The objective of this study was to assess the local and systemic adverse reactions after the administration of a COVID-19 mRNA-1273 booster between December 2021 and February 2022 by comparing the type of mRNA vaccine used as primary series (mRNA-1273 or BNT162b2) and homologous versus heterologous booster in health care workers (HCW). A cross-sectional study was performed in HCW at a tertiary hospital in Barcelona, Spain. A total of 17% of booster recipients responded to the questionnaire. The frequency of reactogenicity after the mRNA-1273 booster (88.5%) was similar to the mRNA-1273 primary doses (85.8%), and higher than the BNT162b2 primary doses (71.1%). The reactogenicity was similar after receiving a heterologous booster compared to a homologous booster (88.0% vs. 90.2%, p = 0.3), and no statistically significant differences were identified in any local or systemic reactions. A higher frequency of medical leave was identified in the homologous booster dose group vs. the heterologous booster dose group (AOR 1.45; 95% CI: 1.00–2.07; p = 0.045). Our findings could be helpful in improving vaccine confidence toward heterologous combinations in the general population and in health care workers.

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.