Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines
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Abstract
BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. RESULTS: Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults. CONCLUSIONS: We observed limited waning in vaccine effectiveness against Covid-19-related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.
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Additional vaccine effectiveness studies revealed waning of vaccine-induced protection over time.
“However, as vaccination campaigns progressed, additional vaccine effectiveness (VE) studies revealed waning of the vaccine-induced protection over time [8-13]”
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 [9]
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Experimental — accuracy not yet measuredModest reductions in vaccine effectiveness against infection and mild disease have been observed with the beta and delta variants, although effectiveness against severe disease has remained high for at least 6 months after primary immunization with two Covid-19 vaccine doses.
“Modest reductions in vaccine effectiveness against infection and mild disease have been observed with the beta (B.1.351) and delta variants, although effectiveness against severe disease has remained high for at least 6 months after primary immunization with two Covid-19 vaccine doses.”
From Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern (2021) · cites this paper as [18]
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“However, as vaccination campaigns progressed, additional vaccine effectiveness (VE) studies revealed waning of the vaccine-induced protection over time [8-13], more so against symptomatic infection than against severe COVID-19 disease [14].”
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- Authors
- Andrews, N., Tessier, E., Stowe, J., Gower, C., Kirsebom, F., Simmons, R., Gallagher, E., Thelwall, S., Groves, N., Dabrera, G., Myers, R., Campbell, C. N. J., Amirthalingam, G., Edmunds, M., Zambon, M., Brown, K., Hopkins, S., Chand, M., Ladhani, S. N., Ramsay, M., & Lopez Bernal, J.
- Affiliations
- University of Oxford (GB)
- From the United Kingdom Health Security Agency (N.A., E.T., J.S., C.G., F.K., R.S., E.G., S.T., N.G., G.D., R.M., C.N.J.C., G.A., M.E., M.Z., K.B., S.H., M.C., S.N.L., M.R., J.L.B.), the National Institute of Health Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation, London School of Hygiene and Tropical Medicine (N.A., C.N.J.C., G.A., K.B., M.R., J.L.B.), the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London (M.Z., J.L.B.), Guy’s and St. Thomas’ Hospital NHS Trust (M.C.), and the Paediatric Infectious Diseases Research Group, St. George’s University of London (S.N.L.), London, and Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford (S.H.) — all in the United Kingdom.
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2022-01-27
- Volume
- 386
- Issue
- 4
- Pages
- 340-350
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC8781262
- OpenAlex
- W4205321672
- Cited by
- 807
- References
- 7
- Citations by year
- 2026: 35 · 2025: 87 · 2024: 113 · 2023: 202 · 2022: 339 · 2021: 31
- FWCI
- 90.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Funders
- National Institute for Health and Care Research (NIHR201395)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- COVID-19 vaccines, vaccine effectiveness, waning immunity, ChAdOx1 nCoV-19 vaccine, BNT162b2, SARS-CoV-2 variants, B.1.1.7 Alpha variant, B.1.617.2 Delta variant, hospitalization, COVID-19 mortality, older adults
- MeSH terms
- Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, Vaccine Efficacy, BNT162 Vaccine, ChAdOx1 nCoV-19, Adolescent, Adult, Age Factors, Aged, Female, United Kingdom, Hospitalization, Humans, Immunization, Secondary, Male, Middle Aged, Risk Factors, Time Factors, Case-Control Studies, Patient Acuity
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