A preprint, unpublished non-peer reviewed data, from the ComFluCOV study, looks at the safety and immunogenicity of concomitant administration of COVID-19 vaccines (Oxford-AstraZeneca or Pfizer-BioNTech) with seasonal influenza vaccines in adults.
This Roundup accompanied an SMC Briefing.
Prof Penny Ward, Independent Pharmaceutical Physician, Visiting Professor in Pharmaceutical Medicine at King’s College London, said:
“It’s not often that a publication is directly relevant to one’s own health decision making. Being a lady of mature years I have just received my invitation for the annual influenza vaccination, but the set date is a month or so prior to the earliest date I would be called for a COVID vaccine booster. What to do – wait and have them both together or take one then t’other? This paper is a timely report of the COMCOV study, which investigated the impact of giving an influenza vaccine at the same time as the second ChAdOx1 or BNT162b2 vaccine shot or giving an influenza vaccine 3-4 weeks after the second COVID vaccine shot. The primary assessment focused on reactogenicity of the two taken together or apart. No significant difference was observed regardless of whether the shots were given on the same day or 3-4 weeks separately. In addition, there was no major impact of co-administration on antibody response to either vaccine, indeed giving the two together might marginally increase response to the various components of the influenza vaccines. Although the point estimate of the response to the second COVID vaccine shot appeared slightly lower following concomitant administration of the quadrivalent influenza vaccines, as the ranges overlapped, this is unlikely to be clinically relevant. The study was not designed to investigate whether giving an influenza vaccine prior to a COVID booster would impact response to the latter, but, based on the results of this study, which is reassuring in respect of potential for interference, I think I can be confident that I can go ahead with my flu shot while waiting to be called up for the COVID vaccine booster. Thanks to the ComCov study team for getting this out into the public domain so I could answer my own question without needing to bother the local GP. Let’s get this out on the airwaves so other members of the public with the same dilemma can be similarly reassured.”
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 logistics of vaccinating a large proportion of the population against influenza and Covid-19 might be greatly simplified if the vaccines can be given simultaneously.
“There is a long history of vaccinating people against more than one disease simultaneously. This can most easily be done, for injectable vaccines, if the vaccines can be combined into a single injection; but until and unless such products become available (and a discussion of what would have to happen first can wait for another day), it is still much simpler, more convenient for the patient, and cheaper for healthcare providers if the vaccines can be given at the same time; “coadministered”.
“I cannot think of any examples where coadministration of vaccines is in any way unsafe (compared to administering them separately); and it is extremely unusual for coadministration to interfere with vaccine effectiveness. (It has happened, e.g. with Hib vaccines and other childhood vaccines, where one combination of vaccines was more effective than a combination of vaccines with different conjugate molecules.1 We understand why this happened with this particular combination, and similar issues do not apply to current flu and Covid-19 vaccines.)
“We would not expect any problems to arise from coadministration of flu and Covid-19 vaccines; but it is wise and precautionary to check for possible problems in clinical trials before authorising or recommending widespread coadministration. This study does just that.2
“I was curious about the claim, in the introduction, that “High rates of influenza, alongside further waves of COVID-19, are predicted for the coming Northern hemisphere winter, as there was little circulating influenza virus detected during the first wave of the COVID-19 pandemic[ref].” The reference cited does support the widely accepted idea that there has been little circulation of influenza during the Covid-19 pandemic, presumed to be due to the non-pharmaceutical interventions imposed to reduce transmission of Covid-19, and only to be expected given that Covid-19 is more transmissible than influenza. But no citation is given for the prediction of high rates of influenza. There certainly could be high rates of influenza in the coming winter; but in my opinion predictions remain speculative.
“It may also be the case that coadministration is not as necessary as we previously might have thought. We have already given a large proportion of the population two doses of Covid-19 vaccine, and by the time we gear up to being able to coadminister the two vaccines, it is not clear that we will need to vaccinate any more people against Covid-19. This might change in the future if it becomes apparent that further doses of Covid vaccines – boosters of current vaccines, or newer vaccines tailored to prevent variants as the SARS-CoV-2 vaccine mutates and evolves – would be beneficial. Depending on the duration of immunity, and the rate of evolution of new strains, regular, possibly annual Covid-19 vaccination (as with flu, for similar reasons) might be recommended; and then coadministration (better still a combined vaccine) might be very valuable.
“The research is complicated by the number of different possible vaccines, with two Covid-19 vaccines (AstraZeneca’s ChAdOx1 and Pfizer BioNTech’s BNT162b2) and three flu vaccines (Flucelvax QIV, Flublok Quadrivalent (QIVr), and Sequirus; Fluad, Adjuvanted Trivalent Influenza Vaccine) being considered. It appears to be of excellent quality.
“The immunological outcomes appear only to consider antibody levels and effectiveness: I did not find any mention or consideration of cellular immune responses or immune memory. This may be because it would take longer than has been available (for memory), and/or because measuring cellular responses is much harder to do. I note that the paper explicitly says that “Other immunological outcomes, which will be reported at a later date…These data were not available at the time of reporting.”
“With 126 participants per cohort the study is large enough to detect any common adverse consequences of coadministration, and – particularly given the low prior likelihood of interference – to justify wider authorisation of coadministration. It remains possible (although in my opinion highly unlikely) that population scale use of coadministration might identify very rare such effects.
“As you would expect following the administration of an active vaccine, some minor and transitory reactions occurred; but the level was acceptable and, as far as I can tell, little different to what would be expected after giving the two doses separately.
“Similarly, immune responses were not affected by coadministration.
Why are the doses given in opposite arms?
“So that researchers can tell which injection caused any local reactions. The same approach is generally used wherever two vaccines are given on the same day (although if only one limb is available doses can be given at least 2.5cm apart), so that it is easier to tell which vaccine caused any local reactions. NB: several of the vaccines given in infancy are given as more than one injection at the same appointment.
Does this suggest people should try and get their vaccines at the same time or simply that they shouldn’t worry if their appointments end up on the same day?
“People certainly shouldn’t worry if their appointments end up on the same day. Coadministration may be more convenient – only one trip to the GP surgery, clinic, or pharmacy as opposed to two. But apart from the convenience (and the cost to the NHS/providers), there is no medical or immunological reason to go out of your way to get the vaccines at the same time.”
‘The safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults: a phase IV, multicentre randomised controlled trial with blinding (ComFluCOV)’ is a preprint by Rajeka Lazarus et al.
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.
None others received