This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log in
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 3;15(1):8550.
doi: 10.1038/s41467-024-52668-w.

Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage

Affiliations

Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage

Joseph A Lewnard et al. Nat Commun. .

Abstract

The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023-24. However, this surge in infections was not accompanied by COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86 lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86 lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86 lineages experienced greater numbers of documented prior SARS-CoV-2 infections. Cases infected with BA.2.86 lineages also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.

PubMed Disclaimer

Conflict of interest statement

J.A.L. has received research grants paid directly to his institution and consulting honoraria unrelated to this study from Pfizer. S.Y.T. has received research grants paid directly to her institution unrelated to this study from Pfizer. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Testing, S-gene targeted taction, and clinical outcomes during the study period.
Panels illustrate A the number of outpatient cases diagnosed daily from tests processed on Thermo Fisher TaqPath COVID-19 Combo Kit (TF) assays or non-TF assays; B the daily frequency of TF-tested specimens yielding positive results with S gene detected (non-BA.2.86 lineages) or S-gene target failure (BA.2.86-derived lineages); C the daily frequency of outpatient cases with positive SARS-CoV-2 testing results (organized by date of test) who experienced emergency department (ED) presentations within 14 days of testing, stratified according to presence or absence of acute respiratory infection (ARI) diagnoses associated with their ED presentation; D the daily frequency of outpatient cases with positive SARS-CoV-2 testing results (organized by date of test) who experienced hospital admission within 28 days of testing, stratified according to presence or absence of ARI diagnoses associated with their hospital admission; and E the daily frequency of outpatient cases with positive SARS-CoV-2 testing results (organized by date of test) who experienced intensive care unit (ICU) admission, initiation of mechanical ventilation, or death within 60 days of testing. Analyses include data from 46,067 eligible individuals throughout the study period, including 7,694 with TF-tested specimens. Source data to replicate the figure are provided as a Source Data file (fig1_source.xlsx).
Fig. 2
Fig. 2. Period-based comparison of prior vaccination, prior documented infection, and risk of progression to various clinical outcomes.
Panels illustrate A adjusted odds ratios, fitted via logistic regression models, for receipt of 5, 6, or ≥7 COVID-19 vaccine doses (relative to zero doses) among all outpatient cases diagnosed in the indicated periods relative to those diagnosed between 1 and 30 November, 2023; B adjusted odds ratios, fitted via logistic regression models, for documentation of 1, 2, or ≥3 prior SARS-CoV-2 infections (relative to zero documented prior SARS-CoV-2 infections) among all outpatient cases diagnosed in the indicated periods relative to those diagnosed between 1 and 30 November, 2023; and C adjusted hazard ratios, fitted via Cox proportional hazards models, for progression to emergency department (ED) presentation or hospital admission, due to any cause or in association with acute respiratory infection (ARI) diagnoses, comparing outpatient cases diagnosed in the indicated periods to those diagnosed between 1 and 30 November, 2023. All models adjust for age, sex, race/ethnicity, body mass index, history of cigarette smoking, prior-year healthcare utilization across all settings, Charlson comorbidity index, and median household income within cases’ census tract according to the categorization scheme indicated in Table 1. In addition, Cox proportional hazards models adjust for nirmatrelvir-ritonavir receipt as a time-varying exposure. Missing values were addressed via multiple imputation, with results pooled across five pseudo-dataset replicates. Tests for non-zero slopes in the Schoenfeld residuals of Cox proportional hazards models identified no violations of the proportional hazards assumption (two-sided p > 0.1 for all fitted models). Analyses include data from 46,067 eligible individuals throughout the study period. For all panels (a–c), points indicate maximum likelihood estimates, with surrounding lines delineating 95% confidence intervals; we generated estimates via Cox proportional hazards models (A, B) and conditional logistic regression models (c). Source data to replicate the figure are provided as a Source Data file (fig2_source.xlsx).
Fig. 3
Fig. 3. Observed and projected changes in risk of progression.
Panels illustrate A the daily proportion of outpatient tests exhibiting S-gene target failure (BA.2.86-derived lineages) among all tested within the primary analytic cohort; B estimates of the observed day-specific adjusted hazard ratio of emergency department (ED) presentation due to any cause (black), as well as projected estimates of the day-specific adjusted hazard ratio of ED presentation due to any cause resulting only from changes in lineage composition among outpatient-diagnosed cases (defined as aHR^t in the Methods; red); C for the outcome of hospital admission due to any cause, corresponding estimates of the observed day-specific hazard ratios and projected adjusted hazard ratios based only on changes in lineage composition (black and red, respectively); D for the outcome of ED presentations associated with acute respiratory infection (ARI) diagnoses, corresponding estimates of the observed day-specific hazard ratios and projected adjusted hazard ratios based only on changes in lineage composition (black and red, respectively); and E for the outcome of hospital admissions associated with acute respiratory infection (ARI) diagnoses, corresponding estimates of the observed day-specific hazard ratios and projected adjusted hazard ratios based only on changes in lineage composition (black and red, respectively). Analyses include data from 46,067 eligible individuals throughout the study period. For all panels (A–E), points indicate maximum likelihood estimates, with surrounding lines delineating 95% confidence intervals; we generated estimates via Cox proportional hazards models. Source data to replicate the figure are provided as a Source Data file (fig3_source.xlsx).
Fig. 4
Fig. 4. Sensitivity analyses addressing the association of BA.2.86 lineage detection with risk of emergency department presentation and hospital admission in the presence of differential misclassification of prior infection according to infecting lineage and clinical outcome.
We illustrate estimates of the adjusted hazard ratio of progression to A emergency department presentation and B hospital admission under analyses imputing "full" infection histories for cases under the assumption of differential misclassification of prior infection status. We consider multipliers of 1, 1.25, 1.5, 2, and 3 for the ratio of true to observed infections, first non-differentially among all cases (ω), and for the relative ratio of true to observed infections comparing cases who evaded the indicated outcome versus those who experienced it (ρ) and comparing cases infected with BA.2.86-derived lineages to those infected with non-BA.2.86 lineages (θ). Analyses include data from 46,067 eligible individuals throughout the study period. For all panels (A, B), points indicate maximum likelihood estimates, with surrounding lines delineating 95% confidence intervals; we generated estimates via Cox proportional hazards models. Gray bands illustrate 95% confidence intervals for estimates from the primary analysis (Table 3). Source data to replicate the figure are provided as a Source Data file (fig4_source.xlsx).

Update of

References

    1. US Centers for Disease Control and Prevention. Risk assessment summary for SARS CoV-2 sublineage BA.2.86. https://www.cdc.gov/ncird/whats-new/covid-19-variant.html (2024).
    1. US Centers for Disease Control and Prevention. CDC continues to track the growth of JN.1.https://www.cdc.gov/ncird/whats-new/JN.1-update-2023年12月22日.html (2024).
    1. Jeworowski, L. M. et al. Humoral immune escape by current SARS-CoV-2 variants BA.2.86 and JN.1, December 2023. Eurosurveillance29, 2300740 (2024). - PMC - PubMed
    1. Sheward, D. J. et al. Sensitivity of the SARS-CoV-2 BA.2.86 variant to prevailing neutralising antibody responses. Lancet Infect. Dis.23, e462–e463 (2023). - PubMed
    1. Yang, S. et al. Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure. Lancet Infect. Dis.24, e70–e72 (2024). - PubMed

Publication types

Substances

Supplementary concepts

Full text links
Nature Publishing Group full text link Nature Publishing Group Free PMC article
Cite

AltStyle によって変換されたページ (->オリジナル) /