Two weeks ago, I pointed out that half of 650,000 citizens aged 80+ years in England who had received 1st Pfizer/BioNTech dose before 4 January had received their 2nd before 25th January 2021. This “serendipity cohort” would need sophisticated analysis to deal with confounding (ie selection of those who received versus did not receive 2nd dose); and to cope with dramatically changing SARS-CoV-2 incidence and falling hospitalizations during January and February 2021. Today’s nation-wide analysis from Public Health England (PHE) includes, as co-author, the eminent biostatistician from Scotland, Chris Robertson, who led Scotland’s careful analysis of vaccine effectiveness (VE) at reducing COVID-19 hospitalizations but could not comment on VE after 2nd doses of the PfizerBioNTech vaccine because, in Scotland, so few were administered at 3 weeks after the 1st.

Today’s big reveal is that PHE’s analysis can and does focus on 2nd doses of Pfizer/BioNTech vaccine in England’s Serendipity Cohort of 80+ year olds who received their 1st Pfizer/BioNTech dose before 4 January, half of whom received their 2nd before 25th January 2021.

After adjustment, and relative to confirmed cases in days 4-9 after vaccination, VE for reducing confirmed COVID-19 cases peaked 70% (95% CI:  59% to 78%) at 28-34 days after 1st dose of Pfizer/BioNTech but was significantly higher at  87% (95% CI: 83% to 90%) at 7+ days after the 2nd dose.

Oddly, PHE fails to report results for England’s second “gifted” cohort, gifted by exercise of medical discretion. England’s second cohort comprises nearly 440,000 persons aged 18-79 years, mainly healthcare and social care workers, who received their 1st Pfizer/BioNTech dose prior to 4th January 2021, one quarter of whom received their 2nd dose before 25th January.  Being younger, the hospitalization rate and potentially also incidence of COVID-19 cases for this cohort will be lower so that PHE may be waiting for a further few weeks of follow-up before reporting. Indeed, the delay may be longer to allow commentary on how VE picks up after their delayed 2nd dose is administered  at 10-12 weeks after the 1st.

For 1st vaccinations of either type, virus-vectored DNA OxfordAstraZeneca or mRNA Pfizer/BioNTech,  administered on/after 4th January to persons aged 70+ years, the PHE team reports equal VE of 60% at 28-34 days after the 1st dose for reducing confirmed COVID-19 cases; 95% CI was 41% to 73% for OxAZ and 51% to 69% for Pfizer/BioNTech.

Excitingly, for both vaccines, and not demonstrated convincingly in randomized controlled trials because not powered to do so, the risk of hospitalization within 14 days of testing positive is reduced by 40% (95% CI: 33% to 52%, for Pfizer/BioNTech) for those who received their 1st dose  more than 14 days before their SARS-CoV-2 diagnosis date.

This preprint is again excellent news, particularly for those who received their 2nd Pfizer/BioNTech dose 3 to 4 weeks after their 1st dose.

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The preprint by Bernal and colleagues is the long awaited analysis of the effectiveness of the two vaccines currently being used in the UK. This is an effectiveness study and it is case control study of cases of infection against controls and a cohort study of hospitalisations and deaths. Case control studies are often used to determine the effectiveness of vaccines after release of vaccines for general use. Effectiveness studies such as this show the ability of the vaccine to reduce disease in the real world use, but because of the non-randomised study design such studies may be prone to some degree of bias. Nevertheless effectiveness studies are an essential approach to showing whether the vaccine is indeed as good as the phase 3 trials suggest.

The study by Bernal and colleagues is high quality and the authors undertook several analyses to understand potential biases. The authors also calculated adjusted odds ratios to account for differences in possible confounding variables. For hospitalisations, however, the authors calculated hazard ratios which are easier to understand as percentage reductions in risk. We can have confidence in the findings presented here. Indeed this is the probably the most reliable analysis of vaccine effectiveness yet published.

This study concentrates on people over 70 years and so provides one of the first good quality estimates of the effectiveness of the Oxford AstraZeneca vaccine in older people.  

The timing of the vaccine roll out campaign means that many of the people infected will have had the Kent variant, though very few would have had the South African or even Brazil variants.

The main findings are that a single dose of the Pfizer BNT162b2 vaccine is approximately 60-70% effective and a single dose of the Oxford AstraZeneca ChAdOx1 vaccine against symptomatic disease was approximately 60-75% at preventing symptomatic disease in adults aged 70 years and older in England. So it does look very much that there is not much difference in the value of the two vaccines in preventing disease in older recipients.  Two doses of the Pfizer BNT162b2 vaccine were approximately 85-90% effective, but too few people have had two doses of the Oxford AstraZeneca to draw conclusions about this vaccine.

Those vaccinated who went on to become a symptomatic case had a 44% lower risk of hospitalisation and a 51% lower risk of death compared to unvaccinated cases, though so far insufficient numbers of people have had the Oxford AstraZeneca vaccine to give very precise estimates.

So the main conclusions from this paper are that the two vaccines currently in use in the UK appear to be equally effective at preventing infection in older people. That both vaccines give about 2/3 protection in this age group though protection is somewhat greater after the second dose. Of perhaps even greater importance is that even if people still get a symptomatic infection they are still less likely to need to be admitted to hospital and less likely to die.

These results are hugely reassuring. Both vaccines are effective at preventing symptomatic disease in older people over 70 years old and at preventing hospitalisation and deaths in those who do get sick. This study gives very clear evidence that the UK strategy of delaying the second dose to allow more people to be protected by a first dose was the right approach to reduce the pressure on the NHS and reduce the number of deaths in this age group. This study provide strong reassurance that, as expected, the vaccine works well against the Kent variant. However, it is too early to judge how effective the vaccine will be against the South African, Bristol or Brazil variants.

These studies cannot be used to determine how effective either vaccine is at preventing asymptomatic infection or risk of being infectious to others so people should follow social distancing guidance in place irrespective of whether or not they have been vaccinated.

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These real world results from Public Health England demonstrate a very good effect from both vaccines after the first dose. The Covid vaccination strategy was designed to prevent as many deaths as quickly as possible. The bold decision to vaccinate more older people by delaying the second dose has undoubtedly saved a large number of lives.

These results provide the first robust data on the real-world effectiveness of the vaccine roll-out in the UK. The results demonstrate that a single dose of either the Pfizer/BioNTech or the Oxford/AstraZeneca vaccine provides a high level of protection against severe disease in the most vulnerable age-groups, with  approximately 80% protection against hospitalisations in the over 70 age-group. The data also show that both vaccines are reducing milder symptomatic infections in this age-group, with approximately 60% effectiveness 28 days after the first dose. This rises to close to 90% in those that received the second dose of the Pfizer vaccine. Recent research from Cambridge showed a similar effect on asymptomatic infections, and so it is likely that both vaccines will reduce transmission of the virus, supporting a cautious lifting of social restrictions in the coming weeks and months.

It is important to note that these results also demonstrate a very similar level of effectiveness between the two vaccines with no evidence of one working better than the other because the trends reported by the Secretary of State are based on too small numbers to be meaningful. All those that have been vaccinated to date should therefore feel reassured that they will be highly protected with one dose but will also further benefit from their second dose regardless of which vaccine they received.

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The data published tonight by Public Health England is very promising and is some of the first real-world data to emerge showing the effect of COVID-19 vaccines.  The central aim of all vaccination campaigns is to stop people getting seriously ill and save lives.  These new results, studying over 2 million people, show that both the Pfizer and Oxford/AstraZeneca vaccines are stopping people suffering symptoms from COVID disease and stopping them being hospitalised after one dose. The Pfizer COVID-19 vaccine also reduces the likelihood of dying from the disease. (It will take longer to get data on this measure on the Oxford/AstraZeneca vaccine as this vaccine was rolled out later.)

These findings are particularly welcome news due to the age range of the participants who were all aged 70 and over.  Previous clinical trials for both vaccines have not included many individuals from this age range. This is important because as we get older, our immune systems don’t function as well as they did when we were younger, meaning that older people sometimes produce lower immune responses to vaccination. The fact that vaccination is effective in significantly reducing symptomatic cases, hospitalisations and deaths from COVID-19 in this older age group is really positive news. Although more research is needed, this study also provides further reassurance around the UK’s decision to offer the two doses of the vaccine 12 weeks apart.

While this new data is encouraging, we still have much more that we need to understand about how effective these vaccines are against transmission and against some of the newer variants, along with needing a deeper immunological understanding of the components of immune memory generated. We look forward to seeing the detail of today’s welcome funding commitment for more research. While we can all take heart from the positive news on vaccine effectiveness in this study, we should not be complacent.  It is still critical that we all make sure we get two doses of the COVID vaccine within 12 weeks to ensure the best and longest lasting protection against disease.

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