Newly published data shows just 0.6% of patients receiving the Moderna mRNA vaccine reported serious adverse events, a rate identical to that of the placebo group.
Moderna’s coronavirus disease 2019 (COVID-19) vaccine showed a 94.1% efficacy rate in its phase 3 trial, and serious adverse events were rare, occurring in just 0.6% of patients in both the vaccine and placebo groups.
The US Food and Drug Administration (FDA) gave emergency use authorization to the vaccine, named mRNA-1273, back on December 18; the data used to support the approval were published Dec. 30 in the New England Journal of Medicine.
The vaccine, the second approved for emergency use in the United States, is an mRNA-based vaccine that encodes the perfusion stabilized full-length spike protein of the SARS-CoV-2 virus and is encapsulated in a lipid nanoparticle. It is administered in a 100 μg injection, with two doses given 28 days apart.
The study was designed to compare the risk of COVID-19 infection among those with and without the vaccine. Cases with symptom onset at least 14 days after the second injection in patients who had not previously been infected were considered to be new infections.
The study had an enrollment of 30420 patients, divided equally, with half receiving the vaccine and half receiving placebo. Of the total enrolled, 2.2% had evidence of SARS-CoV-2 infection at the start of the study, and 96% of patients received both injections.
Following administration of both injections, just 11 patients in the trial’s vaccine arm were confirmed to have symptomatic COVID-19, a rate of 3.3 per 1000 person-years. In the placebo group, 185 participants became infected with the virus, a rate of 56.5 per 1000 person-years.
Just 30 patients developed severe COVID-19, and only one patient died; all of the patients with severe disease were in the placebo group.
The vaccine was developed on a rapid timetable, with the study launching in July 2020. The cutoff for data collection was November 21, 2020.
While the efficacy data were impressive, much of the attention surrounding COVID-19 vaccine research has focused on safety data. Some fear the short development timetable and considerable public pressure for regulators to approve a vaccine could obscure potential safety risks.
However, the early data from the mRNA-1273 trial suggest significant adverse effects were very rare.
While injection-site solicited adverse events, mostly grades 1 and 2, occurred in more than 80% of patients in the vaccine group following both doses, those symptoms went away within 2 to 3 days. Delayed injection-site reactions occurred in just 0.8% of patients following the first dose and 0.2% of patients following the second dose, and those resolved within 4 to 5 days.
Solicited systemic adverse events were less common than injection-site events, with 54.9% of patients in the vaccine group reporting such events following the first dose, and 79.4% reporting the events following the second dose. In the placebo group, solicited systemic adverse events were reported in 42.2% of patients after the first dose and 36.5% of patients following the second dose.
Unsolicited adverse event reports were similar in both groups. A total of 5 deaths were reported between the placebo and vaccine groups. Of the 2 deaths reported in the vaccine group, one was due to cardiopulmonary arrest and the other was a suicide.
Grade 3 adverse events were reported in 1.3% of patients in the placebo group and 1.5% of patients in the vaccine group. Medically attended adverse events occurred in 9.7% of the placebo group and 9.0% of the vaccine group, and serious adverse events occurred in 0.6% of both groups.
“Overall, the safety of the mRNA-1273 vaccine regimen and platform is reassuring,” wrote corresponding author Hana M. El Sahly, MD, of the Baylor College of Medicine, and colleagues. “[N]o unexpected patterns of concern were identified.”
The authors said the data must be put in context, coming amid shifting infection trajectories over the summer, and in an environment where many local governments were requiring social distancing, mask-wearing, and other infection-control tactics. The investigators said the fact that none of the severe cases of COVID-19 were reported in the vaccine group is an encouraging finding. The research team will continue collecting follow-up data and assessing changes in efficacy over time, as the study is ongoing.