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Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome

Author

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  • Joseph A. Lewnard

    (University of California, Berkeley
    University of California, Berkeley
    University of California, Berkeley)

  • Vennis Hong

    (Kaiser Permanente Southern California)

  • Jeniffer S. Kim

    (Kaiser Permanente Southern California)

  • Sally F. Shaw

    (Kaiser Permanente Southern California)

  • Bruno Lewin

    (Kaiser Permanente Southern California)

  • Harpreet Takhar

    (Kaiser Permanente Southern California)

  • Sara Y. Tartof

    (Kaiser Permanente Southern California
    Kaiser Permanente Bernard J. Tyson School of Medicine)

Abstract

Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases in a large US healthcare system had at least 55% (95% confidence interval: 43–69%) higher adjusted odds of prior documented infection than time-matched BA.2 cases, as well as 15% (9–21%) and 38% (27–49%) higher adjusted odds of having received 3 and ≥4 COVID-19 vaccine doses, respectively. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals.

Suggested Citation

  • Joseph A. Lewnard & Vennis Hong & Jeniffer S. Kim & Sally F. Shaw & Bruno Lewin & Harpreet Takhar & Sara Y. Tartof, 2023. "Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37051-5
    DOI: 10.1038/s41467-023-37051-5
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    1. Joseph A. Lewnard & Parag Mahale & Debbie Malden & Vennis Hong & Bradley K. Ackerson & Bruno J. Lewin & Ruth Link-Gelles & Leora R. Feldstein & Marc Lipsitch & Sara Y. Tartof, 2024. "Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Joseph A. Lewnard & Vennis Hong & Jeniffer S. Kim & Sally F. Shaw & Bruno Lewin & Harpreet Takhar & Marc Lipsitch & Sara Y. Tartof, 2023. "Increased vaccine sensitivity of an emerging SARS-CoV-2 variant," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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