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Review 2: "Efficacy of the Measles-Mumps-Rubella(MMR) Vaccine in the Reducing the Severity of COVID-19: An Interim Analysis of a Randomised Controlled Clinical Trial"

This preprint claims that the MMR vaccine offers some protection against COVID-19, but does not decrease risk of infection. While the claims are potentially informative and supportive of similar studies, large potential biases exist in the study that need to be addressed.

Published onOct 21, 2021
Review 2: "Efficacy of the Measles-Mumps-Rubella(MMR) Vaccine in the Reducing the Severity of COVID-19: An Interim Analysis of a Randomised Controlled Clinical Trial"
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ABSTRACTBackgroundCOVID-19 is still a challenge, both with regard to its treatment and to the actual efficacy of the vaccines available to date, especially with the emergence of new variants. We evaluated the efficacy of the measles-mumps-rubella (MMR) vaccine in preventing SARS-CoV-2 infection and severity of COVID-19 in health workers.MethodsThis analysis includes data from one ongoing blinded, randomized, placebo-controlled trial with participants aged 18-60 years were randomly assigned to receive the MMR vaccine or a placebo. The primary efficacy analysis included all participants with a positive nasopharyngeal RT-PCR test since their inclusion.ResultsThe MMR vaccine did not prevent the SARS-CoV-2 infection. Participants in the MMR group, compared with those in the placebo group, had a 48% risk reduction in symptomatic COVID-19 (RR = 0.52; 95% CI: 0.33–0.83; p=0.004) and a 76% risk reduction in COVID-19 treatment (RR = 0.24; 95% CI: 0.06 – 0.88; p = 0.020) with one dose and a 51% risk reduction in COVID-19 symptoms (RR = 0.49; 95% CI: 0.31 – 0.78; p = 0.001) and a 78% risk reduction in COVID-19 treatment (RR = 0.22; 95% CI: 0.06 – 0.82; p = 0.015) with two doses.ConclusionsThis interim analysis of an ongoing clinical trial suggests that compared with a placebo, the vaccine reduces the risk of COVID-19 symptoms and reduces the need for COVID-19 treatment.Clinical Trials RegistryBrazilian Clinical Trials Registry (ReBEC n° RBR-2xd6dkj - MMR vaccine can stimulate the innate immunity inducing a nonspecific protection against other infections, called heterologous immunity.Repeated exposure to the antigen (innate immune response training) results in an extension of the action time of this immune response (innate immune response memory) and consequently in protection against other infections (heterologous immunity) for a longer time.The MMR vaccine has been used by national immunization programs in the world for many years, it is very safe and can be stored and distributed at 2-8°C, making it particularly suitable for global distribution.Among participants who received at least one dose, compared with those in the placebo group, participants in the MMR group had a significant risk reduction in symptomatic COVID-19 and of cases requiring treatment.The use of MMR vaccine can be useful in several populations in the world that do not have access to the COVID-19 vaccine and in a future epidemic or pandemic as an emergency measure until specific treatments or vaccines for each case are available to the general population.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.


Review: The measles-mumps-rubella (MMR) vaccine has been hypothesized to offer protection against coronavirus disease 2019 (COVID-19) in several clinical studies since spring 2020.(1–3). To confirm this hypothesis the authors designed a randomized, double-blind, placebo-controlled, phase 3, clinical trial to evaluate efficacy of the MMR vaccine against SARS-CoV-2 in 430 health workers. They conclude that “the MMR vaccine can significantly decrease the rate of symptomatic COVID-19 and of cases requiring treatment.” I consider the claims in this study reliable based on the methods and data reported. Regarding their results, MMR does not reduce the risk infection, as suggested in previous studies(1). These findings could explain one of the major unknowns of the Covid-19 pandemic, why most of the infected children and young adults presented with asymptomatic or mild forms of Covid-19. Rather, we wonder if the partial protection against SARS-CoV-2 observed in MMR-vaccinated youths could explain the rapid spread of the virus through asymptomatic carriers. In addition, information on participants childhood MMR vaccination history would be of great interest. I also recommend a multivariate statistical analysis by sex, age, co-morbidities, and MMR vaccination status. They also claim that the MMR vaccine would be useful in several populations in the world that do not have access to the COVID-19 vaccine. Although great efforts are being made to develop specific vaccines against SARS-CoV-2 in record time, and even if these vaccines development have received all the institutional support, it is probable that they will not reach the third world for several years. Today, many thousands of children continue to die in Africa from measles. Furthermore, many authors have warned of the difficulties of developing MMR vaccination campaigns this year due to the Covid-19 pandemic(4). We consider that the World Health Organization (WHO) should see their results as an opportunity to guarantee the access of the MMR vaccine in the third world, not only to protect from measles, but from Covid-19 as well. Considering the significance of these reported results, despite the methodological deficiencies and limitations declared by the authors, I strongly recommend accepting this paper.

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