Vaccine effectiveness against hospitalisation and comparative odds of hospital admission and severe outcomes with BQ.1, CH.1.1. and XBB.1.5 in England.

Background Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity. Methods A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant. Findings There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5 to 56.0%), 29.7% (95% C.I.; 7.5 to 46.6%) and 52.7% (95% C.I.; 24.6 to 70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5 to 9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77 to 0.99) and 0.88 (95% C.I.; 0.75 to 1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71 to 1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44 to 1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant. Interpretation Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1. Funding None.

[1]  J. L. Bernal,et al.  Risk of severe outcomes among Omicron sub-lineages BA.4.6, BA.2.75 and BQ.1 compared to BA.5 in England , 2023, medRxiv.

[2]  M. Ramsay,et al.  Duration of protection of ancestral-strain monovalent vaccines and effectiveness of bivalent BA.1 boosters against COVID-19 hospitalisation in England: a test-negative case-control study. , 2023, The Lancet. Infectious diseases.

[3]  D. Lye,et al.  Long-term real-world protection afforded by third mRNA doses against symptomatic SARS-COV-2 infections, COVID-19-related emergency attendances and hospitalizations amongst older Singaporeans during an Omicron XBB wave. , 2023, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  M. Chen,et al.  Severity of SARS-CoV-2 Omicron XBB subvariants in Singapore , 2023, medRxiv.

[5]  Z. Moore,et al.  Durability of Bivalent Boosters against Omicron Subvariants , 2023, The New England journal of medicine.

[6]  J. L. Bernal,et al.  Risk of severe outcomes among SARS-CoV-2 Omicron BA.4 and BA.5 cases compared to BA.2 cases in England , 2023, Journal of Infection.

[7]  Wenhui Li,et al.  Notes from the Field: Epidemiologic Characteristics of SARS-CoV-2 Recombinant Variant XBB.1.5 — New York City, November 1, 2022–January 4, 2023 , 2023, MMWR. Morbidity and mortality weekly report.

[8]  Z. Moore,et al.  Effectiveness of Bivalent Boosters against Severe Omicron Infection , 2023, The New England journal of medicine.

[9]  D. Douek,et al.  Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster , 2022, The New England journal of medicine.

[10]  S. E. Reese,et al.  Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults — VISION Network, Nine States, September–November 2022 , 2022, MMWR. Morbidity and mortality weekly report.

[11]  M. Exline,et al.  Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Hospitalization Among Immunocompetent Adults Aged ≥65 Years — IVY Network, 18 States, September 8–November 30, 2022 , 2022, MMWR. Morbidity and mortality weekly report.

[12]  Xuping Xie,et al.  Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster , 2022, Nature Medicine.

[13]  M. Kiso,et al.  Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB , 2022, The Lancet Infectious Diseases.

[14]  A. Gordon,et al.  Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants , 2022, Cell.

[15]  R. Sanjuán,et al.  Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies , 2022, bioRxiv.

[16]  J. L. Bernal,et al.  Effectiveness of the COVID-19 vaccines against hospitalisation with Omicron sub-lineages BA.4 and BA.5 in England , 2022, The Lancet Regional Health - Europe.

[17]  A. Presanis,et al.  Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England , 2022, Nature Communications.

[18]  J. L. Bernal,et al.  Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study , 2022, Nature Communications.

[19]  J. L. Bernal,et al.  COVID-19 vaccine effectiveness against the omicron (BA.2) variant in England , 2022, The Lancet Infectious Diseases.

[20]  S. Gharbia,et al.  Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant , 2022, The New England journal of medicine.

[21]  S. Bhatt,et al.  Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study , 2022, The Lancet.

[22]  Susan Hopkins,et al.  Healthcare-associated COVID-19 in England: A national data linkage study , 2021, Journal of Infection.

[23]  A. Hall The United Kingdom Joint Committee on Vaccination and Immunisation. , 2010, Vaccine.

[24]  S. Weich,et al.  The cohort study , 1998 .