by Dr. Juliette Dufour
For December 2021, we have selected: S.J. Thomas et al, Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months. N Engl J Med. 2021 Nov 4;385(19):1761-1773. doi: 10.1056/NEJMoa2110345. Epub 2021 Sep 15.
The Covid-19 pandemic continues with recent estimates of 187 million cases diagnosed and four million deaths. Fortunately, vaccines are now available and approved; BNT162b2 is one of them. BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Today, more than a billion doses have been distributed in the world.
A previous study published data on safety and efficacy at two months postimmunisation involving patients older than 16 years: vaccine efficacy was 95% and the safety profile was good. The authors here continued the follow-up and added data on 12 to 15-year-old children, in order to provide an update about safety and efficacy findings after six months of follow-up.
Our authors of the month conducted a randomised, placebo-controlled, observer-blinded, multinational study to assess the safety, efficacy and immunogenicity of the BNT162b2 vaccine. Eligible were all patients, healthy or with stable chronic disease, older than 12 years, who had received the BNT162b2 vaccine. Excluded were participants with an active immunocompromising condition or who had had recent immunosuppressive therapy. Participants with a history of Covid-19 were excluded but evidence of previous infection by SARS-CoV-2 on laboratory test were not an exclusion criterion.
A total of 44,165 patients from 152 sites were randomised with a 1:1 ratio to receive two intramuscular injections, 21 days apart, of either the vaccine (30 µg) or a saline placebo. Those who had been randomly assigned to receive the placebo were offered the vaccine after unblinding. Ninety-eight per cent (43,409) of patients received two doses.
This trial had two end points: safety and efficacy. Safety endpoints included (i) prespecified local reactions, systemic events and medication use during the first seven days after each injection; (ii) unsolicited adverse events through one month after the second dose; (iii) serious adverse events through six months after the second dose. Efficacy was assessed in patients without virologic evidence of SARS-CoV-2 with an onset of seven days or more after the second dose.
Safety
Cumulative safety data after six months follow-up were available for 12,006 participants assigned to the BNT162b2 group. No new safety signals were observed. In total, 34 patients died, none of these deaths were related to BNT162b2 according to the investigators.
In the subgroup evaluated for reactogenicity, the profile did not differ from that described previously. More participants in the BNT162b2 group than in the placebo group reported local reactions and notably mild to moderate pain at the injection site, but also systemic events such as fatigue. Notably, patients in the BNT162b2 group that had evidence of previous infection reported more systemic events after the first dose but fewer after the second dose than the placebo group.
Efficacy
- Among the 42,094 patients who had no evidence of previous SARS-CoV-2 infection, the vaccine efficacy was 91.3% [89-93.2].
- Among the 44,486 participants with or without previous infection, vaccine efficacy was 91.1% [88.8-93].
- Vaccine efficacy in severe Covid-19 was 96.7% [80.3-99.9].
- Previous infection conferred approximately 72.6% protection.
- After the first dose, vaccine efficacy was 58.4% [40.8-71.2]; this efficacy raised with time and the peak (91.7%) was obtained between 11 days after the first injection and the second dose. Then vaccine efficacy declined: 96.2% from seven days to two months after the second dose; 90.1% from two and four months after the second dose; 83.7% four months after the second dose.
Our authors of the month concluded that the benefit of BNT162b2 immunisation started approximately 11 days after the first dose and then gradually decreased with an average of 6% every two months. Ongoing follow-up is needed to understand the persistence of vaccine effect over time and the need for booster dosing. Efficacy was observed seven days after the first injection and so across diverse demographic profiles (age, sex, high BMI) and diverse geographic regions.
Regarding the variants, the authors studied in-vitro variants, and all were neutralised by the vaccine; moreover, vaccine efficacy in south Africa where the beta variant is predominant was 100%.
In conclusion, this paper of the month shows that BNT162b2 prevents Covid effectively for up to six months after the second dose despite the emergence of variants, and the vaccine continues to show a favourable safety profile.
