Delaying the second dose of covid-19 vaccines
BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n710 (Published 18 March 2021) Cite this as: BMJ 2021;372:n710Read our latest coverage of the coronavirus outbreak
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Dear Editor,
The UK the Joint Committee on Vaccination and Immunisation (JCVI) has issued advice [1] that “initially vaccinating a greater number of people with a single dose will prevent more deaths and hospitalisations than vaccinating a smaller number of people with 2 doses”.
This utilitarian strategy to vaccinate where vaccination can do the greatest good, as quantified by the reduction of deaths and hospitalisations, can hardly be challenged, indeed the Secretary for State, Matt Hancock has said that it saving lives is the government’s strategy. However, the decision to delay a second dose for some people has been questioned [2] and concerns remain about effectiveness in older adults. [3] There has been particular concern regarding the Pfizer-BioNTech vaccine because no variation in dosage regime was tested in its clinical trial. [4]
The optimal timing for giving a second dose of the Pfizer vaccine has yet to be established by clinical trials. If delaying the second dose is of benefit, then clearly that should be done. However, if there is a conflict of interest between those waiting for a second dose and younger groups waiting for a first dose, then the relative balance of risks would seem to be a fair way to set priorities.
The JCVI estimates [5] of the efficacy of the Pfizer vaccine are “89% from first dose; 95% from two doses”. This means that the second dose is estimated to save from covid only 6.7% the number that a first dose would save. This can be thought of as a diminished return. The first dose of the Pfizer vaccine gives much more of a benefit than the second with regard to immune protection.
Balanced against the diminished return of repeat vaccination of the same person, there are diminishing returns experienced in giving a first dose to younger and younger age groups. The ONS covid mortality statistics [6] for the week ending 15 May 2020 (towards the end of the first wave of covid deaths in the UK) show that from the age of around 40 to over 90 the risk of dying from covid approximately doubles with every five years of increased age. So, someone 10 years older has 4 times the covid mortality risk; 15 years older, 8 times; 20 years older, 16 times; and so on.
For age differences of 15 years or less there is more likely benefit to giving a younger person a first vaccination than giving an older person a second. (8 x 6.7% is less than 100 %) Although the older age group has 15 times the mortality, a second vaccination gives only 6.7% of the benefit of the first. So there is more benefit to rolling out first doses to the younger group. However, for an age difference of 20 years or more the increased relative risk of being older so great that there is more benefit to giving a second vaccination to the older age group. (16 x 6.7 % is more than 100 % ).
Following the JCVI strategy of starting vaccination where most lives are likely to be saved, groups should be vaccinated in the order of decreasing risk. Age groups could be prioritised according to their relative covid mortality risk with first vaccinations interspersed with second doses of older ages. Following the above criteria, a particular age group would not receive a second vaccination until those up to 15 years younger (but not those 20 years younger) have been offered a first vaccination, leading to the following order of priority.
Order of priority for the rollout of the Pfizer vaccine :
90+ jab 1, 85+ jab 1, 80+ jab 1, 75+ jab 1, 90+ jab 2, 70+ jab 1, 85+ jab 2, 65+ jab 1, 80+ jab 2, 60+ jab 1, 75+ jab 2, 55+ jab 1, 70+ jab 2, 50+ jab 1 etc.
As an example, someone over 90 years of age is so vulnerable to COVID-19 that a dose of vaccine would be more likely to save the life of the 90-year-old than the life of a seventy-year-old offered it as a first dose. Nevertheless, in the UK second doses are only available three months after the first, irrespective of vulnerability.
Those at particular risk due to, for instance, working the covid front line, or those with underlying medical vulnerabilities, could be vaccinated alongside whatever older age group is at equivalent risk.
This general method of prioritisation could be applied outside the United Kingdom using the national statistics of other countries. Local factors might conceivably affect the relative risks from covid of different age groups, although so far it seems universally true that the risk is higher for older people.
As more and better data become available it may be possible to use vaccine efficacy calculated from the number of covid fatalities rather than the number of cases. There will be more precise statistics describing the variation of covid mortality according to age. (Here the rough approximation is use of simply doubling risk for every five years of additional age.) The relative benefit of having a second dose of vaccine may be determined more accurately than the figures used by the JCVI. These considerations may suggest alterations to the priority order for vaccinations. However, whatever improvements are made, some sort of quantitative assessment of the relative risks of different groups seems necessary.
References
[1] Prioritising the first COVID-19 vaccine dose: JCVI statement UK Gov Dept of Health and Social Care Jan. 2021
[2] BMJ 2021;372:n18
[3] BMJ 2021;372:n710
[4] Polack FP, Thomas SJ, Kitchin N, et al., C4591001 Clinical Trial Group Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N Engl J Med2020;383:2603-15. doi:10.1056/NEJMoa2034577. pmid:33301246
[5] https://assets.publishing.service.gov.uk/government/uploads/system/uploa...
[6] https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarri...
Competing interests: No competing interests
Cuba will complete in August all the doses necessary to vaccinate its population against COVID-19.
Dear Editor
Cuba expects to complete the necessary doses of its most advanced vaccine candidates in August to immunize the entire population against COVID-19.
The island could be the first country to immunize its entire population with its own vaccine. Both Abdala and Soberana 02 have their production systems.
It was designed this way so that they did not compete, so many vaccines could be manufactured in a short period of time.
During the last weeks, the processes of scaling up the production of both vaccines have been carried out and at the moment are already at an industrial level.
In the case of Abdala, it is specified that the Center for Genetic Engineering and Biotechnology (CIGB) participates in its production system, where the antigen is manufactured, and then it is formulated in the Aica Laboratories. Meanwhile, the Soberana 02 Center involves the Molecular Immunology Center, which manufactures the RBD antigen; the Finlay Institute, which conjugates this antigen with tetanus toxoid, and the final vaccine, the formulation of this conjugated antigen, is carried out at the National Center for Biopreparations (Biocen). BioCubaFarma has designed an operations plan until December, which defines the number of doses that will come out month by month of each of the vaccines, which will increase over time.
We are increasingly reaching industrial stability, we have batches of vaccines manufactured to begin the health intervention, which passed a rigorous evaluation process, Cuba has an experience of more than 30 years in the development and production of vaccines, which have been employed in more than 30 countries.
Kind Regards
Competing interests: No competing interests