How Long Will Be The Wait For A Safe COVID-19 Vaccine?

VT Padmanabhan

Adverse Effects among participants of Oxford-Zeneca Vaccin Trials in the UK

In 1922-23, about two years after the end of Spanish Flu which infected over 500 million people, the United Kingdom experienced a very small epidemic of a very rare disorder called transverse myelitis (TM).  No virus or any micro-organism behind this.  These were adverse effects from vaccinations against small pox and rabis.  After this initial disaster, during the past century,  the vaccine scientists have learned their lessons;  and today’s vaccines are much safer.  National agencies that approve the vaccine have laid down stringent rules, procedures and protocols to prevent vaccine related disasters.  However, it appears that during Covid-19 days, nothing is impossible.  Today,  TM is revisiting us and threatening the chances of getting a vaccine, which is now thought to be as the only way out of the current existential crisis.

A vaccine that nobody wants to take is not very useful – AstraZeneca’s CEO Pascal Soriot

It was painful to read that the phase-3 trials of the Oxford-Zeneca vaccine, the most promising among the nine Covid-19 vaccines under trial now, have been paused in the US, Brazil and the UK on 08 Sep 2020. A day later,  Adam Feuerstein  reported on the medical news website Statnews, that a participant in the AstraZeneca’s Phase 3 Covid-19 vaccine experienced neurological symptoms consistent with a rare but serious spinal inflammatory disorder called transverse myelitis.  This was revealed by vaccine maker’s chief executive, Pascal Soriot during a private conference call with investors set up by the investment bank J.P. Morgan.    Soriot confirmed that the participant was injected with the company’s Covid-19 vaccine and not  placebo.  Soriot also informed that the clinical trial was halted earlier also in July 2020, after a participant experienced neurological symptoms, which was diagnosed as multiple sclerosis, “deemed to be unrelated to the Covid-19 vaccine treatment”.

The first sick volunteer also had Transverse Myelitis – Company document

However, according to an Oxford-Zeneca document – the Participant Information Sheet  (PIS) dated 12th July 2020 given to the volunteers of Phase-3 trial of ChAdOx1 nCoV-19 in the UK-, the first volunteer who experienced the adverse reaction was also diagnosed as transverse myelitis and not as multiple sclerosis.  This 16 page document is part of the contract between the vaccine developers and the “10,560 adults and children across the UK”, who would volunteer for a humanitarian cause by participating in a dangerous experiment (see quote below) with their own body.  The Oxford-Zeneca reassurance about the safety of the vaccine: (Page 10):

Reactions in the nervous system are also extremely rare, but can include an illness called Guillain-Barré syndrome, a condition in which people can develop severe weakness and can be fatal. These adverse events have not previously been seen following administration of similar vaccines using ChAdOx1 as a viral vector, but one volunteer in the trials of ChAdOx1 nCoV-19 developed symptoms of transverse myelitis (inflammation in the spinal cord), which has not required medical treatment and is being investigated, though the cause is uncertain.

So, even before ascertaining the cause of the adverse effect,  Astra Zeneca was allowed to go ahead with the final phase!

The CEO of Astra Zeneca confirmed that there were two adverse effects in the vaccine trial – the first one during the Phase -1 and the second one during the Phase-3 trial.  And on both these occasions, the trial was paused as part of abundant precaution.  Though the CEO is a respectable and responsible person,  the document which is part of the contract between the vaccine developers and the volunteers is more authentic.  Therefore, I presume that both the survivors were diagnosed as TM.

The Excess Risk among the Study Population

In all here are 10,560 participants in the UK Phase-3 trial.  The study group consisting of three-fourth of the participants, would be given the ChAdOx1 nCoV-19 (Covid-19 candidate vaccine) and the remaining one-third which is the control group would be administered a licensed meningitis vaccine (MenACWY) as placebo.

TM is a rare disease which is diagnosed in 300 persons a year in the UK and 1400 persons in the US.  If all the study group participants in the UK Phase-3 trial have been injected with the vaccine, about 7000 healthy children and adults would have received the experimental vaccine.  The company claims that 2,000 persons were given the same vaccine during the Phase-1/2 trials.  This means, 9,000 persons in the UK have received the vaccine.  The incidence and the relative risk is estimated in table 1 below:

Cohort	Subjects	Cases	Per 1000	Excess Risk
Oxford Zeneca Expt	9000	2	0.2	41
Background incidence	56000000	300	0.005

In the Oxford Zeneca experiment involving 9,000 healthy volunteers, there are two cases of TM, which is 0.2 per 1000 subjects.  The background annual incidence of TM in the UK is 0.005 per 1000.  The risk among the participants in 41 times higher the background.  Oxford-Zeneca has since stated that diagnosis of the patient in the Phase-3 trial is not confirmed.  If her disease is not TM, the excess relative risk is 20 times.  Even that is not very reassuring as TM and MS are not independent, unrelated diseases.  The website of the US National Organisation for Rare Diseases says:

“TM can be the presenting feature of MS. In individuals with acute partial TM and normal brain MRI, about 10-33 percent develop MS over a five to ten-year period. If the brain MRI shows lesions, the transition rate to clinically definite MS is known to be quite high, in the range of 80 to 90 percent within a few years. Those who are ultimately diagnosed with MS are more likely to have asymmetric clinical findings, predominant sensory symptoms with relative sparing of motor systems, MR lesions extending over fewer than 2 spinal segments, abnormal brain MRI, and oligoclonal bands in the CSF.

History of Vaccine induced TM

There are reasons for vaccination makers to be concerned about the two cases of TM among the vaccine trial participants in UK.  The US National Organization of Rare Diseases (NORD) gives a historial perspective of TM:

In England between 1922 and 1923 more than 200 post-vaccinal cases (of TM)were noted as complications of the smallpox and rabies vaccines.

Review Article in Pubmed

S. Kivity, M. Szyper-Kravitz and colleagues conducted a systematic review of PubMed, EMBASE and DynaMed journals published between 1970 and 2009 and found 37 reported cases of transverse myelitis associated with different vaccines including those against hepatitis B virus, measles—mumps—rubella, diphtheria—tetanus—pertussis and others, given to infants, children and adults. In most of these reported cases the temporal association was between several days and 3 months, although a longer time frame of up to several years was also suggested. The authors conclude that “although vaccines harbor a major contribution to public health in the modern era, in rare cases they may be associated with autoimmune phenomena such as transverse myelitis”.

What is traverse myelitis (TM)?

Transverse myelitis is a serious condition involving inflammation of the spinal cord that can cause muscle weakness, paralysis, pain and bladder problems. In rare instances, vaccines have triggered cases of transverse myelitis; although it can also be caused by viral infections.   The description of the diseases given by myelitis.org.uk , a patient support group is given below:

The main symptoms of TM are muscle weakness in the legs (and, less commonly, in the arms), change in sensation (unusual feelings) in the lower half of the body, pain, and problems with the bowel and bladder. People might also experience fever, headache, tiredness, muscle spasms (spasticity), and a general feeling of being unwell. But symptoms vary depending on what section of the spinal cord is affected. 5. Recovery is difficult to predict. Around one third of people with TM will make a good or full recovery. Another third will experience some recovery and may have a moderate degree of disability. The remainder will make little or no recovery and have a permanent disability.

The Issues of transparency and Credibility

In a report dated 09 Sep 2020, the science journal Nature says that vaccine studies have protocols that specify what type of events trigger a pause, after which there is a process for investigating whether the event is related to the vaccine, AstraZeneca study protocols have not been made public.  The reporters Phillip, Cryanosky and Mallapaty then quote  Paul Komesaroff, a physician and bioethicist at Monash University in Melbo ourne, Australia:

“Details of the adverse event, including how serious it is and when it happened, have not been reported by Oxford or AstraZeneca.  Given the stakes involved in the development of a safe, effective vaccine, all of the study’s details should be made public.  The trials are all publicly supported, the disease is posing the greatest threat to humanity in a hundred years, the drug-development processes are highly politicized, and the outcome will only be a successful one if public trust can be secured and maintained.” 

Vaccine authorizations in Banana Republics?

In July 2020, the vaccine authorizers found a disease which has been associated with vaccines for nearly a century.  Even without ascertaining the cause of that disease, the vaccine makers claimed that it is unrelated to the molecule they injected into the body of the volunteer.  And the team was allowed to proceed with the Phase-3 trial.  In the phase-3 trial, the same disease surfaces in another volunteer.  One wonders why these tests?  They could have done what Russia has done!