Covid-19: Two rare vaccine side effects detected in large global study
BMJ 2024; 384 doi: https://doi.org/10.1136/bmj.q488 (Published 26 February 2024) Cite this as: BMJ 2024;384:q488
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Dear Editor
The documentation of an unequivocal causal link between two life-changing side effects(vaccine-induced thrombosis with thrombocytopenia, and Guillain-Barre syndrome) and the use of the Astra Zeneca vaccine[1] is a reinforcement of a fundamental principle of clinical practice which either the Joint Committee on Vaccination and Immunisation(JCVI) or the Medicines and Healthcare products Regulatory Agency(MHRA) failed to grasp during the entire tenure of their participation in the UK vaccination programme.
When "alarm bells" started to ring [2], both the JCV! and the MHRA failed to grasp the principle that the crucial issue was the choice between a vaccine with a favourable benefit/risk profile(Vaccine A) versus a vaccine with an unfavourable benefit/risk profile(Vaccine B), notwithstanding the fact that both Vaccine A and Vaccine B could prevent millions of COVID-19-related deaths. This principle can be captured in a formula in which the parameters comprise "number needed to vaccinate" in order to prevent one COVID-19-related death and number needed to vaccinate to trigger the occurrence of one life-changing vaccine-related side effect. If Vaccine B were shown to be responsible for a fatal side effect that might have been averted through the substitution of Vaccine A for Vaccine B, then even 80 deaths which could have been averted by that strategy would be 80 deaths too many.
In the UK context the Pfizer vaccine belonged to the Vaccine A category, given the fact that it was characterised by the benefit of a 95% efficacy[3], countered by a modest risk of vaccine-related myocarditis, the latter associated with 2 deaths among 192, 405, 448 vaccinated individuals during the period 14 December 2020 to 31 August 2021)[4]. The AstraZeneca vaccine, characterised by 62.1% efficacy in 8,895 subjects tested with the 2 full doses subsequently used in clinical practice[5], and 74% efficacy in a subsequent trial[6] , belonged to the Vaccine B category, given the fact that as far back as October 2022 an International Network cohort study showed that , compared with the Pfizer vaccine, the AstraZeneca vaccine was associated with a greater likelihood of vaccine-related venous thrombosis with thrombocytopenia[2]. The syndrome of Vaccine induced thrombosis with thrombocytopenia(VITT) had, by then, claimed 80 UK lives[7].
Given the fact that prospective vaccinees were never offered a choice between Vaccine A and Vaccine B, future vaccination campaigns could make amends by offering prospective vaccinees a choice between the "free" vaccine offered by the NHS(ie free at the point of delivery) and any other vaccine available in the private sector. The benefit/risk profiles of all available vaccines should be widely publicised.
Although that strategy would reinforce health inequalities, an analogy analogy already exists in the proposed strategy for "booster jabs could go on sale privately in UK in 2024"[8].
I have no conflict of interest
References
[1]Faksova K., Walsh D., Jiang Y et al
COVID-19 vaccines and adverse events of special interest
A multinational Global Vaccine Data Network(GVDN) cohort study of 99 million vaccinated individuals
Vaccine
https://doi.org/10.1016/j.vaccine.2024.01.100
[2] Li X., Burn E., Duarte-Salles 7 et al
Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events with different covid-19 vaccines: International Network cohort study from five European Countries and the US
BMJ 2022 ;379:e071594
[3]Polack FP., Thomas SJ., Kitchin N et al
Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine
N Engl J Med 2020;383:2603-2615
[4[ Oster ME., Shay DK., Su JR et al
Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021
JAMA 2022;32:331-340
[5]Voysey M., Clemens SAC., Mahdi SA et al
Safety and efficacy of th ChAd Ox1 nCoV-19 vaccine(AZD 1222) against SARS-CoV-2 an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Lancet 2021;397:99-111
[6] Falsey AR., Sobieszczyk ME., Hirsch S et al
Phase 3 safety and efficacy of AZD1222(ChAd Ox1 nCoV-19) Covid-19 vaccine
N Engl J Med 29 September 2021
DOI:10.1056/NEJM oa 2105290
[7]GOV.UK
Coronavirus vaccine summary of Yellow card reporting
Updated 24 June 2022
https://www.gov.uk
[8[Badshay N
Covid booster jabs could go on sale in UK in 2024
Guardian 18 august 2023
Competing interests: No competing interests
Re: Covid-19: Two rare vaccine side effects detected in large global study. A cautionary tale with wider implicationsThe
Dear Editor
The causal link between vaccination practice and vaccine-related side effects [1],[2], has wider implications which need to be explored also in the context of the relationship between vaccination practice and the emergence of variants of concern.
At the time that Li et al went to press (October 2022), there were already 1,195,626 recipients of the second dose of the AstraZeneca vaccine in the UK, 307,344 in Spain, 31,200 in Germany, 15,067 in France, and 38,884 in the Netherlands. By that date, recipients of the second dose of Pfizer vaccine numbered 1,369,238 in the UK, 1,357,509 in Spain, and 321,099 in Germany [1].
By the 3rd February 2023, 24 million second doses of AstraZeneca vaccine and 25 million second doses of Pfizer vaccine had been administered in the UK [3].
However, despite the intensity of the UK vaccination campaign, by the 20th June 2022 there were 276,337 cases of the Alpha variant in the UK, much higher than in Germany (104,282 cases), France (35,745 cases), Spain 925,194 cases), Netherlands (30,334 cases), and only marginally higher than in the USA (249,812 cases) [4].
Also by that date there were 1,159, 560 cases of the Delta variant in the UK, many more than in Germany (208,103 cases), France (141,470 cases), Spain( 47,328 cases), Netherlands (45,782 cases), and only marginally fewer than in the USA (1,492,049 cases) [5].
Finally, by the 4th July 2022, there were 1,216,717 cases of the Omicron variant in the UK, many more than in Germany (331,453 cases), France (146, 140 cases), Spain (45,846 cases), and Netherlands (35,558 cases)[6].
Did this consistent pattern signify that the difference in vaccination practice between the UK and Europe (choice of vaccine and extension of the interval between the first dose and the second dose) might have put the UK at a serious disadvantage?
These are issues worthy of scientific scrutiny.
I have no conflict of interest.
References
[1]Li X., Burn E., Duarte-Salles et al. Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different COVID-19 vaccines: international network cohort study from five European countries and the US. BMJ 2022;379:e071594
[2] Faksova K., Walsh D., Jiang Y et al. COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network(GVDN) cohort study of 99 million vaccinated individuals
Vaccine https://doi.org/10.1016/j.vaccine.2024.01.100
[3] GOV.UK. ARCHIVED Coronavirus vaccine summary of Yellow Card Reporting. Updated 3rd February 2023
[4] John Elflein. Number of SARS-CoV-2 Alpha variant cases worldwide as of June 20, 2022, by country. Source: Statista
[5] John Elflein. Number of SARS-CoV-2 Delta variant cases worldwide as of June 20, 2022, by country. Source: Statista
[6] John Elflein. Number of SARS-CoV-2 Omicron variant cases worldwide as of July 4, 2022 by country. Source: Statista
Competing interests: No competing interests