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Coronaviruses

COVID-19 Breakthrough Infections: Risk Factors and Statistics

Strategic Insights

— 1 min read

Research conducted at Vall d'Hebron Hospital Universitari in Barcelona, Spain, has identified risk factors for COVID-19 breakthrough infections after vaccination. A case-control test-negative design study analyzed 1,340 breakthrough SARS-CoV-2 infections and 4,016 controls. The findings revealed that patients who received their last vaccine dose more than six months before hospitalization had a 64% higher risk of breakthrough infection compared to those vaccinated within the previous six months.

Key Takeaways:

  • The odds of breakthrough infection were 64% higher in patients whose last vaccine dose was administered more than 6 months before hospitalization (aOR 1.64; CI 95% 1.42-1.88).
  • Immunization was not sufficient to prevent breakthrough infections, particularly in patients with immunosuppression.
  • The probability of breakthrough SARS-CoV-2 infection was significantly higher in hospitalized patients who had received their last vaccine dose more than six months before hospitalization.
  • Immunosuppression was identified as the most important risk factor for breakthrough infection (aOR 2.04; CI 95% 1.58-2.62).
  • The study highlights the need for boosters or re-vaccination for individuals who have not received their last vaccine dose within the past six months.
  • The research emphasizes the importance of maintaining a strong immune response against SARS-CoV-2, especially in immunosuppressed individuals.
  • The study was conducted between 1 November 2021 and 28 June 2022, with a total of 5,356 participants.

Statistics:

  • 1,340 breakthrough SARS-CoV-2 infections were analyzed in the study.
  • 4,016 controls were matched with the cases by age and date of test.
  • The study had a case-control test-negative design, with a total of 5,356 participants.
  • A logistic regression model with adjusted odds ratios was performed to determine factors related to breakthrough infection.
  • The study concluded that immunosuppression was statistically associated with breakthrough infection (aOR 2.04; CI 95% 1.58-2.62).

Sources:

  • Risk factors of COVID-19 breakthrough infection: a case-control test-negative design study. BMC Infectious Diseases, 2025;25(1):1346.
  • Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Hospital Universitari, Passeig Vall d'Hebron 119-129, Barcelona, 08035, Spain.
  • Medical Letter on the CDC & FDA. November 2, 2025; p 88.

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