Protection against symptomatic infection with delta (B.1.617.2) and omicron (B.1.1.529) BA.1 and BA.2 SARS-CoV-2 variants after previous infection and vaccination in adolescents in England, August, 2021–March, 2022: a national, observational, test-negativ


Little is known about protection against SARS-CoV-2 infection following previous infection with specific individual SARS-CoV-2 variants, COVID-19 vaccination, and a combination of previous infection and vaccination (hybrid immunity) in adolescents. We aimed to estimate protection against symptomatic PCR-confirmed infection with the delta (B.1.617.2) and omicron (B.1.1.529) variants in adolescents with previous infection, mRNA vaccination, and hybrid immunity.


We conducted an observational, test-negative, case-control study using national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England. Symptomatic adolescents aged 12–17 years who were unvaccinated or had received primary BNT162b2 immunisation at symptom onset and had a community SARS-CoV-2 PCR test were included. Vaccination and previous SARS-CoV-2 infection status in adolescents with PCR-confirmed COVID-19 (cases) were compared with vaccination and previous infection status in adolescents who had a negative SARS-CoV-2 PCR test (controls). Vaccination data were collected from the National Immunisation Management System, and were linked to PCR testing data. The primary outcome was protection against SARS-CoV-2 delta and omicron infection (defined as 1 – odds of vaccination or previous infection in cases divided by odds of vaccination or previous infection in controls).


Between Aug 9, 2021, and March 31, 2022, 1161704 SARS-CoV-2 PCR tests were linked to COVID-19 vaccination status, including 390 467 positive tests with the delta variant and 212 433 positive tests with the omicron variants BA.1 and BA.2. In unvaccinated adolescents, previous SARS-CoV-2 infection with wildtype, alpha (B.1.1.7), or delta strains provided greater protection against subsequent delta infection (>86·1%) than against subsequent omicron infection (<52·4%); previous delta or omicron infection provided similar protection against omicron reinfection (52·4% [95% CI 50·9–53·8] vs 59·3% [46·7–69·0]). In adolescents with no previous infection, vaccination provided lower protection against omicron infection than against delta infection, with omicron protection peaking at 64·5% (95% CI 63·6–65·4) at 2–14 weeks after dose two and 62·9% (60·5–65·1) at 2–14 weeks after dose three, with waning protection after each dose. Adolescents with hybrid immunity from previous infection and vaccination had the highest protection, irrespective of the SARS-CoV-2 strain in the primary infection. The highest protection against omicron infection was observed in adolescents with vaccination and previous omicron infection, reaching 96·4% (95% CI 84·4–99·1) at 15–24 weeks after vaccine dose two.


Previous infection with any SARS-CoV-2 variant provided some protection against symptomatic reinfection, and vaccination added to this protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provided the most robust protection. Although more data are needed to investigate longer-term protection and protection against infection with new variants, these data question the need for additional booster vaccine doses for adolescents in populations with already high protection against SARS-CoV-2 infection.

Author list



  1. Public Health Programmes, UK Health Security Agency, London, UK
  2. National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation, London School of Hygiene & Tropical Medicine, London, UK 
  3. NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK
  4. Paediatric Infectious Diseases Research Group, St George’s University of London, London, UK


Annabel A Powell, Freja Kirsebom, Julia Stowe, Mary E Ramsay, Jamie Lopez-Bernal, Nick Andrews*, Shamez N Ladhani*

Novel Coronavirus SARS-CoV-2


The Lancet - Infectious Diseases