Measles-mumps-rubella booster and post-COVID-19 immunity: A retrospective cohort study

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.

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.

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).

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.