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Cited by 166SARS-CoV-2 and COVID-19 ResearchCOVID-19 epidemiological studiesCOVID-19 Clinical Research Studies

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Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study

Open access
Stowe, Julia, Andrews, Nick, Kirsebom, Freja, Ramsay, Mary, Bernal, Jamie Lopez·2022·Nature Communications
DOI 10.1038/s41467-022-33378-7PMC PMC9523190

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Abstract

The Omicron variant has been associated with reduced vaccine effectiveness (VE) against mild disease with rapid waning. Meanwhile Omicron has also been associated with milder disease. Protection against severe disease has been substantially higher than protection against infection with previous variants. We used a test-negative case-control design to estimate VE against hospitalisation with the Omicron and Delta variants using PCR testing linked to hospital records. We investigated the impact of increasing the specificity and severity of hospitalisation definitions on VE. Among 18–64-year-olds using cases admitted via emergency care, VE after a 3rd dose peaked at 82.4% and dropped to 53.6% by 15+ weeks after the 3rd dose; using all admissions for > = 2 days stay with a respiratory code in the primary diagnostic field VE ranged from 90.9% to 67.4%; further restricting to those on oxygen/ventilated/intensive care VE ranged from 97.1% to 75.9%. Among 65+ year olds the equivalent VE estimates were 92.4% to 76.9%; 91.3% to 85.3% and 95.8% to 86.8%. Here we show that with milder Omicron disease contamination of hospitalisations with incidental cases is likely to reduce VE estimates. VE estimates increase, and waning is reduced, when specific hospitalisation definitions are used.

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Fig. 1 Vaccine effectiveness estimates with 95% confidence intervals 7+ days after a 3rd dose against symptomatic disease and different hospitalisation outcomes by age group and variant. ECDS Emergency Care Dataset—administrative data from emergency departments, SUS Secondary Users Service—administrative data from all secondary care which is coded on discharge, ECDS All all admissions through emergency care. ECDS Resp Coded respiratory SNOMED coded admission through emergency care, SUS All admitted with a respiratory ICD code, SUS Not Primary admitted with a respiratory ICD code not in the primary diagnosis field, SUS Primary admitted with a respiratory ICD code in the primary diagnosis field. 0 days, 1+ days, 2+ days, 3+ days: length of stay, for example, 1+ means at least one overnight stay. Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously testing positive.
Fig. 1 Vaccine effectiveness estimates with 95% confidence intervals 7+ days after a 3rd dose against symptomatic disease and different hospitalisation outcomes by age group and variant. ECDS Emergency Care Dataset—administrative data from emergency departments, SUS Secondary Users Service—administrative data from all secondary care which is coded on discharge, ECDS All all admissions through emergency care. ECDS Resp Coded respiratory SNOMED coded admission through emergency care, SUS All admitted with a respiratory ICD code, SUS Not Primary admitted with a respiratory ICD code not in the primary diagnosis field, SUS Primary admitted with a respiratory ICD code in the primary diagnosis field. 0 days, 1+ days, 2+ days, 3+ days: length of stay, for example, 1+ means at least one overnight stay. Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously testing positive.CC BY · PubMed Central
Fig. 2 Vaccine effectiveness estimates with 95% confidence intervals against hospitalisations using ECDS by age group and manufacturer (all symptomatic controls, Omicron only). a 18–64: Two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, b 18–64: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, c 65 and older: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, d 65 and older: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of the test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously tested positive.
Fig. 2 Vaccine effectiveness estimates with 95% confidence intervals against hospitalisations using ECDS by age group and manufacturer (all symptomatic controls, Omicron only). a 18–64: Two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, b 18–64: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, c 65 and older: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, d 65 and older: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of the test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously tested positive.CC BY · PubMed Central
Fig. 3 Vaccine effectiveness estimates with 95% confidence intervals against hospitalisations >=2 days and >=2 days and on oxygen/ventilated/on ICU using SUS by age group and manufacturer (all symptomatic controls, Omicron only). Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of the test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously tested positive. a 18–64: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, b 18–64: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, c 65 and older: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, d 65 and older: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose.
Fig. 3 Vaccine effectiveness estimates with 95% confidence intervals against hospitalisations >=2 days and >=2 days and on oxygen/ventilated/on ICU using SUS by age group and manufacturer (all symptomatic controls, Omicron only). Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of the test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously tested positive. a 18–64: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, b 18–64: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, c 65 and older: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, d 65 and older: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose.CC BY · PubMed Central

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Research works printed but not linked: 3

  1. World Health Organization. COVID-19 Weekly Epidemiological Update, Edition 82 (World Health Organization, 2022).
  2. Wilhelm, A. et al. Limited neutralisation of the SARS-CoV-2 Omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies. EBioMedicine. 82, 104158 (2022). · DOI · Paper page
  3. Andrews, N. et al. Duration of protection against mild and severe disease by Covid-19 vaccines. New Engl. J. Med. 386, 340–350 (2022). · DOI · Paper page

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Metadata

Authors
Stowe, J., Andrews, N., Kirsebom, F., Ramsay, M., & Bernal, J. L.
Affiliations
  • UK Health Security Agency (GB)
  • London School of Hygiene & Tropical Medicine (GB)
  • National Institute for Health and Care Research (GB)
Corresponding author
Stowe, Julia
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-09-30
Volume
13
Issue
1
Pages
5736-5736
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-33378-7
PMC
PMC9523190
OpenAlex
W4298145582
Cited by
166
References
24
Citations by year
2026: 7 · 2025: 19 · 2024: 43 · 2023: 67 · 2022: 30
FWCI
19.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
COVID-19 vaccines, vaccine effectiveness, Omicron variant, Delta variant, hospitalization, waning vaccine effectiveness, test-negative case-control design, third dose, older adults, emergency department admission
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, Hospitalization, Humans, Oxygen, Vaccination, Case-Control Studies

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