A study published in the Lancet looks at effectiveness of the Pfizer-BioNTech COVID-19 vaccine up to 6 months in a large integrated health system in the USA.
Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, Immediate past Chair of the BMA Public Health Medicine Committee, said:
“The English government has put a huge amount of faith in the Covid-19 vaccines as our way out of the coronavirus pandemic, yet there remain a number of unknowns about the vaccines.
“When the coronavirus pandemic first became apparent, we didn’t know if we would be able to produce a vaccine against a coronavirus, let alone how effective such vaccines might be.1 One of the “known unknowns” was how long any immunity would last. There were concerns, based on what we knew of coronavirus infections in humans, that immunity might be of short duration – maybe a couple of years, perhaps even less.
“We have since discovered that vaccines are more effective than we had dared hope; but, of course, it takes time to observe how long this efficacy will persist, and this paper helps us to understand this, at least for one of the vaccines.
“As with other aspects of vaccine effectiveness, we need to be clear about what we are looking for. We know that vaccines in general – and Covid-19 vaccines in particular – are most effective at preventing severe disease, and least effective at preventing mild (but potentially infectious) disease. With Covid-19 we might also want to consider effectiveness at preventing “Long Covid”.
“The importance of each differs. Effectiveness against severe disease reduces hospital admissions and deaths, but if the vaccine is ineffective against minor disease and infectiousness, it will have little effect on the extent to which the vaccine circulates in the community, whereas greater effectiveness against any infection will limit spread from people who have been vaccinated, and thus decrease the effective R number (Re).
“We also need to know if the existing vaccines continue to remain effective as the virus mutates and evolves, producing new strains or variants.
“This paper helps us to understand the effectiveness of one of the Covid-19 vaccines (Pfizer BioNTech’s mRNA BNT 162b2 vaccine).2 The press release is an accurate description of the paper.
“The paper describes an observational study, using record linkage to look in people’s medical records for evidence of Covid-19 vaccination or infection, and the two outcomes:
“It was then able to compare the rates of these outcomes between people who had, and who had not been partially or completely vaccinated with the BNT 162b2 vaccine.
“The study population was large – nearly 5 million individuals before exclusions, nearly 3.5 million analysed; and the population involved is one in which the delta variant became prevalent. The analysis appears to have been robust. There were about 185,000 Covid-19 infections, and over 12,000 hospital admissions. These are large numbers, so the study had high statistical power, including enough outcomes to do subgroup analyses to look at other risk factors such as race and coexisting medical conditions. Such data will inform decisions about whether additional doses may be required, and who stands to benefit most from (and should thus be prioritised for) such doses.
“A proportion of the positive PCR test results were further analysed to identify which Covid-19 variant was involved.
“Other studies have looked at antibody levels in vaccine recipients, and showed that they drop over time, so some waning of efficacy is to be expected. But once the immune system is “primed”, people can be expected to have immune memory, so that the immune system can respond very rapidly to an antigen it recognises as foreign so that, if infected, they can attack the virus before it can cause serious disease; or even, before it causes any symptoms. So one might expect a decline in effectiveness against infection (as preventing infection requires higher levels of circulating antibodies), while continuing to protect against severe illness.
“This is precisely what this paper found. The headline figures show that, for any infection:
“Vaccine effectiveness against infection for the fully vaccinated decreased with increasing time since vaccination, declining from 88% (95% CI 86–89) during the first month after full vaccination to 47% (43–51) after 5 months”
(NB – “after 5 months” refers to events occurring during the fifth month; six months is at the end of the fifth month, so the study does show what happens in the six months after vaccination.)
“The study was also able to compare effectiveness rates according to the variant of the virus that had caused the disease. We should, again, be reassured that effectiveness against the delta variant does not fall off any more quickly than it does with other variants.
“For hospitalisation, the headline figures show:
“Among fully vaccinated individuals of all ages, overall adjusted vaccine effectiveness estimates for COVID-19 hospital admissions were 87% (95% CI 82–91) within 1 month after being fully vaccinated, and 88% (82–92) at 5 months after full vaccination, showing no significant waning.”
“This is as we would expect; and it is very reassuring to see that vaccine effectiveness against hospital admission is maintained throughout this time.
“As the authors say in the discussion:
“Our findings underscore the importance of monitoring vaccine effectiveness over time and suggest that booster doses might eventually be needed to restore the high levels of protection observed early in the vaccination programme.”
“Given the vaccine’s continuing effectiveness against severe disease over the course of this study, this would apply particularly to the vaccine’s ability to prevent infection and thus onward transmission.”
Prof Penny Ward, Independent Pharmaceutical Physician, Visiting Professor in Pharmaceutical Medicine at King’s College London, said:
“This publication describes real world evidence from the USA on the effectiveness of the Pfizer BioNtech vaccine assessed using data from a large healthcare database from the Kaiser Permanente organisation. The data align with information from the UK with effectiveness against infection declining over time but effectiveness in preventing hospitalisations being sustained. Because the organisation sequenced all cases with a positive PCR test, the authors were also able to consider the impact of different variants on vaccine effectiveness. The information suggested that reduced protection from infection was similar regardless of the variant identified and therefore that declining effectiveness is a result of waning vaccine effect affecting all strains in circulation rather than a variant insensitive to the vaccine. The results also demonstrate potential for more rapid decline in protection among the elderly population (>65 years) who are also at most risk from incident disease. Interestingly children aged 12-15 had more sustained protection at month 3-4 than older teenagers and adults, which may reflect the greater antibody level noted in clinical trials in this age group and potentially suggest more sustained protection might be seen in vaccinated younger teenagers – it will be interesting to see if this is confirmed as observation continues. The data are consistent with the reported results from the initial efficacy trial in which reduced protection against illness was noted 6 months after the primary course. In general, if the objective of vaccination is to prevent illness and prevent continued spread of infection, the information suggests need for boosters 6 months after completion of the first vaccine course, particularly among the most vulnerable, in whom infection may lead to more severe illness and death. This approach has already been adopted in the UK where the booster campaign is now underway.”
‘Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study’ by Sara Y Tartof et al. was published in The Lancet at 23:30 UK time on Monday 4 October.
All our previous output on this subject can be seen at this weblink:
Dr Peter English: “Dr English is on the editorial board of Vaccines Today: an unpaid, voluntary, position. While he is also a member of the BMA’s Public Health Medicine Committee, this comment is made in a personal capacity. Dr English sometimes receives honoraria for acting as a consultant to various vaccine manufacturers, most recently to Seqirus.”
Dr Penny Ward: “No COIs. I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development. Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases. Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody). These are my personal views and do not reflect those of either institution.”
None others received.