BACKGROUND AND PURPOSE: 

• Antonelli et al. (Lancet Infectious Diseases, 2021) identified risk factors for post-vaccination “breakthrough” SARS-CoV-2 infection and characteristics of post-vaccination illness 

METHODS:

• Prospective, community-based, nest, case-control study 
• Population 
  • Adult users of the COVID Symptom Study app in the UK  
  • No prior positive COVID-19 test 
• Exposures 
  • Group 1 
    • Vaccinated, with a COVID-19 test at least 14 days after their first vaccination (but before their second) 
  • Group 2 
    • Vaccinated, with a test at least 7 days after their second vaccination 
  • Group 3 
    • Group 1, but users who used the app for at least 14 consecutive days after testing positive 
  • Group 4 
    • Group 2, but users who used the app for at least 14 consecutive days after testing positive 

• Study design 
  • Cases: Those with positive tests  
  • Controls: Those with negative tests 
  • 1:1 matching 
    • The date of the post-vaccination test 
    • Health-care worker status 
    • Sex 
    • BMI (for group 3 and 4) 
    • Age (for group 3 and 4) 
  • Univariate logistic regression models (adjusted for age, BMI, and sex) were used to analyze the associations of outcomes and vaccination status 
• Primary outcomes 
  • Individual symptoms 
  • Overall disease duration 
  • Disease severity 

RESULTS:

Risk factor analysis 

• 1,240,009 reported a first vaccine dose | 971,504 reported a second dose 
  • Positive COVID-19 tests after first dose: 0.5% 
  • Positive COVID-19 tests after second dose: 0.2% 
• Risk factors associated with breakthrough infection following the first dose 
  • Frailty in older adults (≥60 years) 
    • Odds ratio 1.93 (95% CI, 1.50 to 2.48); P<0.0001 
  • Living in highly deprived areas 
    • OR 1.11 (95% CI, 1.01 to 1.23); P=0.039 
• BMI: Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose 
  • OR 0.84 (95% CI, 0.75 to 0.94); P=0.0030 

Disease profile analysis 

• Vaccination (vs no vaccination) was associated with reduced odds of 
  • Hospitalization 
  • Having >5 symptoms in the first week of illness following the first or second dose 
  • Long-duration (≥28 days) symptoms following the second dose 
• Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals 
• Vaccinated participants were more likely to be completely asymptomatic, especially if they were ≥60 years  

CONCLUSION:

• Breakthrough infections remain rare in vaccinated individuals, but frail older adults, individuals living in deprived areas and those with obesity are at higher risk  
  • The authors suggest that these higher risk individuals might represent populations best suited for “booster” doses 
• The authors state

We found that the odds of having symptoms for 28 days or more after post-vaccination infection were approximately halved by having two vaccine doses 

This result suggests that the risk of long COVID is reduced in individuals who have received double vaccination, when additionally considering the already documented reduced risk of infection overall 

Lancet Infectious Diseases, 2021

Learn More – Primary Sources

Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study 

Related ObG Topics:

How does Vaccination Impact Viral Load and Duration of Illness in Those with Breakthrough SARS-CoV-2 Infection?

The Value of Vaccination for Those Previously Infected with SARS-CoV-2

mRNA-Based COVID-19 Vaccines Induce Robust, Persistent Immune Responses in Humans