Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome
Open accessAbstract
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 had 15% (95% confidence interval: 9-21%) and 38% (27-49%) higher adjusted odds of having received 3 and ≥4 COVID-19 vaccine doses, respectively, than time-matched BA.2 cases, as well as 55% (43-69%) higher adjusted odds of prior documented infection. 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.
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Some studies have shown higher seroprevalence in the general population during the BA.4/5 period than during periods of BA.1/BA.2 predominance.
“Some studies have shown higher seroprevalence in the general population during the BA.4/5 period than during periods of BA.1/BA.2 predominance [39,40].”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [40]
The Results and Discussion compare documented prior infection among BA.4/BA.5 and BA.2 cases, not seroprevalence in the general population across periods of variant predominance. Searches for seroprevalence and population antibody comparisons found no passage addressing that claim; the available passages have no page numbers. (LLM, conf=0.76)
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BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
Cao, Y., Yisimayi, A., Jian, F., Song, W., Xiao, T., Wang, L., Du, S., Wang, J., Li, Q., Chen, X., et al. (2022) · Nature · doi:10.1038/s41586-022-04980-y · Cited by 1,288 · see citing works
Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa
Tegally, H., Moir, M., Everatt, J., Giovanetti, M., Scheepers, C., Wilkinson, E., Subramoney, K., Makatini, Z., Moyo, S., Amoako, D. G., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01911-2 · Cited by 707 · see citing works
Hansen, C. H., Friis, N. U., Bager, P., Stegger, M., Fonager, J., Fomsgaard, A., Gram, M. A., Christiansen, L. E., Ethelberg, S., Legarth, R. A., et al. (2022) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(22)00595-3 · Cited by 100 · see citing works
Lewnard, J. A., McLaughlin, J. M., Malden, D. E., Hong, V. X., Puzniak, L., Ackerson, B. K., Lewin, B. J., Kim, J. S., Shaw, S. F., Takhar, H. S., et al. (2022) · medRxiv · doi:10.1101/2022.10.02.22280623 · Cited by 24 · see citing works
Self-citationKirsebom, F. C. M., Andrews, N. J., Stowe, J., Ramsay, M. E., & Bernal, J. L. (2022) · medRxiv · doi:10.1101/2022.08.31.22279444 · Cited by 11 · see citing works
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Research works printed but not linked: 4
- Wolter, N. et al. Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages compared to BA.1 and Delta in South Africa. Nat Commun 13, 5860 (2022).
- Tseng, H. F. et al. Effectiveness of mRNA-1273 against infection and COVID-19 hospitalization with SARS-CoV-2 Omicron subvariants: BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. Preprint at doi:10.1101/2022.09.30.22280573 (2022). · DOI
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Feikin, D. R., Higdon, M. M., Andrews, N., Collie, S., Deloria Knoll, M., Kwong, J. C., Link-Gelles, R., Pilishvili, T., & Patel, M. K. (2023) · Vaccine · doi:10.1016/j.vaccine.2023.02.020 · Cited by 36 · see citing works
- Authors
- Lewnard, J. A., Hong, V., Kim, J. S., Shaw, S. F., Lewin, B., Takhar, H., & Tartof, S. Y.
- Affiliations
- University of California, Berkeley (US)
- Kaiser Permanente (US)
- Corresponding author
- Lewnard, Joseph A.
- Tartof, Sara Y.
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2022-08-02
- Volume
- 14
- Issue
- 1
- Pages
- 1407-1407
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10012300
- OpenAlex
- W4324303557
- Cited by
- 35
- References
- 6
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 13 · 2023: 12 · 2022: 5
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health and Human Services (75D3-121C11520)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01-AI14812701A1)
- National Institutes of Health (R01-AI14812701A1)
- Centers for Disease Control and Prevention (75D3-121C11520)
- National Institute of Allergy and Infectious Diseases (R01AI148127)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- SARS-CoV-2 Omicron subvariants, BA.4, BA.5, immune evasion, breakthrough infection, prior SARS-CoV-2 infection, COVID-19 vaccination, disease severity, hospitalization, intensive care unit admission, emergency department presentation, exposure misclassification, Delta variant
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Breakthrough Infections, Humans
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