February 19, 2021

expert reaction to Correspondence article on data from Israel on infections in healthcare workers after first dose of Pfizer-BioNTech vaccine

A letter published in the Lancet looks at data from Israel on SARS-CoV-2 infections in healthcare workers after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine.

Dr Peter English, Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“This is good news.  It supports earlier data suggesting that, from 6 weeks or so after vaccination, vaccine efficacy is likely to be at least 85% – possibly considerably better – at least in vaccine recipients of working age.

“This is a letter, rather than a research paper – as such the data are quite limited, and I would expect far more details to be published in due course.  The letter describes the outcomes of identifying 9109 healthcare workers (these individuals comprise the ‘study cohort’) as eligible for vaccination.  A vaccination programme, in which the vaccine was offered to these individuals, started on 19 December 2020 (the start of the study period).  The data presented were collected up to 24 Jan 2021 (the end of the study period for this particular study – no doubt the surveillance will continue).

“The vaccination programme coincided with a third wave of Covid-19 cases, which peaked during the study period, meaning that a large number of the healthcare workers were exposed to the virus, and some of them became infected.

“The study followed up all of the cohort, and any who developed symptoms were tested for Covid-19.  Some appear to have been tested without having had symptoms, but there was no ‘active laboratory surveillance’, meaning that the cohort were not all tested routinely – certainly not frequently enough to be confident of detecting cases (and we should also bear in mind that the best tests available – PCR tests – still miss up to 30% of true positive cases).  Careful records were maintained of when staff members were vaccinated, so they knew how long after vaccination people became unwell (and not all staff were vaccinated during this period).

“The programme involved giving the second dose of vaccine at 21 or 22 days after the first dose.

“By the end of the study period, 7214 (79% of the 9109 eligible staff had received the first dose of vaccine, and 6037 (66%) had received their second dose.  During the study period there were 170 SARS-CoV-2 infections (Covid-19 cases, which could include asymptomatic cases) in the study cohort.  Of these, 89 (52%) were unvaccinated, 78 (46%) had received a single dose of vaccine, and three (2%) had received two doses of vaccine.

“Attempts were made to identify the source of the infection (within the hospital setting or ‘nosocomial’, or in the community, i.e. outside the hospital).  “There were no nosocomial clusters” means that there were no groups of people possibly infected by the same source within the hospital.

“The authors compared the rates of SARS-CoV-2 infection in the people who had been vaccinated with those who had not been vaccinated.  It also looked at the number of doses they had received and, crucially, the time between vaccination and the onset of infection.  This is important because it appears to take up to 3 weeks for full protection from the first dose.

“They found that in the first 14 days after vaccination, vaccinated people were 44% less likely to become infected, compared to unvaccinated people – the rate of infection was half what you would have expected had they not been vaccinated.  As you would expect, given that vaccine efficacy increases over time, on days 15-28 after the first dose, protection was considerably greater, at 75% protection.

“Cases were also compared with the communities they were in, and the proportion you would have expected to have become infected was adjusted for this; after doing this the protection appears even better, at 47% and 85% in the 1-14 and 25-28 day periods respectively.  The authors will, no doubt, explain more clearly the methods of adjustment – it is not very clear from this short letter how this was done.  Until we see the methods we need to remain a little cautious about it (although I strongly suspect the authors will be able to explain and justify their methods).

“As far as I can tell, this particular letter does not include data on severe and mild infection – from other evidence (and experience with vaccination more generally) we would expect the vaccination to be more protective against severe disease than against mild disease, and more protective against mild disease than against asymptomatic infection.  We may see more information on this when a more complete publication is made available.  As the authors acknowledge, the lack of ‘active laboratory surveillance’ means that they are likely to have missed some asymptomatic cases.

“From what we can see from this letter, this appears to have been a rigorously conducted, real-world study of the effects of vaccination.

“I expect that, when the full study is published, we will see more data aimed at ruling out potential biases.  For example, were those vaccinated earlier systematically different from those vaccinated later?

“Other evidence suggests that the efficacy of vaccination will continue to improve well after the (in this case) three weeks at which the second dose is given, so these data support earlier data suggesting that after 6 weeks or so, vaccine efficacy against symptomatic disease is likely to be of the order of 90%, possibly higher.”

Prof Deborah Dunn-Walters, Chair of the British Society for Immunology COVID-19 and Immunology Taskforce and Professor of Immunology at the University of Surrey, said:

“Due to the high percentage of the Israeli population vaccinated so far, we have been awaiting data from there to indicate the first signs of how effective COVID-19 vaccines are outside of a clinical trial setting and how dosing schedule plays into this.  These data on a good sample size of over 9,000 people show that the Pfizer/BioNTech vaccine is 85% effective in stopping symptomatic disease at 15-28 days after the first dose.  This is certainly promising.

“The timescale over which effectiveness is measured in this study (at 15-28 days) is important.  The immune response generated by any vaccine takes approximately 10-14 days to develop the all-important immune memory that stops us getting sick if we come in contact with the real virus.  Studies that look at infection rates from 0-14 days after the first dose of a vaccine are not very informative as we know that the immune system is building its memory at this time and protection will not yet be up to maximum power.

“It should be noted that this study was carried out on people of working age, so it will be informative to see a similar study in older people after one dose.  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 show that a good level of immunity is present after one dose of the Pfizer/BioNTech vaccine, 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.”

‘Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 vaccine recipients’ by Sharon Amit et al. was published in the Lancet on Thursday 18 February 2021.

DOI: 10.1016/S0140-6736

Declared interests

Dr Peter English: “No interests to declare.”

Prof Deborah Dunn-Walters: “No interests to declare.”