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Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots

BMJ 2021; 372 doi: (Published 11 March 2021) Cite this as: BMJ 2021;372:n699

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Rapid Response:

Re: COVID vaccines and thrombotic events: is mRNA translation and spike protein synthesis by platelets a real possibility?

Dear Editor

This is in response to the comments from Professor Paolo Gresele [1] on our rapid response, ‘CoViD Vaccines and thrombotic events: Possibility of mRNA translation and spike protein synthesis by platelets?’ [2].

First, there is evidence to suggest that viruses like Dengue, influenza, and HIV can infect platelets, and there is a preliminary evidence of the presence of SARS-CoV-2 in the platelets in CoViD-19 patients that Professor Gresele also agreed in his response. The study from Bury et al [3] that did not detect the presence of SARS-CoV-2 in CoViD-19 patients was only conducted in 24 patients, of which only 4 had mild thrombocytopaenia. This needs confirmation in a large cohort study, in particular, in CoViD-19 patients with thrombocytopaenia.

Second, the term ‘genetic vaccines’ also include mRNA based CoViD-19 vaccines (e.g., Pfizer, Moderna). Platelets are anucleate cells that continue to defy conventional logic and are involved in mRNA translation and protein synthesis [4]. It is likely that mRNA vaccines can directly infect platelets and mRNA translation and spike protein synthesis leading to an autoimmune response against platelets. There have been at least 43 cases of immune thrombocytopenia recorded in VAERS database with Pfizer and Moderna CoViD-19 vaccines [5], and there is at least one death reported with immune thrombocytopenia after Pfizer CoViD-19 vaccine [6].

Third, the viral vector CoViD-19 vaccines (such as Ox/AZ, Sputnik-V, CanSinoBIO, Janssen/J&J) may still infect megakaryocytes, the precursor cells for platelets. The platelets have a very short life span (~10 days) and an autoimmune destruction of megakaryocytes may lead to a severe thrombocytopaenia. Many viruses are previously known to infect bone marrow, for instance hepatitis, Epstein-Barr, cytomegalovirus, HIV.

Fourth, although the viral vectors used in the vaccines are silenced (replication deficient), each dose of the vaccine contains a very high viral load (e.g., 50 billion viral particles/dose in Ox/AZ CoViD-19 vaccine and 100 billion viral particles/dose in Sputnik-V). The viral particles are unlikely to be confined to the muscles at the injection site; they are free to distribute across the body and drain through lymphatic system; their apparent volume of distribution is likely to be very high. The biodistribution of ChaAdOx1 containing HBV in BALB/c mice (study 0841MV38.001) indicated highest viral levels at the injection site, but low levels of virus were still detected in all other tissues after 24 hours of injection (blood, brain, heart, inguinal lymph node, kidney, liver, lung, gonads, and spleen; CNS, peripheral nerves or bone marrow was not studied); biodistribution beyond 24 h post dose was not measured. The biodistribution of ChAdOx1 nCoV-19 following intramuscular injection in mice (study 514559) was ongoing at the time of regulatory approval [7]. The study 514559 aimed to examine the biodistribution of ChAdOx1 nCoV-19 in bone marrow, brain, spinal cord, sciatic nerve, and other body tissues; we shall look forward to the study results. For COVID-19 mRNA Vaccine BNT162b2 (Pfizer), the biodistribution studies were not conducted, however, surrogate studies with luciferase and solid-lipid nanoparticles confirms a biodistribution to the liver and other body tissues beyond the administration site [8].

Fifth, there are reports of antibodies present in CoViD-19 patients that activated platelets [9] and patients with thrombocytopenia following Pfizer and Moderna CoViD vaccination showed favourable response to immune thrombocytopenia directed therapies (corticosteroids and IVIG) [10]. Recently, scientists from Oslo identified an antibody from vaccinated individuals which they suspect being responsible for attacking platelets and causing recent thrombotic events [11]. This discovery also supports our hypothesis [2] that CoViD genetic vaccines may have a direct role in spurring autoimmune response against platelets that may clinically manifest in thrombocytopenia, haemorrhage, and blood clots.

We would like to reiterate that vaccines are one of the great discoveries in medicine that has improved life expectancy dramatically. Nevertheless, genetic vaccines are new, and their long-term safety evaluation is a key to identify potentially contraindicated group of subjects, for instance patients with history of blood disorders, past or current thrombocytopenia or pre-existing immunological conditions.


Competing interests: No competing interests

20 March 2021
Subject Leader in Pharmacy
University of Huddersfield, UK