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

Joseph A. Lewnard (), Parag Mahale, Debbie Malden, Vennis Hong, Bradley K. Ackerson, Bruno J. Lewin, Ruth Link-Gelles, Leora R. Feldstein, Marc Lipsitch and Sara Y. Tartof
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Joseph A. Lewnard: University of California, Berkeley
Parag Mahale: Kaiser Permanente Southern California
Debbie Malden: Kaiser Permanente Southern California
Vennis Hong: Kaiser Permanente Southern California
Bradley K. Ackerson: Kaiser Permanente Southern California
Bruno J. Lewin: Kaiser Permanente Southern California
Ruth Link-Gelles: US Centers for Disease Control & Prevention
Leora R. Feldstein: Centers for Disease Control and Prevention
Marc Lipsitch: Centers for Disease Control and Prevention
Sara Y. Tartof: Kaiser Permanente Southern California

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52668-w

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