the S:L455S mutation in its spike protein, in addition to the NSP6:R252K and ORF7b:F19L mutations in non-spike regions. A 2025 study found that while the L455S spike mutation decreased ACE2 binding affinity in isolation, JN.1's other two key mutations, NSP6:R252K and ORF7b:F19L, offset this loss and increased the variant's replication efficiency above that of the ancestral BA.2.86. Based on these findings, the researchers concluded that non-spike mutations play a key role in Coronavirus evolution, and it was likely the non-spike mutations that were the biggest factor in JN.1 becoming dominant during the Winter of 2023–2024.
A 2025 study demonstrated that mutations in the Omicron B.1.1.529 strain significantly enhanced the release of two immunodominant HLA class I epitopes: 504-GHQPYRVVVL-513 and 496-SFRPTYGVGH-505. These epitopes are generated through the efficient processing—hydrolysis—of the receptor-binding domain by both constitutive proteasomes and immune proteasomes. These proteasomes facilitate protein cleavage into antigenic fragments, which are subsequently presented to the immune system to trigger a protective response. The authors emphasize the global significance of HLA haplotypes capable of presenting these epitopes. Key HLA molecules, such as HLA-B07:02, HLA-B08:01, HLA-B51:01, HLA-C01:02, HLA-C06:02, and HLA-C07:02, are widely distributed in the population, covering up to 82% and 27% of the global population for epitopes 504-GHQPYRVVVL-513 and 496-SFRPTYGVGH-505, respectively. This explains the decline in COVID-19 mortality rates in regions with a high prevalence of these haplotypes after December 2021, when Omicron became the dominant persistent strain. As an example, the study presents a comparative analysis of the situation in Bolivia and Paraguay. In Bolivia, where protective HLA haplotypes are more common, the COVID-19 mortality rate caused by Omicron was 1.5 times lower than in Paraguay, despite similar vaccination rates. This example vividly illustrates the importance of genetic predisposition in shaping resistance to the virus. Furthermore, the study addresses emerging Omicron lineages, such as BA.2.86 and JN.1. These strains retain key mutations in the 496-513 region, ensuring at least the release of epitope 504-GHQPYRVVVL-513, similar to B.1.1.529. Thus, the virus continues to evolve toward increased immunogenicity by acquiring new proteasomal cleavage sites due to mutations. The resulting peptides, presented on the cell surface, enhance viral recognition by the human immune system. These changes not only reduce disease severity but also promote the adaptation of the virus to the human population, facilitating its wider spread through asymptomatic carriers.