The UK government has given temporary authorisation for the two dose Oxford/Astrazeneca COVID19 vaccine. This is another experimental vaccine with limited safety testing, but run against a control, the MenACWY meningitis vaccine, a vaccine already known to produce significant adverse effects. After criticism that using the meningitis vaccine as a control might mask adverse effects of the new COVID19 vaccine, an additional small study group was recruited and given a true placebo. The Oxford/Astrazeneca (O/A) trial was paused in September while serious adverse effects, later revealed to include transverse myelitis, were investigated. The Oxford group was criticised for lack of transparency, and was the focus of some derision when it was reported that a group of trial subjects had been given the wrong dose. The trial was restarted the following week.
Under UK law, it is the legal responsibility of every healthcare professional, to explain the risks and benefits to the recipient during their discussion about informed consent. Ethically and legally, the discussion must include the fact that the recipient will essentially be taking part in the vaccine’s ongoing safety and efficacy testing, and it must draw attention to the very real risk of developing antibody dependent enhancement, an immune response which would then predispose the recipient to more serious COVID19, and possibly death, if they later come into contact with the virus in the community.
Let’s look at the information contained in the government documents and related official information, since the O/A application itself is not in the public domain at this time.
The UK Government’s official website contains the associated documents and, in answer to questions from the Muslim and Jewish communities in particular, states categorically : “The MHRA (the Medicines and Healthcare products Regulatory Agency) can confirm that the COVID-19 Vaccine AstraZeneca does not contain any components of animal origin.”
The MHRA might be playing semantics here, but the official Reg 174, issued to healthcare professionals involved in dispensing this vaccine describes the active ingredient, intended to produce the immune response, as follows:
“COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 × 1010 viral particles (vp)
*Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS CoV 2 Spike (S) glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells. (A cell line grown from the kidney cells of an aborted female foetus)
This product contains genetically modified organisms (GMOs).”
This will not surprise anyone familiar with the kind of ingredients routinely used in the recommended schedule of childhood vaccines, but perhaps it ought to generate a pause for thought. At this point, it’s fair to say that the mid and long term effects of injecting a genetically modified chimpanzee adenovirus vector, produced in genetically modified human embryonic kidney cells, in the context of COVID19, is not known.
What do the experts say?
The plan is to rollout the first dose to as many people as possible and extend the second dose to 12 weeks or more, so that more people can have a first dose, while early recipients are waiting for their second dose to arrive, rather than hold up rollout until all the first dose recipients have received their second dose. There is also the suggestion that a mix and match approach will speed up the process of vaccinating the population. If the first dose was the O/A vaccine and a slow supply chain prevented a second dose in a timely manner, the Pfizer vaccine, or some other COVID19 vaccine could be given instead. Pfizer immediately responded to this suggestion stating: “…there are no data to demonstrate that protection is sustained after 21 days from receiving the first dose.” They made no comment on the possibility of adverse effects occuring as the result of such a plan.
In a round up of what the experts say at the Science Media Centre, there was much applause, in particular because the O/A product is less expensive and can be stored in a fridge, rather than requiring the extreme temperatures (-70C) required for the mRNA vaccines. This means the O/A product will be much easier to distribute throughout the developing world.
Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:
“So from Matt Hancock’s and the Oxford team’s various interviews/briefing it seems like there has been a shift away from the discussion around comparing the absolute vaccine efficacy figures (the O/A stated efficacy is significantly lower than Pfizer’s) – towards just focusing on reducing the severity of COVID-19 illness and keeping people out of hospital – even with just one dose of the Oxford AstraZeneca vaccine.” and goes on to say, “It is still yet to be seen if/how the Russian Sputnik V vaccine will be used to increase the overall efficacy of the Oxford-AstraZeneca vaccine – and whether there will be a trial to mix/match doses of different vaccines to increase overall vaccine efficacy……But above all, we need to continue with our current or even more intense restrictions on social contact and mixing to reduce the current surges in COVID-19 cases, to avoid overwhelming healthcare services, as well as making time for the vulnerable to receive their COVID-19 vaccines before they become infected.”
“When COVID-19 Vaccine AstraZeneca is given for the first injection, COVID-19 Vaccine AstraZeneca (and not another vaccine against COVID-19) should be given for the second injection to complete vaccination course.” There is no data on the efficacy or risks of mixing the vaccines. None of the vaccines currently being authorised have been through more than a few months of safety testing.
Articles in Nature and The Lancet, in early December, highlighted ongoing concerns : “from the interim analysis of these trials, we cannot yet infer efficacy in older adults, who are the group at greatest risk of severe COVID-19 outcomes.” The authors mention serious adverse reactions, including cases of transverse myelitis:
” No serious adverse events or deaths that were treatment associated occurred in ChAdOx1 nCoV-19 recipients. There were 175 serious adverse events (84 in the ChAdOx1 nCoV-19 group and 91 in the control group), three of which were possibly related to the intervention: transverse myelitis occurring 14 days after a ChAdOx1 nCoV-19 booster vaccination, haemolytic anaemia in a control recipient, and fever higher than 40°C in a participant still masked to group allocation. Two additional transverse myelitis cases considered unlikely to be related to the intervention occurred: one 10 days after the first dose of ChAdOx1 nCoV-19 was attributed to pre-existing multiple sclerosis and one in a control group that occurred 68 days after vaccination. The transverse myelitis cases resulted in temporarily pausing the trial and all participants have recovered or are recovering.”
When researching vaccine development and testing, it is interesting to notice what is considered a “serious” adverse reaction. The authors of the Lancet article state that no serious adverse events or death that were treatment associated occurred in ChAdOx1 nCoV-19 (vaccine) recipients. Then, “three were possibly related to the intervention: transverse myelitis occurring 14 days after a ChAdOx1 nCoV-19 booster vaccination”. Transverse myelitis is a serious neurological, potentially life changing, inflammation of the spinal cord, leading to paralysis.
The authors continue: “from the interim analysis of these trials, we cannot yet infer efficacy in older adults, who are the group at greatest risk of severe COVID-19 outcomes.” Questions about whether it would prevent infection and/or transmission of the virus are currently still unanswered, and yet the authors conclude that the O/A vaccine is ready to go. (When reading papers, even in such prestigous journals as The Lancet, it’s important to check the authors’ declared conflicts of interest. MDK reported grants and personal fees from Merck and grants from Pfizer, and is a subgrant recipient on an unrelated study conducted by the principal investigator of this trial. CW has received grant funding and personal fees from Merck, albeit outside of the area of work commented on here.)
Like the Pfizer vaccine, safety testing is limited and the rollout for the public is an experimental medical trial, with ongoing Phase 3 data being collected from the vaccine recipients in real time.
Warnings and Unknowns
4.3 Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
4.4 Special warnings and precautions for use (a selection)
“As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.”
Concurrent illness: “As with other vaccines, administration of COVID-19 Vaccine AstraZeneca should be postponed in individuals suffering from an acute severe febrile illness. However, the presence of a minor infection, such as cold, and/or low-grade fever should not delay vaccination.”
Thrombocytopenia and coagulation disorders: use caution for anyone with coagulation disorders or on blood thinners.
Immunocompromised individuals: it is not known what level of efficacy this group will have.
Duration and level of protection: Not yet known.
Interchangeability: No data on using different COVID19 vaccines in the same recipient.
4.5 Interaction with other medicinal products and other forms of interaction
“No interaction studies have been performed.” There has been no study done on interaction with other COVID19 vaccines. (5.1)
4.6 Fertility, pregnancy and lactation
“There is a limited experience with the use of COVID-19 Vaccine AstraZeneca in pregnant women.”
“Preliminary animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo fetal development, parturition or post natal development; definitive animal studies have not been completed yet. The full relevance of animal studies to human risk with vaccines for COVID-19 remains to be established.” Animal studies have not yet been completed.
“Administration of COVID-19 Vaccine in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.” This presumably will form part of the discussion with their healthcare professional during the informed consent requirement.
Breastfeeding: “It is unknown whether COVID-19 Vaccine AstraZeneca is excreted in human milk.”
Fertility: “Preliminary animal studies do not indicate direct or indirect harmful effects with respect to fertility.” No long term data is available.
4.8 Undesirable effects
A long list of mild to moderate adverse effects experienced by the trial subjects follows: pain at the injection site, fever, headache, muscle aches, dizziness, swollen lymph nodes, nausea, vomiting, abdominal pain, rashes, fatigue, malaise, chills and influenza like illness.
The cases of tranverse myelitis reported in the trial, are covered in this paragraph:
“Very rare events of neuroinflammatory disorders have been reported following vaccination with COVID-19 Vaccine AstraZeneca. A causal relationship has not been established.”
An experimental medical trial of unknown outcome
Nature criticised Oxford and Astrazeneca for a lack of transparency regarding the outcome of their trials, but it seems to have fallen on deaf ears. The information in the public domain at this point is government issued and lacking in detail, not surprising for the vaccine the UK government has backed with significant amounts of tax payer’s money. Most of the information that is available seems to be designed to reassure the public.
What is clear is that the claim of efficacy (70-80%) is lower than that claimed by Pfizer/Biotech for their vaccine, there is no data regarding how long any conferred immunity will last, no data regarding effectiveness in the elderly, because only a small number of trial participants were over the age of 55.
Whether the vaccine will prevent infection and / or transmission is also not yet known.
The potential for antibody dependent enhancement i.e. developing serious COVID19 on exposure to the wild virus after vaccination, is still unknown but considered by scientists to be a real risk. This immune response shut down all previous attempts to develop a vaccine for SARS-cov-1.
If you were to be harmed by a COVID19 vaccine, your only recourse is to prove vaccine harm to the government. Adverse effects occurring 4 hours or more after the vaccine make it increasingly difficult to prove a causal relationship. If you do manage to prove that harm was caused, and the adverse reaction has left you more than 60% permanenetly disabled, the government will compensate you with a one off payment of up to £120K, although the payment is tax free, it will affect any benefits you currently receive.
In these circumstances it would seem foolish not to consciously weigh up the unknown benefits against the known risks, and adjust your place in the queue accordingly.