BACKGROUND: The potential cross-protective effect of measles, mumps, and rubella (MMR) vaccination against coronavirus disease 2019 (COVID-19) is debated. Although immunological studies suggest cross-reactivity between MMR-induced immunity and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), epidemiological evidence remains inconclusive. This study examined the association between an additional MMR dose and both COVID-19 clinical and serological outcomes in an adult cohort with verified pre-pandemic measles immunity. METHODS: In 2019, prior to the COVID-19 pandemic, 3027 healthcare workers from a Czech university hospital underwent measles serology testing. Seronegative individuals were offered a single additional MMR dose. Between 2020 and 2021, 261 individuals from the original sample subsequently contracted COVID-19 and underwent post-infection SARS-CoV-2 immunoglobulin G (IgG) serology testing, having remained unvaccinated against COVID-19 until that time. RESULTS: Among 212 women and 49 men (mean age: 42.7 years), 150 were measles-seropositive (without additional vaccination) and 111 were measles-seronegative but received an additional MMR dose. Following COVID-19, 216 participants (82.8 %) exhibited SARS-CoV-2 IgG seropositivity. No significant relationship was observed between measles immunity or MMR vaccine administration and COVID-19 clinical characteristics. However, individuals who received an additional MMR dose were significantly more likely to develop SARS-CoV-2 IgG seropositivity (88.3 % vs. 78.7 %; p = 0.042). Regression analysis confirmed additional MMR vaccination as an independent predictor of post-COVID-19 seropositivity (odds ratio 1.81, 95 % confidence interval 1.17-2.81, p = 0.008), irrespective of the interval between MMR vaccination and COVID-19 symptom onset. No correlation was found between pre-pandemic measles antibody titers and SARS-CoV-2 antibody levels (r = 0.09, p = 0.246). CONCLUSION: While no protective effect of adult MMR vaccination on COVID-19 clinical outcomes was observed, a significant immunological interaction was identified. These findings align with the concept of trained immunity and warrant further investigation.

Department of Microbiology University Hospital Olomouc Faculty of Medicine and Dentistry Palacký University Olomouc Hněvotínská 3 77900 Olomouc Czech Republic

Department of Occupational Medicine University Hospital Olomouc Faculty of Medicine and Dentistry Palacký University Olomouc Zdravotníků 248 7 77900 Olomouc Czech Republic

Department of Public Health Faculty of Medicine and Dentistry Palacký University Olomouc Hněvotínská 3 77900 Olomouc Czech Republic

Department of Statistics and Probability Faculty of Informatics and Statistics Prague University of Economics and Business Churchill Square 1938 4 13067 Prague Czech Republic

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