The world is facing yet another twist in the ongoing battle against the COVID-19 pandemic, as a new variant of the virus, JN.1, has emerged as a separate variant of interest (VOI) from its parent lineage, BA.2.86.
The Emergence of JN.1
JN.1, a descendant lineage of BA.2.86, first appeared on the radar with the earliest sample collected on August 25, 2023. This variant is distinguished by an additional mutation in the spike protein, known as L455S.
As of December 16, 2023, a total of 7,344 JN.1 sequences have been submitted to GISAID from 41 different countries. This represents a significant portion, accounting for 27.1% of the globally available sequences during epidemiological week 48 (November 27 to December 3, 2023). Notable contributors to the JN.1 sequences include France (20.1%), the United States of America (14.2%), Singapore (12.4%), Canada (6.8%), the United Kingdom (5.6%), and Sweden (5.0%).
Public Health Implications
Despite the alarming increase in JN.1 cases, the World Health Organization (WHO) has, for now, categorized the additional public health risk posed by this variant as low at the global level. However, concerns linger, especially as countries in the northern hemisphere approach the winter season.
It is anticipated that JN.1 may contribute to a surge in SARS-CoV-2 cases, alongside other viral and bacterial infections, as winter approaches. Nevertheless, the current population immunity globally, as well as immunity generated by the XBB.1.5 booster vaccination, is expected to remain cross-reactive against JN.1, providing protection against symptomatic and severe disease. This, in turn, is likely to prevent a significant increase in the burden on national public health systems when compared to other Omicron sublineages.
However, it is crucial for countries entering the winter season to remain vigilant. The co-circulation of SARS-CoV-2 and other pathogens may exacerbate the respiratory disease burden, necessitating a comprehensive strategy to combat these challenges.
Immune Escape Potential
Despite this, protection provided by XBB.1.5 monovalent vaccines is expected to remain effective against JN.1. Nevertheless, WHO technical advisory groups, comprising scientists from around the world, are actively monitoring this situation.
Recommendations and Future Outlook
WHO, along with its Technical Advisory Group on SARS-CoV-2 Evolution (TAG-VE), recommends that member states take specific actions to address uncertainties related to antibody escape and severity of BA.2.86 and JN.1. These actions include conducting neutralization assays using human sera, representative of affected communities, and JN.1 live virus isolates, and performing a comparative evaluation to detect changes in indicators of severity.
In conclusion, the emergence of SARS-CoV-2 variant JN.1 has sparked concerns in the ongoing battle against the pandemic. While the current public health risk is assessed as low at the global level, the rapid increase in cases and the potential for immune escape warrant careful monitoring and decisive actions by health authorities worldwide. The battle against COVID-19 continues to evolve, with new challenges emerging, underscoring the importance of global cooperation and vigilance in the fight against the virus.
| Overall risk evaluation: Low | Based on its genetic features, JN.1 may possess some antigenic advantage evading previous immunity. With the limited data at this stage, the available evidence on JN.1 does not suggest additional public health risks relative to the other currently circulating Omicron descendent lineages. While there is a rapid increase in JN.1 infections, and likely increase in cases, available limited evidence does not suggest that the associated disease severity is higher as compared to other circulating variants. The risk evaluation will be updated as more evidence arises. | ||
| Indicator | Evidence | Level of risk | Level of confidence |
| Growth advantage | There are currently 7344 JN.1 sequences available from 41 countries, representing 27.1% of the globally available sequences in epidemiological week 48 (27 November to 3 December 2023). This is a rapid increase in the global proportion of JN.1 from 3.3% in epidemiological week 44 (30 October to 5 November 2023). Similarly for the same period and for countries with the highest proportion of JN.1 sequences, the prevalence of JN.1 in these countries rose from 10.9% to 45.5% for France, from 2.1% to 19.9% for the United States of America, from 1.4% to 72.7% for Singapore, from 1.0% to 9.9% for Canada, from 1.8% to 20.4% for the United Kingdom, and from 1.8% to 22.9% for Sweden. This rapid growth is observed across all the three WHO regions with consistent sharing of SARS-CoV-2 sequences, i.e. WPR, EUR and AMR, with the largest increase seen in WPR from 1.1% in epidemiological week 44 to 65.6% in epidemiological week 48. Wastewater data from multiple countries approaching the winter season points at a large wave of SARS-CoV-2 infections in the community (8), however that has not resulted yet into pressure on health care systems despite significant co-circulation of other viral and bacterial infections. BA.2.86.1 (JN.1’s parent lineage) replication kinetics on primary nasal epithelial cells (hNEC) have been observed to not be higher than other XBB- derived variants (2). However, it remains to be determined whether the high transmissibility of JN.1 in humans is also associated with enhanced fitness in primary hNECs and other cell types, and how much of that is linked to non-spike mutations. * see footnote for more explanations | High | High |
| Antibody escape | JN.1 in comparison with parent BA.2.86 lineage carries the additional spike mutation L455S that significantly enhances immune evasion capabilities (9). Variants such as HK.3 that carry the L455F mutation have been shown to possess increased transmissibility and immune escape ability compared to the parental EG.5.1 variant (10). Neutralization assay using rodent sera infected with BA.2.86 showed that NT50 against JN.1 was comparable to that against BA.2.86. However, the NT50 of XBB.1.5 and EG.5.1 breakthrough infection sera against JN.1 were significantly lower than that of HK.3 (2.6- to 3.1-fold) and BA.2.86 (3.8-fold) (3). In another study, whereas XBB.1, EG.5.1 and BA.2.86.1 neutralization were globally similar in individuals who experienced XBB breakthrough infections, JN.1 displayed higher immune evasion properties compared to BA.2.86.1 (2). JN.1 was 2.9-to-4.3-fold resistant to sera from individuals vaccinated with an XBB.1.5 mRNA vaccine booster (4). ** see footnote for more explanations | Moderate | Low |
| Severity and clinical/diagnostic considerations | A study from Belgium in ≥65-year-old patients has reported no difference in the odds of hospitalization with JN.1 compared to non-BA.2.86 variant (OR: 1.15 [0.74-1.78]) (11). On the contrary, preliminary data from Singapore indicated lower risk of hospitalization and severity in BA.2.86 elderly and younger cases (12). However, data are currently limited. *** see footnote for more explanations | Low | Low |
reference link : https://www.who.int/docs/default-source/coronaviruse/18122023_jn.1_ire_clean.pdf?sfvrsn=6103754a_3
- GISAID. Available from: https://gisaid.org/hcov19-variants/
- Planas D, Staropoli I, Michel V, Lemoine F, Donati F, Prot M et al. Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86 lineages combined increased fitness and antibody evasion. bioRxiv. November 2023. https://doi.org/10.1101/2023.11.20.567873
- Kaku Y, Okumura K, Padilla-Blanco M, Kosugi Y, Uriu K, Hinay Jr. AA et al. Virological characteristics of the SARS-CoV-2 JN.1 variant. bioRxiv. December 2023. https://doi.org/10.1101/2023.12.08.570782
- Wang Q, Guo Y, Bowen A, Mellis IA, Valdez R, Gherasim C, et al. XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants. bioRxiv. November 2023. https://doi.org/10.1101/2023.11.20.567873
- World Health Organization Technical Advisory Group on COVID-19 Vaccine Composition. Available from: https://www.who.int/news/item/13-12-2023-statement-on-the-antigen-composition-of-covid-19-vaccines
- World Health Organization Technical Advisory Group on COVID-19 Vaccine Composition. Available from:https://www.who.int/news/item/18-05-2023-statement-on-the-antigen-composition-of-covid-19-vaccines
- WHO. SARS-CoV-2 variant risk evaluation, 30 August 2023. Available from: https://apps.who.int/iris/rest/bitstreams/1528680/retrieve
- EU4S-DEEP – Wastewater observatory for public health – Digital European Exchange Platform. Available from: https://wastewater-observatory.jrc.ec.europa.eu/#/gis-area/3
- Yang S, Yu Y, Xu Y, Jian F, Song W, Yisimayi A, et al. Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure. bioRxiv. November 2023. doi: https://doi.org/10.1101/2023.11.13.566860
- Kosugi Y, Plianchaisuk A, Putri O, Uriu K Kaku Y, Hinay Jr. AA et al. Virological characteristics of the SARS-CoV-2 Omicron HK.3 variant harboring the “FLip” substitution. bioRxiv. November 2023. https://www.biorxiv.org/content/10.1101/2023.11.14.566985v1
- Statens Serum Institut, Denmark. Presentation at the WHO Technical Advisory Group (TAG-VE) meeting on 11 December 2023
- Ministry of Health, Singapore. Presentation at the WHO Technical Advisory Group (TAG-VE) meeting on 11 December 2023
