Data from a new real-world study has found that protection against COVID-19 is ‘waning’ in double-vaccinated individuals.

The Zoe COVID-19 Study app analysed data on positive COVID-19 PCR test results processed between May and July 2021, taken by more than one million people who had received two doses of either the Pfizer/BioNTech or AstraZeneca (AZ) vaccine.

The researchers, led by Professor Tim Spector, lead investigator on the Zoe COVID-19 Study app behind the research, found that following two doses of the Pfizer/BioNTech jab, protection fell from 88% at one month to 74% at five to six months.

For those vaccinated with the AZ vaccine, protection similarly dropped – within a slightly shorter time frame of four to five months – from 77% to 67%.

“Waning protection is to be expected and is not a reason to not get vaccinated. Vaccines still provide high levels of protection for the majority of the population, especially against the Delta variant, so we still need as many people as possible to get fully vaccinated,” said Spector.

The results follow a similar study published in August by the Office for National Statistics and the Oxford Vaccine Group. The results show that, while both vaccines were effective against the Delta variant, protection wanes over time. While Pfizer/BioNTech’s Comirnaty was 92% effective against high viral load 14 days after the second dose, it fell to 78% after 90 days. AZ’s Vaxzevria also saw a drop, from 69% effective against high viral load after 14 days to 61% after 90 days.

Pfizer and BioNTech have filed a supplemental Biologics License Application (sBLA) with the US Food and Drug Administration (FDA) for the approval of a third dose of their Comirnaty COVID-19 vaccine for those aged 16 years and older.

The news comes as US health leaders greenlight COVID-19 booster shots for all Americans in light of the “very clear” evidence that protection declines over time.

The sBLA is based on new data from a phase 3 clinical trial investigating the effect of a booster (third) dose of Comirnaty between 4.8 and 8 months after the first two doses.
Levels of neutralising titres present after the third dose were more than three times the levels of titres present after the second dose. Side effects were generally consistent with existing clinical data for Comirnaty after the first two doses.

The sBLA follows a number of studies in recent weeks that have reported that COVID-19 vaccine protection falls over time, backing up the need for boosters. While both Pfizer/BioNTech and AstraZeneca’s vaccines offer good protection, studies released this week from the Zoe COVID-19 Study show that protection could fall by up to 14%.

Top health leaders and medical experts from across the US Department of Health and Human Services have announced that all Americans will be eligible for a booster dose of the Pfizer/BioNTech or Moderna vaccines from 20 September.

A joint statement on the need for booster shots was issued by Center for Disease Control director Rochelle Walensky, Food and Drug Administration acting commissioner Janet Woodcock, US surgeon general Vivek Murthy, director of the National Institutes of Health Francis Collins, and chief medical advisor to President Biden Anthony Fauci.

“The COVID-19 vaccines authorised in the United States continue to be remarkably effective in reducing risk of severe disease, hospitalisation, and death, even against the widely circulating Delta variant,” said the group.

However, the available data makes it “very clear that protection against SARS-CoV-2 infection begins to decrease over time following the initial doses of vaccination”, they said, adding that, with the dominance of the delta variant, “we are starting to see evidence of reduced protection against mild and moderate disease”.

The latest assessment concluded that “the current protection against severe disease, hospitalisation, and death could diminish in the months ahead, especially among those who are at higher risk or were vaccinated during the earlier phases of the vaccination roll-out”.

The group of health leaders said that their top priority remained “staying ahead of the virus and protecting the American people from COVID-19 with safe, effective and long-lasting vaccines”, and once again they encouraged urgency for those who are unvaccinated to get the shots.

The FDA has officially approved the first vaccine for the prevention of COVID-19 disease in individuals 16 years and over: Pfizer/BioNTech’s Comirnaty, after 1.2 billion doses have been delivered to more than 120 countries worldwide.

“The FDA’s approval of this vaccine is a milestone as we continue to battle the COVID-19 pandemic,” said acting FDA commissioner Janet Woodcock. “As the first FDA-approved COVID-19 vaccine, the public can be very confident that this vaccine meets the high standards for safety, effectiveness and manufacturing quality the FDA requires of an approved product.”

With many of those who are vaccine hesitant citing the lack of official FDA approval as a key reason for not accepting the vaccine, Woodcock was keen to reassure people. “While millions of people have already safely received COVID-19 vaccines, we recognise that, for some, the FDA approval of a vaccine may now instil additional confidence to get vaccinated. Today’s milestone puts us one step closer to altering the course of this pandemic in the US,” she said.

Comirnaty was first approved by the FDA under an emergency use authorisation on 20 December 2020 for those 16 years and over, which was expanded on 10 May 2021 to cover 12-15 year-olds. The EUA remains in force for 12-15 year-olds.

The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has authorised Regeneron/Roche’s antibody cocktail for the treatment and prevention of COVID-19.

The conditional marketing authorisation (CMA) for Ronapreve – a combination of monoclonal antibodies casirivimab and imdevimab (known as REGEN-COV in the US) – means patients across all four nations of the UK can receive the treatment.

The combination therapy is authorised to treat and prevent COVID-19 including in people who may need ongoing monthly doses if they have a medical condition that makes them unlikely to respond to or be protected by vaccination.

UK health and social care secretary, Sajid Javid, said: “The UK is considered a world leader in identifying and rolling out life-saving treatments for COVID-19, once they have been proven safe and effective in our government-backed clinical trials. This treatment will be a significant addition to our armoury to tackle COVID-19.”

He added that the UK government was “working at pace” with the NHS and clinicians to ensure Ronapreve is rolled out to NHS patients quickly.

MHRA interim chief quality and access officer Samantha Atkinson added: “Ronapreve is the first of its kind for the treatment of COVID-19, and after a meticulous assessment of the data by our expert scientists and clinicians, we are satisfied that this treatment is safe and effective. With no compromises on quality, safety and efficacy, the public can trust that the MHRA has conducted a robust and thorough assessment of all the available data.”

AstraZeneca has announced positive results from its PROVENT phase 3 trial that show that AZD7442, a combination of two long-acting antibodies, reduced the risk of developing symptomatic COVID-19 by 77% compared to placebo.

The trial studied more than 5,000 participants who did not have SARS-CoV-2 infection at baseline. During the trial, 25 people developed symptomatic disease including three cases of severe COVID-19 (including two deaths) in the placebo arm but there were no cases of severe disease or death in the treated cohort.

More than two-fifths of participants were 60 years and over and three-quarters had co-morbidities, which included conditions that can cause a reduced immune response to vaccination.

AZD7442 is the first antibody combination modified to provide long-lasting protection that has demonstrated efficacy in preventing COVID-19 in a clinical trial.

“The PROVENT data shows that one dose of AZD7442, delivered in a convenient intramuscular form, can quickly and effectively prevent symptomatic COVID-19,” said principal investigator and professor of paediatrics and medicine at the University of Colorado school of medicine, Myron Levin.

The ease of administration for AZ antibody combination has been highlighted. “This antibody combination treatment can be given via an intramuscular injection which makes it simpler to use in a community setting, as opposed to Ronapreve which is given via intravenous infusion,” commented Penny Ward, visiting professor in pharmaceutical medicine at King’s College, London.