Research Open Access
Like 0



In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.


Using a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.


Individuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.


Overall VE was 74% (95% CI: 69–79), 76% (95% CI: 71–80), 63% (95% CI: 48–75) and 63% (95% CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥ 75 years, respectively. VE among those aged 30–59 years was 78% (95% CI: 75–81), 66% (95% CI: 58–73), 91% (95% CI: 87–94) and 52% (95% CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52–77), 65% (95% CI: 48–76) and 83% (95% CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30–59 years was 87% (95% CI: 83–89) at 14–29 days and 65% (95% CI: 56–71%) at ≥ 90 days between vaccination and onset of symptoms.


VE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.


Article metrics loading...

Loading full text...

Full text loading...



  1. World Health Organization (WHO). COVID-19 Weekly Epidemiological Update. Edition 56. Geneva: WHO; 2021. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20210907_weekly_epi_update_56.pdf?sfvrsn=525616e9_4&download=true
  2. European Centre for Disease Prevention and Control (ECDC), World Health Organization Regional Office for Europe (WHO/Europe). Assessing SARS-CoV-2 circulation, variants of concern, non-pharmaceutical interventions and vaccine rollout in the EU/EEA, 16th update. Stockholm: ECDC; 2021. Available from: https://www.ecdc.europa.eu/sites/default/files/documents/covid-19-rapid-risk-assessment-16th-update-september-2021.pdf
  3. Nextstrain. Genomic epidemiology of SARS-CoV-2 with Europe-focused subsampling. [Accessed: 30 Oct 2021]. Available from: https://nextstrain.org/ncov/gisaid/europe
  4. Shu Y, McCauley J. GISAID: Global initiative on sharing all influenza data - from vision to reality. Euro Surveill. 2017;22(13):30494.  https://doi.org/10.2807/1560-7917.ES.2017.22.13.30494  PMID: 28382917 
  5. European Medicines Agency (EMA). COVID-19 vaccines: authorised. Amsterdam: EMA. [Accessed: 28 Apr 2022]. Available from: https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/vaccines-covid-19/covid-19-vaccines-authorisedCOVID-19 vaccines
  6. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-16.  https://doi.org/10.1056/NEJMoa2035389  PMID: 33378609 
  7. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603-15.  https://doi.org/10.1056/NEJMoa2034577  PMID: 33301246 
  8. Sadoff J, Gray G, Vandebosch A, Cárdenas V, Shukarev G, Grinsztejn B, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021;384(23):2187-201.  https://doi.org/10.1056/NEJMoa2101544  PMID: 33882225 
  9. Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99-111.  https://doi.org/10.1016/S0140-6736(20)32661-1  PMID: 33306989 
  10. Rosenberg ES, Dorabawila V, Easton D, Bauer UE, Kumar J, Hoen R, et al. Covid-19 vaccine effectiveness in New York State. N Engl J Med. 2022;386(2):116-27.  https://doi.org/10.1056/NEJMoa2116063  PMID: 34942067 
  11. Martínez-Baz I, Miqueleiz A, Casado I, Navascués A, Trobajo-Sanmartín C, Burgui C, et al. , Working Group for the Study of COVID-19 in Navarra. Effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infection and hospitalisation, Navarre, Spain, January to April 2021. Euro Surveill. 2021;26(21).  https://doi.org/10.2807/1560-7917.ES.2021.26.21.2100438  PMID: 34047271 
  12. Andrews N, Tessier E, Stowe J, Gower C, Kirsebom F, Simmons R, et al. Duration of protection against mild and severe disease by Covid-19 vaccines. N Engl J Med. 2022;386(4):340-50.  https://doi.org/10.1056/NEJMoa2115481  PMID: 35021002 
  13. Poukka E, Baum U, Palmu AA, Lehtonen TO, Salo H, Nohynek H, et al. Cohort study of Covid-19 vaccine effectiveness among healthcare workers in Finland, December 2020 - October 2021. Vaccine. 2022;40(5):701-5.  https://doi.org/10.1016/j.vaccine.2021.12.032  PMID: 34953607 
  14. Skowronski DM, Febriani Y, Ouakki M, Setayeshgar S, El Adam S, Zou M, et al. Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada. Clin Infect Dis. 2022;ciac290.  https://doi.org/10.1093/cid/ciac290  PMID: 35438175 
  15. Feikin DR, Higdon MM, Abu-Raddad LJ, Andrews N, Araos R, Goldberg Y, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet. 2022;399(10328):924-44.  https://doi.org/10.1016/S0140-6736(22)00152-0  PMID: 35202601 
  16. Kissling E, Hooiveld M, Sandonis Martín V, Martínez-Baz I, William N, Vilcu A-M, et al. Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021. Euro Surveill. 2021;26(29).  https://doi.org/10.2807/1560-7917.ES.2021.26.29.2100670  PMID: 34296676 
  17. I-MOVE-COVID-19 Network. COVID-19 vaccine effectiveness at primary care level in Europe: generic protocol. Paris: Epiconcept; 2021. Available from: https://www.imoveflu.org/wp-content/uploads/2021/05/I-MOVE-COVID-19-primary-care-COVID-19-vaccine-effectiveness-protocol-v2.3.pdf
  18. Jackson ML, Nelson JC. The test-negative design for estimating influenza vaccine effectiveness. Vaccine. 2013;31(17):2165-8.  https://doi.org/10.1016/j.vaccine.2013.02.053  PMID: 23499601 
  19. Wellcome Sanger Institute. COVID–19 genomic surveillance. Hinxton: Wellcome Sanger Institute. [Accessed: 28 Oct 2021]. Available from: https://covid19.sanger.ac.uk
  20. Nextstrain. Genomic epidemiology of SARS-CoV-2 with Europe-focused subsampling. [Accessed: 28 Apr 2022]. Available from: https://nextstrain.org/ncov/gisaid/europe?f_region=Europe
  21. Harrell FE. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. New York: Springer; 2001. 568 p.
  22. Lopez Bernal J, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med. 2021;385(7):585-94.  https://doi.org/10.1056/NEJMoa2108891  PMID: 34289274 
  23. Tang P, Hasan MR, Chemaitelly H, Yassine HM, Benslimane FM, Al Khatib HA, et al. BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the SARS-CoV-2 Delta variant in Qatar. Nat Med. 2021;27(12):2136-43.  https://doi.org/10.1038/s41591-021-01583-4  PMID: 34728831 
  24. Emborg H-D, Valentiner-Branth P, Schelde AB, Nielsen KF, Gram MA, Moustsen-Helms IR, et al. Vaccine effectiveness of the BNT162b2 mRNA COVID-19 vaccine against RT-PCR confirmed SARS-CoV-2 infections, hospitalisations and mortality in prioritised risk groups. medRxiv. 202105.27.21257583. Preprint  https://doi.org/10.1101/2021.05.27.21257583 .  https://doi.org/10.1101/2021.05.27.21257583 
  25. Whitaker HJ, Tsang RSM, Byford R, Andrews NJ, Sherlock J, Sebastian Pillai P, et al. Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response amongst individuals in clinical risk groups. J Infect. 2022;84(5):675-83.  https://doi.org/10.1016/j.jinf.2021.12.044  PMID: 34990709 
  26. Thompson MG, Stenehjem E, Grannis S, Ball SW, Naleway AL, Ong TC, et al. Effectiveness of Covid-19 vaccines in ambulatory and inpatient care settings. N Engl J Med. 2021;385(15):1355-71.  https://doi.org/10.1056/NEJMoa2110362  PMID: 34496194 
  27. Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med. 2021;384(15):1412-23.  https://doi.org/10.1056/NEJMoa2101765  PMID: 33626250 
  28. Andrews N, Tessier E, Stowe J, Gower C, Kirsebom F, Simmons R, et al. Duration of protection against mild and severe disease by Covid-19 vaccines. N Engl J Med. 2022;386(4):340-50.  https://doi.org/10.1056/NEJMoa2115481  PMID: 35021002 
  29. Tartof SY, Slezak JM, Fischer H, Hong V, Ackerson BK, Ranasinghe ON, et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet. 2021;398(10309):1407-16.  https://doi.org/10.1016/S0140-6736(21)02183-8  PMID: 34619098 
  30. Bruxvoort KJ, Sy LS, Qian L, Ackerson BK, Luo Y, Lee GS, et al. Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study. BMJ. 2021;375:e068848.  https://doi.org/10.1136/bmj-2021-068848  PMID: 34911691 
  31. Halloran ME, Longini IM, Struchiner CJ. Design and analysis of vaccine studies. New York: Springer; 2010. 387 p.
  32. World Health Organisation (WHO). Evaluation of COVID-19 vaccine effectiveness. Interim guidance. Geneva: WHO; 2021. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccine_effectiveness-measurement-2021.1
  33. Kahn R, Schrag SJ, Verani JR, Lipsitch M. Identifying and alleviating bias due to differential depletion of susceptible people in postmarketing evaluations of COVID-19 vaccines. Am J Epidemiol. 2022;191(5):800-11.  https://doi.org/10.1093/aje/kwac015  PMID: 35081612 
  34. Greenwood M, Yule GU. The Statistics of anti-typhoid and anti-cholera inoculations, and the interpretation of such statistics in general. Proc R Soc Med. 1915;8(Epidem_State_Me) Sect Epidemiol State Med;113-94.  https://doi.org/10.1177/003591571500801433  PMID: 19978918 
  35. Andrews N. High vaccine coverage: Are unvaccinated at the same risk of exposure to SARS-CoV-2 as the vaccinated? How can we measure this and implications for studies? ECDC VE study workshop. Stockholm: European Centre for Disease Prevention and Control; 15 Oct 2021

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error