Orders of magnitude

Updated 07/04/2021 for revised MHRA figures.

At the beginning of April, the MHRA published an analysis of vaccine safety reports in the UK and concluded that despite now finding increased evidence of rare blood clots following administration of AZD1222 from AstraZeneca (consistent with previous reports from Europe) the benefits of vaccination still outweigh the risks. This report was followed up by press-briefing on 7th April acknowledging the link between the vaccine and rare blood clots was "getting firmer". In a UK context this complication remains a remote possibility; up to 31st March UK found 79 instances of CVST or other low-platelet thrombosis out of 20 million doses given, representing a risk of around 1 in every 253,000 doses for the complication, with an associated 19 UK deaths giving a 1 in every million dose risk of death. Out of an abundance of caution the UK vaccination program will offer under-thirties an alternative vaccine, whilst continuing largely as before other respects.

The differing UK experience appears to have been at least partially a simple time-lag, and the MHRA is now finding the same post-vaccination condition others have reported. One question is why would the UK see this later than other European countries? The UK's much larger rollout prompted the understandable first reaction that the European reports could simply prove random clusters. When many doses of any medication are given globally, local post-treatment clustering in relatively common categories of illness is bound to arise from time to time. Indeed, as Stephen reported, we'd expect more clotting events to occur by chance than were actually being found post-vaccine. However, that lack of a material increase in clotting disorders in general, did not preclude increased incidence of the much rarer sub-category of CVST and low-platelet thrombosis most often in younger people, most often in women under the age of 55, arising within three weeks of vaccine administration. The younger age-range of incidence likely contributed to the time-lag. Some EU countries initially felt the AstraZeneca vaccine trials were unproven for older age groups and as a result, initially applied the vaccine to a younger cohort. Such an approach would naturally surface this problem earlier than the UK stance of following JCVI (Joint Committee on Vaccination and Immunisation) advice and tackling cases broadly in order of decreasing age, starting with those in care homes and over eighty years of age. Now only one important problem remains: what triggers this extremely rare, extremely serious complication, and what can we do about it?

It goes without saying that any vaccine-related complication must be thoroughly investigated. Researchers in Germany have already made pre-print findings available noting that the syndrome bears strong similarities to an already known condition: heparin-induced thrombocytopenia and thrombosis (HITT). In HITT, low platelet count arises after administration of the anticoagulant heparin and is followed by the emergence of new or worsening blood clots. The commonalities between this condition and the post-vaccination reports, led the researchers to propose the name vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). The condition should be amenable to the same treatment options as HITT, in particular to the use of a specific range of non-heparin-based anticoaguants and high-dose immunoglobulin, and it is hoped these findings will spur improvements both in recognition and treatment when relevant symptoms arise between 5 and 14 days of vaccination.

On what we know now, how should we assess this level of risk? From a UK perspective, consider that at the time of writing ONS-recorded COVID-19 related mortality figures show over 149,000 deaths listed Covid-19 on the death certificate, with 126,000 of those occurring within 28 days of a positive test. Against a 2019 mid-year population of 66.8 million, the UK has already lost between 1 in 450 to 1 in 530 of the entire population to COVID-19. Considering the wider issue of morbidity, ONS estimates for the period ending 6th March 2021 show that 1.1 million UK citizens are living with symptoms of so-called long COVID, representing a potentially debilitating burden on around 1 in 60 of the UK population. The UK/MHRA position is therefore easily justified by the empirical facts: vaccination mitigates the near-and-present danger of COVID-19, in return for a very low risk of post-vaccine complications.