Effectiveness of mRNA-1273 against asymptomatic infection, COVID-19 diagnosis, and severe outcomes

A Moderna phase 3 trial in Southern California provides evidence that the RNA-1273 vaccine is highly effective in preventing disease following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study: Real-World Effectiveness of the mRNA-1273 Vaccine Against COVID-19: Interim Results from a Prospective Observational Cohort Study. Image Credit: Seda Yalova/ Shutterstock


In response to the coronavirus disease 2019 (COVID-19) pandemic vaccines were rapidly developed. Initially, Pfizer and Moderna developed vaccines on the messenger ribonucleic acid (mRNA) platform, which proved to be successful in reducing the rates of hospitalization and death due to severe or critical COVID-19.

In their phase 3 clinical trials conducted under controlled conditions, both vaccines showed 94% and 95% efficacy against symptomatic disease, respectively. However, real-world effectiveness could differ from these experimental conditions and is crucial to understand when formulating vaccination policy.

Earlier research showed that mRNA-1273 showed 82-100% vaccine efficacy (VE) against infection with SARS-CoV-2 and 86-96% against severe COVID-19. The vaccine continued to show 100% and 96% efficacy against the alpha and beta variants, respectively.

Even as billions of doses are planned to be rolled out globally over the coming months, an interim analysis was conducted in Southern California to assess the effectiveness of the Moderna vaccine mRNA-1273 in real-world conditions. The study is part of the vaccine manufacturer’s commitment to many health authorities across the world.

The study included over 350,000 adults aged 18 years and upwards, matched against a similar number of controls. The individuals included healthcare workers, long-term care residents, workers in childcare, education, emergency services, and both younger and older adults.

The participants all received two doses of the vaccine at an interval of 24 days. Both groups were then followed up for the incidence of SARS-CoV-2 infection, disease severe enough to merit hospitalization and death.

Fewer people in this group had a history of COVID-19 before vaccination, compared to the unvaccinated group, and the median income in this group was higher than the other.

A preprint version of the study is available on Preprints with the Lancet*, while the article undergoes peer review.

What did the study show?

The investigators found that the vaccine prevented 87% of COVID-19 diagnoses in the vaccination group. There were 2.7 per 1,000 infections in the vaccinated group vs. 20 per 1,000 in the unvaccinated group.

Hospitalizations in the vaccinated group were also observed, at 0.12 per 1,000 vs. 3.2 per 1,000 in the unvaccinated group. Deaths in the two cohorts were 0.01 and 0.44 per 1,000, respectively. Therefore, the vaccine prevented nearly 96% of hospitalizations and 98% of hospital deaths related to the virus.

It was more effective in preventing symptomatic disease, at 88%, compared to nearly 73% of asymptomatic disease. No significant differences were noted by sex, age, and ethnicity.

Fewer asymptomatic infections were reported, while adults over 65 years reported more infections, as did Black and Hispanic individuals.

Among those with a history of prior infection, vaccine efficacy was between 8% and 33.6%.

Breakthrough infections among the vaccine recipients were caused by the delta variant in almost half the cases, with alpha variants responsible in just over a fifth. The gamma variant was identified in just over a tenth.

Conversely, in the unvaccinated population, the alpha variant caused 41% of infections, followed by the epsilon and delta/gamma variants in almost a fifth each. These results may be affected by the difficulty in isolating viable viruses from fully vaccinated individuals, who are more likely to have very low viral loads.

What are the implications?

The current study is among the first prospective cohort studies of the mRNA-1273 vaccine in a diverse and real-world population. It shows that the vaccine is effective against COVID-19 diagnosis, hospitalization, and death, with higher protection against symptomatic disease. This agrees with earlier studies showing that the vaccine is more protective against severe COVID-19.

In those with a prior history of natural infection, the vaccine shows some added protection. Ultimately, longer follow-up studies are required to confirm lower vaccine effectiveness among those who had been previously infected with COVID-19 and to evaluate the vaccine’s effectiveness in question against emerging variants.

*Important notice


Preprints with The Lancet publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

  • Bruxvoort, K. et al. (2021) “Real-World Effectiveness of the mRNA-1273 Vaccine Against COVID-19: Interim Results from a Prospective Observational Cohort Study”, SSRN Electronic Journal. doi: 10.2139/ssrn.3916094.
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