Blood clots and hemorrhage reported with COVID-19 vaccines
COVID-19 vaccines, especially the genetic vaccines among them, have raised worldwide concerns over the reported events of hemorrhage, blood clots, and immune thrombocytopenia. [1]
Genetic vaccines use either adenovirus vector or mRNA. This genetic technology, instead of constructing a new vaccine from scratch, simply carries the genetic material — DNA or RNA — into a cell. The genetic material can then code for specific proteins from a virus.
The genetic material in Pfizer and Moderna (mRNA) vaccines is RNA, whereas the genetic material in the J&J and AstraZeneca vaccines is DNA. However, both technologies perform the same function — encode the data to produce the SARS-CoV-2 spike protein.
DNA vaccines for COVID-19 have been described in detail in the literature. [2]
Adenovirus vaccines (Johnson & Johnson, AstraZeneca, Sputnik) use adenovirus as a vector that carries the DNA, which the vaccine recipient will use to first make RNA and then the spike protein of the SARS-CoV-2. But once the needed function is performed, the host body degrades both — DNA and RNA — without letting either of them affect our chromosomes.
What could be the reason behind the observed hemorrhage and blood clots?
First possibility: Molecular mimicry
In molecular mimicry theory, the pathogen-derived molecules are so similar to self-molecules that in the process of activating immune cells against the pathogen, they also activate the autoreactive immune cells. Autoreactive immune cells act against the host himself. In other words, the similarities between foreign and self-peptides favor the activation of autoreactive T or B cells by a foreign-derived antigen in a susceptible individual. Out of these, autoreactive T cells play the main role. However, molecular mimicry need not always result in a deleterious stimulus for the immune system, it may help to induce immune tolerance too. [3]
Immune thrombocytopenia (ITP), an autoimmune condition characterized by low platelet counts, can lead to internal bleeding in the brain. SARS-CoV-2 can induce ITP in COVID-19 patients. Coagulopathy has been a major contributory factor to COVID-19 mortality. Even Helicobacter pylori, H3N2 influenza virus, and the Dengue virus can induce ITP. [4]
Researchers have postulated that the host-antibodies produced to clear the virus can cross-react with surface antigens on platelets or megakaryocytes. The same mechanism could be possible with vaccine-induced antibodies, which act on the platelet surface antigens leading to platelet-destruction induced thrombocytopenia [4].
Second possibility: Direct destruction
Platelets are known to synthesize proteins intracellularly and this protein synthesis can alter the phenotype and functions of platelets. [5] This leads to two further possibilities.
a. RNA viruses like SARS-CoV-2 can directly infect platelets and mRNA translation within platelets could generate an autoimmune response against platelets. Dengue virus infection has shown ITP and subsequent internal hemorrhages in the brain. [1]
b. Similarly, genetic CoViD vaccines may also directly infect platelets and trigger mRNA translation in them, leading to intracellular spike protein synthesis. This may lead to an autoimmune response against platelets and their subsequent destruction. ITP has been previously reported with other vaccines, such as flu, poliomyelitis, pneumococcal, hepatitis, MMR, and rabies. [1]
Current status:
Thirty-seven blood clot cases were reported in people who had received the AstraZeneca vaccine.
Denmark, Norway, Bulgaria, Iceland, France, Germany, Italy, Spain, Portugal, Slovenia, and Cyprus suspended all use of the vaccine, whereas Austria, Estonia, Latvia, Lithuania, and Luxembourg paused the use of a single batch of a million doses of the vaccine. [6]
European Medicine Agency (EMA) report has found, as of 17 March, seven cases of blood clots in multiple blood vessels and 18 cases of cerebral venous sinus thrombosis. This comes out of more than seven million people vaccinated in the EU and 11 million in the UK. In the general population, about 100 000 people in the EU, and 3000 people in the UK develop blood clots every month. [7] This shows how rare the complication is.
Based on these numbers, the EMA has concluded that the Oxford-AstraZeneca covid-19 vaccine is not linked to an increased risk of blood clots and is both safe and effective. [8]
Previously, no serious adverse effects were reported from AstraZeneca clinical trials for the ChAdOx1 nCoV-19 vaccine, which demonstrated an acceptable safety profile. [9]
References:
[1] Merchant H. CoViD Vaccines and thrombotic events: Possibility of mRNA translation and spike protein synthesis by platelets? (Response to BMJ 2021;372:n699) (Published 15 March 2021)
[2] Silveira MM, Moreira GMSG, Mendonça M. DNA vaccines against COVID-19: Perspectives and challenges. Life Sci. 2021 Feb 15;267:118919. doi: 10.1016/j.lfs.2020.118919. Epub 2020 Dec 19. PMID: 33352173; PMCID: PMC7749647.
[3] Rojas M, Restrepo-Jiménez P, Monsalve DM, Pacheco Y, Acosta-Ampudia Y, Ramírez-Santana C, Leung PSC, Ansari AA, Gershwin ME, Anaya JM. Molecular mimicry and autoimmunity. J Autoimmun. 2018 Dec;95:100–123. doi: 10.1016/j.jaut.2018.10.012. Epub 2018 Oct 26. PMID: 30509385.
[4] Wise J. Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots. BMJ. 2021 Mar 11;372:n699. doi: 10.1136/bmj.n699. PMID: 33707182. (Published 11 March 2021)
[5] Weyrich AS, Schwertz H, Kraiss LW, Zimmerman GA. Protein synthesis by platelets: historical and new perspectives. J Thromb Haemost. 2009 Feb;7(2):241–6. doi: 10.1111/j.1538–7836.2008.03211.x. Epub 2008 Oct 29. PMID: 18983498; PMCID: PMC3027201.
[6] Mahase E. Covid-19: WHO says rollout of AstraZeneca vaccine should continue, as Europe divides over safety. BMJ2021;372:n728. doi:10.1136/bmj.n728 pmid:33727218
[7] Mahase E. Covid-19: AstraZeneca vaccine is not linked to increased risk of blood clots, finds European Medicine Agency. BMJ. 2021 Mar 19;372:n774. doi: 10.1136/bmj.n774. PMID: 33741638.
[8] European Medicines Agency. COVID-19 Vaccine AstraZeneca: benefits still outweigh the risks despite possible link to rare blood clots with low blood platelets. 18 Mar 2021. https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-benefits-still-outweigh-risks-despite-possible-link-rare-blood-clots.
[9] Voysey M, Clemens SAC, Madhi SA, et al; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99–111. doi: 10.1016/S0140–6736(20)32661–1. Epub 2020 Dec 8. Erratum in: Lancet. 2021 Jan 9;397(10269):98. PMID: 33306989; PMCID: PMC7723445.
