This important study adds to the body of evidence that supports the view that single dose vaccination has been highly effective at reducing severe disease due to the SARS CoV2 virus in the UK elderly.  In comparison to the large PHE study reported on 1st March, the Bristol study is smaller but more detailed. This trade-off is helpful since overall conclusions are more robust if consistent results are obtained from different study designs and datasets.

The Bristol case-control study has collected data from every adult patient admitted to two Bristol NHS hospitals with evidence of acute lung disease.  In total there were 136 cases and 298 controls from 18th December 2020 to 26th February 2021, and for each patient it was determined whether they had been vaccinated, and with which vaccine, and whether they were infected with SARS CoV2 (case) or not (control).  Adults must have been eligible for vaccination (i.e. aged at least  80 years by end March 2021).   Like the PHE study, and other recent studies, it is observational in design and there remains potential for bias.  However the consistency of the results with other studies is quite remarkable. The authors draw sensible conclusions and carefully analyze the data in weekly intervals to account for anticipated time trends in infection prevalence, vaccine prioritization, etc.  Account has also been taken of other known confounders, such as social deprivation and sex.  As expected, more case-control data are available for the Pfizer/BioNTech vaccine (404 patients) than for the Oxford/AstraZeneca vaccine (126 patients), and the latter had more patients sent from care homes due to the timing of the respective vaccine roll-outs.

From separate analyses, the Vaccine Effectiveness (VE) was 71.4% (95% confidence interval 46.5, 90.6) for Pfizer/BioNTech and 80.4% (95% CI 36.4, 94.5) for Oxford/AstraZeneca, although when a like-for-like time period was used for the Pfizer/BioNTech vaccine, VE increased to 79.3% (95% CI 47.0, 92.5).  All in all, impressive results for both vaccines.

There is now overwhelming evidence that single dose vaccination has been highly effective in the short-term to reduce severe COVID-19 disease, regardless of the approved vaccine administered.  The optimal approach to developing long-term immunity to SARS CoV2 and its variants is still to be determined, although a randomised trial is underway in the UK to explore the varying immunological response to different dosing intervals and different vaccine combinations.

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Observational studies of vaccine effectiveness are never simple to undertake, analyse and interpret. Most recent studies have relied on information in population-based databases with linkage to vaccination and outcome data. Traditionally many studies were done using a particular form of case-control study called a ‘test-negative design’ which can be done using a database but may also be carried out using prospective data collection, especially in a hospital setting. The AvonCAP study is an example of such a study. It is useful to have a variety of studies which can have different biases so that an overall picture of vaccine effectiveness does not rely on similar designs which may have similar biases.

This study is a very useful addition to the surveillance of effectiveness of vaccines, and although not nationally based provides reasonably reliable answers.

The exact estimates of effectiveness should not be the headline, since there is considerable uncertainty in the exact value related to the numbers of patients in the study, but also due to the possibility of inevitable biases in any observational study. What is clear is that these results provide further evidence that the vaccines are effective both in an older age-group less studied in the trials and for an outcome which was rarer in the trials than in ‘real-world’ use, namely hospitalisations.

There is a particular bias that this design avoids that is related to patients seeking healthcare differently when they have been vaccinated. This study looks at all those being hospitalised for acute respiratory disease and examines the vaccination status of those who test negative for the presence of the SARS CoV-2 virus.

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This is a well-conducted case control study looking at the impact of vaccination on older populations in the south-west of the UK. Different study types can be used to look at vaccine effectiveness. A clinical trial involves prospective recruitment of participants who are then administered a vaccine or placebo. A case control study looks back at ‘what has already happened’, so is an appropriate method for examining ‘real-world’ data. This study covered patients admitted to hospital, aged >80, and with a diagnosis of respiratory disease. The cases had a positive test for COVID-19, the controls had a negative test. The researchers then assessed levels of vaccination between the two groups.

One of the key aims of the vaccination roll-out is to reduce hospitalisation and death from COVID-19 in vulnerable populations, since this has posed a massive burden on the NHS over much of the last 12 months.

This case control study estimates high levels of protection in older populations after one dose of either the Pfizer or Oxford vaccine. There are limitations, such as the wide confidence intervals around both the Pfizer and Oxford AstraZeneca data, indicating uncertainty as to the true level of protection given by the vaccine. However, the results here are underpinned by similar findings from the emerging body of evidence that covers clinical trials and analyses of real-world data.

Overall, this looks like further good news around COVID-19 vaccines. There has been a very high uptake so far in priority groups. The excellent effectiveness should result in fewer COVID-19 admissions and thus an easing of the huge pressures on the NHS over the coming months. The key beyond this will be to ensure high uptake in younger populations. This is important for various reasons, including to lower the incidence of long COVID that can occur with mild infection, to reduce onward transmission to susceptible individuals who haven’t got full protection, and to reduce the risks of new variants emerging that may lower the impact of vaccine effectiveness.

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This latest paper by Hyams and colleagues from Bristol is a test-negative case-control study of hospitalised patients with respiratory disease. In essence they compare patients admitted with respiratory symptoms with a positive COVID test against those  patients admitted with respiratory symptoms who then test negative for COVID. This study design (sometimes known as a case-case study) is a well established design and has the benefit of relatively easy recruitment of the control group which these days can often pose great difficulties. This type of study design is not without its problems, however. The main issue is that because the control group also has a disease any risk factors for that disease could appear to give significant negative associations with the outcome of interest. However, given that it is unlikely that immunization would affect the risk of non-COVID disease this is not likely to have had an important impact here. The other issue is that false negative tests would lead to incorrect allocation of cases to the control group and so reduce the apparent effectiveness of vaccine but again these are likely to represent only a small proportion of cases.

In any event, this study provides important additional evidence that both the Oxford AstraZeneca and the Pfizer vaccine are both highly effective at keeping people out of hospital and so presumably keeping people alive. As with the recent pre-print from Public Health England Oxford AstraZeneca vaccine seems to perform marginally better than the Pfizer vaccine at keeping people out of hospital although much of the apparent benefit of Oxford over Pfizer seems to be because of the fact that Pfizer was being used earlier and when analyses were restricted to the same weeks when both vaccines were being used much of this apparent benefit was reduced.

So the main conclusion from this study is that a single dose of either the Oxford AstraZeneca or the Pfizer vaccine are both roughly equally effective at keeping elderly and frail people out of hospital and so reducing risk of death. Furthermore the balance of evidence is very strongly that both vaccines are roughly equally effective with the Oxford AstraZeneca maybe having a slight edge (though we will have to wait for much more date to know that for certain).

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