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

Stowe, Julia; Andrews, Nick; Kirsebom, Freja; Ramsay, Mary; Bernal, Jamie Lopez

doi:10.1038/s41467-022-33378-7

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

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

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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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Infections would be more affected by true waning of vaccine effectiveness than hospitalizations.
“and infections would be more affected by true waning of VE [37,41].”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [41]
A larger percentage of hospitalizations during the Omicron period likely had incidental, rather than causal, infections with SARS-CoV-2.
“Additionally, a larger percentage of hospitalizations during the Omicron period likely had incidental, rather than causal, infections with SARS-CoV-2”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [41]
Using hospitalization as an outcome for severe disease during Omicron would underestimate vaccine effectiveness against severe disease because vaccine effectiveness is lower against infection than against severe disease and hospitalizations may be unrelated to COVID-19.
“Since VE is lower against infection than against severe diseases (i.e. a decoupling of VE against infection and VE against severe disease) [15,17,18], VE against severe disease via hospitalization outcome would be underestimated.”
From COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study) (2024) · cites this paper as [17]
For vaccine effectiveness against progression from oxygen use to mechanical ventilation or death, additional adjustments were made for use of antivirals, monoclonal antibody therapy, steroids, anti-inflammatory drugs, anticoagulation, and proning; these potential confounders were determined a priori based on published reports.
“To estimate VE against progression from oxygen use to mechanical ventilation or death among COVID-19 patients, additional adjustments were made for use of antivirals, monoclonal antibody therapy, steroids, anti-inflammatory drugs (tocilizumab or baricitinib), anticoagulation, and proning. These potential confounders were determined a priori based on published reports [8,9,15,17].”
From COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study) (2024) · cites this paper as [17]
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Vaccine subtype and dose interval determine immunogenicity of primary series COVID-19 vaccines in older people
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Antibodies to S2 domain of SARS-CoV-2 spike protein in Moderna mRNA vaccinated subjects sustain antibody-dependent NK cell-mediated cell cytotoxicity against Omicron BA.1
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COVID-19 vaccine booster significantly decreases the risk of intensive care unit hospitalization in heart failure patients during the Omicron variant wave: A population-based study
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Effectiveness of the COVID-19 vaccines against severe disease with Omicron sub-lineages BA.4 and BA.5 in EnglandPreprint
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Effectiveness of vaccines in preventing hospitalization due to COVID-19: A multicenter hospital-based case-control study, Germany, June 2021 to January 2022
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An Overview of the Strategies to Boost SARS-CoV-2-Specific Immunity in People with Inborn Errors of Immunity
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Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population
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Who to Boost When: The Effect of Age and Dosing Interval on Delta and Omicron COVID-19 Incidence in the Open-label Phase of the COVE Trial
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Modelling the end of a Zero-COVID strategy using nirmatrelvir/ritonavir, vaccination and NPIs in Wallis and Futuna
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Protection of COVID-19 Vaccination Against Hospitalization During the Era of Omicron BA.4 and BA.5 Predominance: A Nationwide Case–Control Study Based on the French National Health Data System
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Effectiveness of mRNA-1273 bivalent (Original and Omicron BA.4/BA.5) COVID-19 vaccine in preventing hospitalizations for COVID-19, medically attended SARS-CoV-2 infections, and hospital death in the United StatesPreprint
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Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice
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Understanding the Omicron Variant in the COVID-19 Pandemic
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The elusive goal of COVID-19 vaccine immunity
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Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States
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CHALLENGES IN ESTIMATING THE EFFECTIVENESS OF 2 DOSES OF COVID-19 VACCINE BEYOND 6 MONTHS IN ENGLAND
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Protection against Omicron BA.1/BA.2 severe disease 0–7 months after BNT162b2 booster
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Effectiveness of BNT162b2 and CoronaVac COVID-19 Vaccination Against Asymptomatic and Symptomatic Infection of SARS-CoV-2 Omicron BA.2 in Hong KongPreprint
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Global Estimates of COVID‐19 Morbidity and Mortality: A Cohort Study and Mathematical Model Analysis
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Efficacy, Safety and Immunogenicity of Anti-SARS-CoV-2 Vaccines in Patients with Cirrhosis: A Narrative Review
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COVID-19 vaccines effectiveness against symptomatic disease and severe outcomes, 2021–2022: a test-negative case–control study
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Comparing Natural Language Processing and Structured Medical Data to Develop a Computable Phenotype for Patients Hospitalized Due to COVID-19: Retrospective Analysis
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Efficacy of Quinine Sulfate in Patients with Mild-To-Moderate COVID-19: A Randomized Controlled Trial
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COVID-19 Vaccine effectiveness against symptomatic infection and hospitalization in Belgium, July 2021-APRIL 2022Preprint
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Comparison of Omicron and Delta Variants of SARS-CoV-2: A Systematic Review of Current Evidence
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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: Stowe, Julia
Andrews, Nick
Kirsebom, Freja
Ramsay, Mary
Bernal, Jamie Lopez
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: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
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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Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study

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