Conclusions
The current evidence base on messenger RNA (mRNA) vaccines is made up entirely of small early-stage trials, nearly all of which
examined only short-term outcomes. They lack sufficient power for testing the statistical significance of most results, and for
assessing the risk of serious but uncommon adverse events.
The size of these trials and their dual purpose in evaluating dosing and safety precludes quantitative synthesis or GRADE analysis of
their results, but there are a few trends that appear to be consistent across the different studies. Systemic adverse effects such as
fatigue, headache, muscle aches, and chills are common following administration of mRNA vaccines, but they usually resolve within a
day or two. Localized adverse effects, most notably pain at the injection site, are also common, and also resolve within a day or two.
The rate of severe adverse effects (severe enough to interfere with a person’s daily activities) appears to be in the range of 5 to 10
percent. The rate and severity of adverse events increases with vaccine dose. The rate and severity of adverse events also appears to
be greater following a second dose of vaccine than following the first.
Larger clinical trials of mRNA vaccines against the SARS-CoV-2 coronavirus are in progress, and their results are expected in mid-2021. Once evidence from those trials is published, more certain conclusions about the safety of these vaccines may be reached.
Additional trials will be necessary to determine the relative safety of mRNA vaccines and vaccines using more established
technologies.
Clinical guidance specific to the use of mRNA vaccines is lacking at this time, because of the lack of clinical evidence.