Risk factors of COVID-19 breakthrough infection: a case-control test-negative design study

We aimed to identify risk factors for breakthrough SARS-CoV-2 infection after at least one dose of any COVID-19 vaccine. This is a case-control test-negative design study in hospitalized patients with a severe acute respiratory infection, at least one dose of any COVID-19 vaccine and a PCR-test for SARS-CoV-2/COVID-19 performed between 1 November 2021 and 28 June 2022. Cases and controls were matched by age and date of test. A logistic regression model with adjusted odds ratios was performed to determine factors related to breakthrough infection. We analyzed 1,340 breakthrough SARS-CoV-2 infections matched with 4,016 controls. After adjustment, the odds of a breakthrough infection were 64% higher in patients whose last vaccine dose was administered more than 6 months before hospitalization compared to those vaccinated within the previous 6 months (aOR 1.64; CI 95% 1.42–1.88). Moreover, immunosuppression was statistically associated with breakthrough infection (aOR 2.04; CI 95%, 1.58–2.62). 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; while immunosuppression was the most important risk factor for breakthrough infection.