CoViD Vaccines and thrombotic events: Possibility of mRNA translation and spike protein synthesis by platelets?
Dear Editor
There have been reports of haemorrhage, blood clots and thrombocytopenia following administration of CoViD-19 vaccines [1]. The adverse events are primarily reported for genetic CoViD vaccines and have raised concerns over the safety of genetic vaccines for mass immunisation at global scale.
Immune thrombocytopenia (ITP) is an autoimmune condition characterized by low platelet counts manifested by spontaneous purpura, petechia, haematomas or fatal subarachnoid, intracerebral, or other internal bleeding. ITP secondary to CoViD-19 have been reported in many patients with CoViD-19 [2] and coagulopathy have been a major contributing factor to the high mortality associated with CoViD-19.
Besides SARS-CoV-2, various other pathogens are known to induce ITP, notably Helicobacter pylori, H3N2 influenza virus and the Dengue virus. It has been proposed that the antibodies produced by the body to clear the virus have a potential cross reactivity with surface antigens on platelets or megakaryocytes. This molecular mimicry had been proposed in the past as a classic mechanism responsible for the vaccine associated ITP. Antibody bound platelets and megakaryocytes undergo reticuloendothelial phagocytosis and a direct lysis by cytotoxic T-cells leading to thrombocytopenia [3].
Platelets are anucleate cells that continue to defy conventional logic; they are involved in mRNA translation and known to synthesise proteins for over fifty years [4]. In authors opinion, it is highly likely that RNA viruses can directly infect platelets and mRNA translation within platelets is a possible explanation for the autoimmune response against platelets instead of previously proposed molecular mimicry theory.
This is also a likely explanation for the thrombocytopaenia prevalence in patients infected with Dengue virus. Many patients with Dengue fever recover from thrombocytopaenia over time suggesting a highly selective immune response against infected platelets or megakaryocytes. In some patients with Dengue virus infection, this autoimmune response can manifest as ITP and consequent subarachnoid, intracerebral, or other internal haemorrhages, during the course of the disease result in fatal outcomes.
It is, therefore, not unreasonable to hypothesise that the genetic CoViD vaccines may also directly infect platelets and megakaryocytes triggering mRNA translation and consequent spike protein synthesis intracellularly. This may lead to autoimmune response against platelets and megakaryocytes resulting in reticuloendothelial phagocytosis and direct CD8+ T cell lysis.
There have been over 150 reports of post-CoViD19 vaccination thrombocytopenia recorded in the pharmacovigilance databases at VAERS [5] and MHRA [6], and at least one confirmed death in USA which is still under investigation [7]. ITP have also been previously reported with a number of other vaccines, such as flu, poliomyelitis, pneumococcal, hepatitis, MMR, and rabies. The vaccine mediated autoimmunity was proposed to be associated with both the antigen and vaccine constituents, for instance the trace proteins from the culture media (such as yeast proteins), adjuvants, preservatives, or formulation carriers [3].
In authors opinion, it is plausible 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. It, however, requires substantial evidence to confirm this hypothesis. Vaccines are one of the great discoveries in medicine that has improved life expectancy dramatically. Nonetheless, 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. European Medicines Agency (EMA) continues to investigate the recent thrombotic events in Europe, and we shall look forward to their findings [8].
Rapid Response:
CoViD Vaccines and thrombotic events: Possibility of mRNA translation and spike protein synthesis by platelets?
Dear Editor
There have been reports of haemorrhage, blood clots and thrombocytopenia following administration of CoViD-19 vaccines [1]. The adverse events are primarily reported for genetic CoViD vaccines and have raised concerns over the safety of genetic vaccines for mass immunisation at global scale.
Immune thrombocytopenia (ITP) is an autoimmune condition characterized by low platelet counts manifested by spontaneous purpura, petechia, haematomas or fatal subarachnoid, intracerebral, or other internal bleeding. ITP secondary to CoViD-19 have been reported in many patients with CoViD-19 [2] and coagulopathy have been a major contributing factor to the high mortality associated with CoViD-19.
Besides SARS-CoV-2, various other pathogens are known to induce ITP, notably Helicobacter pylori, H3N2 influenza virus and the Dengue virus. It has been proposed that the antibodies produced by the body to clear the virus have a potential cross reactivity with surface antigens on platelets or megakaryocytes. This molecular mimicry had been proposed in the past as a classic mechanism responsible for the vaccine associated ITP. Antibody bound platelets and megakaryocytes undergo reticuloendothelial phagocytosis and a direct lysis by cytotoxic T-cells leading to thrombocytopenia [3].
Platelets are anucleate cells that continue to defy conventional logic; they are involved in mRNA translation and known to synthesise proteins for over fifty years [4]. In authors opinion, it is highly likely that RNA viruses can directly infect platelets and mRNA translation within platelets is a possible explanation for the autoimmune response against platelets instead of previously proposed molecular mimicry theory.
This is also a likely explanation for the thrombocytopaenia prevalence in patients infected with Dengue virus. Many patients with Dengue fever recover from thrombocytopaenia over time suggesting a highly selective immune response against infected platelets or megakaryocytes. In some patients with Dengue virus infection, this autoimmune response can manifest as ITP and consequent subarachnoid, intracerebral, or other internal haemorrhages, during the course of the disease result in fatal outcomes.
It is, therefore, not unreasonable to hypothesise that the genetic CoViD vaccines may also directly infect platelets and megakaryocytes triggering mRNA translation and consequent spike protein synthesis intracellularly. This may lead to autoimmune response against platelets and megakaryocytes resulting in reticuloendothelial phagocytosis and direct CD8+ T cell lysis.
There have been over 150 reports of post-CoViD19 vaccination thrombocytopenia recorded in the pharmacovigilance databases at VAERS [5] and MHRA [6], and at least one confirmed death in USA which is still under investigation [7]. ITP have also been previously reported with a number of other vaccines, such as flu, poliomyelitis, pneumococcal, hepatitis, MMR, and rabies. The vaccine mediated autoimmunity was proposed to be associated with both the antigen and vaccine constituents, for instance the trace proteins from the culture media (such as yeast proteins), adjuvants, preservatives, or formulation carriers [3].
In authors opinion, it is plausible 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. It, however, requires substantial evidence to confirm this hypothesis. Vaccines are one of the great discoveries in medicine that has improved life expectancy dramatically. Nonetheless, 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. European Medicines Agency (EMA) continues to investigate the recent thrombotic events in Europe, and we shall look forward to their findings [8].
References
[1] https://doi.org/10.1136/bmj.n699
[2] https://doi.org/10.1007/s42399-020-00521-8
[3] https://doi.org/10.1007/s12026-014-8597-x
[4] https://dx.doi.org/10.1111%2Fj.1538-7836.2008.03211.x
[5] https://vaers.hhs.gov/data.html
[6] https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-...
[7] https://www.nytimes.com/2021/01/12/health/covid-vaccine-death.html
[8] https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-prac-inve...
Competing interests: No competing interests