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expert reaction to preprint from Scotland looking at hospitalisations in Scotland and vaccinations

A preprint, an unpublished non-peer reviewed study, looks at effectiveness of the first dose of COVID-19 vaccines against hospital admissions in Scotland.

This Roundup accompanied an SMC Briefing.


Prof Sheila Bird, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge, said:

“Last week 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 by 24th January 2021.  This “serendipity cohort” would need sophisticated analysis to deal with confounding (i.e. 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 excellent nation-wide analysis by an eminent biostatistical and public health team from Scotland is just the sort of careful analysis that was called for: but without a focus on 2nd doses of Pfizer/BioNTech vaccine because their administration in Scotland was minimal.

“For Pfizer/BioNTech, vaccine effectiveness (VE) for reducing COVID-19 hospitalizations peaked at 28-34 days after Dose 1 at 85% (95% CI: 76 to 91); thereafter reduced to 66% (95% CI: 57 to 76) at 35+ days after Dose 1.  Coincidentally, this reduction is precisely the policy-relevant 20% reduction in VE for COVID-19 hospitalizations that the NIHR research-call is framed to detect by means of randomization to interval between 1st and 2nd doses.

“For the Oxford/AstraZeneca vaccine, which in Scotland was used predominantly in those aged 80+ years and available only since 4 January, VE at 28-34 days after Dose 1 for reducing COVID-19 hospitalizations was estimated at 94% (95% CI: 73 to 99).  The later start means that the current analysis cannot yet estimate Oxford/AstraZeneca’s VE at 35+ days after Dose 1.

“This preprint is excellent news!”


Prof Arne Akbar, President of the British Society for Immunology, said:

“The primary aim of all vaccination campaigns is to stop people getting seriously ill and save lives.  This initial data reported in this preprint on the effectiveness of one dose of a COVID-19 vaccine is extremely promising.  At 28-34 days after the first vaccine dose, hospitalisations were reduced by 85% in those who had received the Pfizer/BioNTech vaccine and by 94% in those that had received the Oxford/AstraZeneca vaccine.

“Although there does seem to be some difference in effectiveness levels measured across age groups, the reduction in hospitalisations for the older age groups is still impressively high.  We now need to understand how long lasting this protection is for one dose of the vaccine.  Although further research is needed, overall these new findings should provide reassurance around the UK’s decision to offer the two doses of the vaccine 12 weeks apart.

“While the results of this study indicate a good level of immunity after one dose, it is still the case that the highest and longest lasting protection from getting ill with COVID-19 will only be provided by getting two doses of the vaccine.  It is critical that all people eligible for COVID vaccination do return to get their second dose when asked to do so by their medical providers.”


Prof Sarah Gilbert, Professor of Vaccinology, University of Oxford, said:

“The real-world data from Scotland now provides evidence of high effectiveness of both the Oxford/AstraZeneca and BionTech/Pfizer vaccines in preventing hospitalisation in people over the age of 80, after a single dose, supporting our confidence in using this vaccine in adults of all ages.”


Dr Teresa Lambe, Associate Professor and Jenner Investigator, University of Oxford, said:

“When we first started this journey, we could only hope that a year later, real world data would show this level of impact from our vaccine against hospitalisation from severe illness.  It is a huge day for us all, especially the team who’ve worked so hard, and monumental in our battle against coronavirus.”


Prof Andrew Pollard, Professor of Paediatric Infection and Immunity, University of Oxford, and Chief Investigator on the Oxford vaccine trial, said:

“We are delighted to see that the real-world evidence reported today from the University of Edinburgh which confirms that both the Oxford-AstraZeneca vaccine and the Pfizer vaccine have a very substantial impact against hospitalisation with COVID19 disease.  Vaccines work.  We now need to make sure that everyone everywhere is protected.”


Prof Adam Finn, Professor of Paediatrics, University of Bristol, said:

“This study uses database linkage techniques to compare the risk of hospitalisation following a positive COVID-19 test or with a diagnosis of COVID-19 among the Scottish population and concludes that this risk falls progressively after receiving a single dose of either of the two currently available COVID-19 vaccines to a nadir after between 28 and 34 days.  The main strength is that it includes almost the entire population of the country and so is fully representative.  However, it is an observational study with the inherent risks of bias that always exist with such designs and, at the point in time of the data cut in mid-February, the relevant hospitalisation events that had occurred were not very numerous while the follow up period was still short, especially for the Astra-Zeneca vaccine which was deployed later.  For these reasons and because it is the first UK post-implementation study to report initial results publicly, the paper should be interpreted cautiously.  With those caveats, it is very encouraging to see these first signs that the immunisation programme is achieving its main objective of driving down hospitalisation rates.  Further results from this and other studies are awaited with great interest.”


Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“These are encouraging results from a well-conducted study.  However non-randomised (observational) studies of the effects of vaccines are subject, even in the best-designed and analysed studies, to potential biases making the results less certain than the statistical analysis suggests.  These biases can occur at the initiation of treatment, during follow-up and in the ascertainment of the outcome, resulting in the observed effect appearing larger or smaller than the true effect.

“This study is very useful in that it looks at hospitalisations, which are less subject to bias than getting a test result for presence of the virus, but there are other biases not only possible, but suggested in the results.  In the second week after vaccination there appears to be a notable benefit – 47% (95% confidence interval 39 to 53%).  This is most likely to be bias, particularly for the Oxford/AZ vaccine which from the randomised trial data may start to show efficacy later than the Pfizer vaccine.  A possible reason for this may be that those who are already unwell may not be able to be vaccinated but may still be hospitalised and that a “healthy vaccinee” effect can occur.  This makes for a biased assessment and uncertainty in the true effect that is not included in the statistical confidence interval.  The authors, in the press release “caution that the data does not allow for comparisons between the two [vaccines]” used in the study.

“There are other biases that can appear to diminish the estimate of benefit, such as those vaccinated having symptoms typical of vaccination (reactogenicity) that leads them to be tested for presence of SARS-CoV-2.  While this study does not use the test itself as an outcome, hospital admission within 28 days of a positive RT-PCR test is an outcome and so being vaccinated could lead to the admission being counted which may not occur if an unvaccinated person did not have a test.  In this study, such a bias is quite unlikely, but the point remains that various biases mean that results are more uncertain than may be realised.

“In spite of this, it is clear that these are definitely encouraging results looking at large numbers of hospitalisations.  The randomised trials had very few people with serious disease or hospitalisation, so this is helpful extra information.  However, it will be important that euphoria, especially from political sources that do not understand the uncertainty in the numerical values, does not cause premature decisions to be made.  Cautious optimism is justified.

“The data available in Scotland through the Rapid Preliminary Inpatient Data (RAPID) system enables data at the time of admission to be recorded.  This is not generally true in England where data on admission tends to become available only at the end of a period of admission when diagnoses are available.  Overall, this study is a great achievement with analysis being done at a national level utilising the structure of the NHS and linking multiple sources of data to answer vital questions in relation to this pandemic.”


Prof Anthony Harnden, Deputy Chair of Joint Committee on Vaccination and Immunisation, said:

“This study from Scotland shows good evidence that three weeks after a single dose of either the Pfizer – BioNTech or Oxford Astra Zeneca vaccine the risk of hospital admission due to Covid-19 is substantially reduced across all age groups.”



Preprint (not a paper): ‘Effectiveness of first dose of COVID-19 vaccines against hospital admissions in Scotland: national prospective cohort study of 5.4 million people’ by Dr Eleftheria Vasileiou et al.  This work is not peer-reviewed.



All our previous output on this subject can be seen at this weblink:



Declared interests

Prof Sheila Bird: “SMB is Honorary Professor at Edinburgh University’s College of Medicine and Veterinary Medicine and, until recently, Visiting Professor at Strathclyde University’s Department of Mathematics and Statistics but took no part in the analyses reported from Scotland.”

Prof Sarah Gilbert: “Sarah Gilbert is Professor of Vaccinology at Oxford University, and was co-founder of Vaccitech.  She has received research funding for coronavirus vaccine research from EPSRC, UKRI, CEPI and NIHR.  Oxford University has entered into a partnership with Astra Zeneca for the development of a coronavirus vaccine.”

Dr Teresa Lambe: “Teresa Lambe is an Associate Professor at the University of Oxford, she has previously done limited consultancy work and has received research funding for coronavirus vaccine research from UKRI.  Oxford University has entered into a partnership with Astra Zeneca for the development of a coronavirus vaccine.”

Prof Andrew Pollard: “Andrew Pollard is chair of the UK Department of Health and Social Care’s (DHSC) Joint Committee on Vaccination and Immunisation (JCVI), but does not chair or participate in the JCVI coronavirus committee, and is a member of the World Health Organization’s (WHO) Strategic Advisory Group of Experts.  He has received research funding for coronavirus vaccine research from UKRI, CEPI and NIHR.  Oxford University has entered into a partnership with Astra Zeneca for the development of a coronavirus vaccine.”

Prof Arne Akbar: “Receives funding form the Medical Research Council, The Leo Skin Foundation (Denmark), The British Skin Foundation and Dermatrust.”

Prof Adam Finn: “AF is chief investigator on another study currently investigating COVID-19 vaccine effectiveness using a different methodology.”

Prof Stephen Evans: “No conflicts of interest.  I am funded (one day per week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them.  I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI.  I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs.  I am a participant in the Oxford/Astra Zeneca trial, and on 13th January 2021 learnt I had received the active vaccine.”

None others received.

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