Safety and efficacy of Pfizer and AstraZeneca COVID-19 vaccines even better than clinical trials predicted

By Sally Robertson, B.Sc.Apr 28 2021

Researchers in the UK and United States have demonstrated the efficacy of one dose of either the Pfizer-BioNTech or Oxford-AstraZeneca vaccine against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a real-world community setting in the UK.

The novel SARS-CoV-2 virus is the agent responsible for the coronavirus disease 2019 (COVID-19) pandemic that continues to pose a threat to global public health and has now claimed the lives of more than 3.1 million people worldwide.

The large prospective observational study of more than 627,000 individuals found that self-reported infection rates among participants who received either vaccine were significantly lower than among unvaccinated controls.

As reported in The Lancet: Infectious Diseases, documented infection rates following a single dose of the Pfizer-BioNTech (BNT162b2) vaccine were 58% lower after 12 to 20 days, 69% lower after 21 to 44 days, and 72% lower after 45 to 59 days, compared with unvaccinated controls.

Following one dose of the Oxford-AstraZeneca (ChAdOx1) vaccine, documented infection rates were 39% lower after 12 to 20 days and 60% lower after 21 to 44 days than among unvaccinated controls.

Furthermore, reported side-effects following vaccination were moderate in frequency, minor in severity, and of short duration, reports Cristina Menni from King’s College London and colleagues.

“Our data support results from randomized controlled trials in a large community-based scenario showing evidence of reduction in infection after 12 days and substantial protection after 3 weeks,” writes the team.

Study: Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study

UK government decided to delay second vaccine doses

In the UK, the rollout of the Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines began on the 8^th of December 2020 and the 4^th of January 2021, respectively.

Based on advice from the Joint Committee on Vaccination and Immunization, the UK Government decided in late December 2020 to delay the administration of second doses.

Phase 3 trials have reported efficacy of 52% twelve days following a first dose of the BNT162b2 vaccine and 95% following administration of a second dose 3 to 4 weeks later.

However, a reanalysis of the effectiveness data reported for BNT162b2 in reducing infection, severe disease, hospitalization, and death across the whole of Israel revealed an efficacy of 90% two weeks following just the one dose.

A clinical trial of the ChAdOx1 vaccine also reported efficacy against symptomatic COVID-19 of 76% just 22 days following one dose.

However, surveillance within the general UK population is needed at this stage of vaccination rollout to assess the safety and effectiveness of these vaccines in the real-time community setting, says Menni and colleagues.

What did the study involve?

The team investigated self-reported adverse effects among 627,383 individuals (aged 16 to 99 years) who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 vaccines between December 8^th, 2020 and March 10^th, 2021.

Participants self-reported side effects in real-time via the COVID Symptom Study app.

The researchers also compared infection rates among a subset of 103,622 vaccinated individuals who subsequently logged at least one PCR or lateral flow test with rates among 464,356 unvaccinated app users who also logged these test results.

What did the study find?

Of the 627,383 vaccinated individuals, 282,103 received one dose of BNT162b2, of whom a further 28,207 received a second dose, and 345,280 received one dose of ChAdOx1.

The most commonly reported systemic side-effects following vaccination were fatigue and headache, which lasted for a mean of 1·01 days. The most commonly reported local side effects were tenderness and pain at the injection site, which lasted a mean of 1·02 days.

A significantly higher proportion of the individuals who received one dose of ChAdOx1 reported systemic side effects, compared with those who received one dose of BNT162b2, at 33.7% versus 13·5%.

By contrast, local side effects were less frequently reported after one dose of ChAdOx1 than after one dose of BNT162b2, at 58·7% versus 71·9%

Systemic side effects were 1·6 times more common after one dose of ChAdOx1 and 2·9 times more common after one dose of BNT162b2 among individuals with previous SARS-CoV-2 infection than among those without previous infection.

Local effects were similarly more common among individuals with previous infection than among those without (1·4 times more common after one dose of ChAdOx1 and 1·2 times more common after one dose of BNT162b2).

What about the SARS-CoV-2 infection rate?

In the subset of participants who logged PCR or lateral flow test results, 3,106 (0.03%) of 103,622 vaccinated individuals tested positive for SARS-CoV-2 infection, compared with 50,340 (9.22%) of the 464,356 unvaccinated controls.

The team observed significant reductions in infection risk starting from day 12 following one vaccine dose, reaching 60% for ChAdOx1 and 69% for BNT162b2 after 21 to 44 days and 72% for BNT162b2 after 45 to 59 days.

The researchers say that although the observational nature of these data do not directly reflect effectiveness, the observed decrease in infection over time following one vaccine dose supports the UK Government’s decision to delay the timing of a second dose to 12 weeks to maximize the number of people who receive at least one dose.

However, long-term surveillance for SARS-CoV-2 protection in individuals who have received delayed second doses compared with those receiving second doses according to initial guidelines (21 days after the first dose) will be required to determine whether these initial protection estimates persist, concludes the team.