The world is changing fast and to keep up you need local knowledge with global context.
We are indeed living in unprecedented times. The abrupt advent of Covid-19 was, however, only the beginning. What followed was an anomalous sequence of events that have irrevocably changed the way we live. Draconian lockdown measures, unnerving censorship and an atmosphere of fear and desperation became the norm. Faced with this, it was only natural that people would become fixated on finding an ‘antidote’ – the most obvious of which is the Covid-19 vaccine. Dr Nathi Mdladla, the author of this comprehensive article, does a deep dive into the relentless vaccine race – despite the numerous setbacks which have been encountered in relation to the vaccines. Mdladla raises those tough but salient questions that have been sidelined, stating that; ‘Irrespective of what happens, the sad ongoing problem is where science gets ignored for political expediency, which will be the real failure that most governments will be judged for in time in this pandemic’. – Nadya Swart
COVID-19 Vaccines – Was the South African Government pressured to procure potentially ineffective vaccines?
The jury on safety in the short and long term is still out…
By Dr Nathi Mdladla*
Vaccines have been touted as our only real hope for an end to the COVID-19 pandemic, after everything that held promise sequentially proved incapable of halting the scourge. In the last six months, vaccines have given hope for a return to a semblance of normalcy after everything we were told would stem the tide failed to do so.
- Non-pharmacological interventions – masks, physical distancing and frequent hand-washing – failed to “flatten the curve”.
- Hard lockdowns led to further lockdowns as soon as they were lifted as the virus surged once more.
- Expensive “cures” with theoretically effective mechanisms of action – hailed as potentially life-saving – also progressively failed. Remdesivir, Tociluzimab, Interferon and others come to mind.
- Corticosteroids made world headlines and were supposed to ameliorate the effects of the pandemic, but their window of opportunity was found to be too limited and their modest 25% relative survival benefit meant many more would still die.
- Hydroxychloroquine was one of the first major repurposed and promising agents, but it suffered the initial skeptics’ assault and was soon shelved.
- Another repurposed drug, Ivermectin, was investigated in the low-to-middle-income countries as a potential therapy and showed great promise. It has withstood a barrage of punches with regards to its role, and the jury is still out on its effectiveness.
16 months into the pandemic, we still do not have a WHO-declared cure for COVID-19, but in the meantime the drive towards vaccine creation has been of a magnitude never seen in medicine before. Companies who joined the race towards vaccine manufacturing saw their share prices balloon and surge with every positive result on efficacy they shared. Governments stumbled and stepped over each other, racing to be at the front of the queue to receive the first tranches of vaccines. Human “solidarity” – the epitome of the first surge – suddenly got buried in the ensuing dust of the scramblers, as governments sought to prioritise their citizens over and above the plight of equally deserving low-and-middle-income country (LMIC) citizens with proportional risk of severe disease and death.
South Africa had faced a relatively mild first surge in comparison to the rest of the world. We were testing aggressively for a LMIC country and at some point were on par with the UK in the percentage of tests performed. We registered the lowest mortality relative to positive test results and per 100,000 of the population or any other metric used at that stage. Initial fears of huge mortality rates proved unfounded, and South Africa was fortunate to register mortality figures that surprised many. A lot of factors were thought to contribute to this, including our younger population (a view held by this author), higher exposure to previous coronaviruses which may have conferred some degree of protection, our overcrowding conditions allowing us to reach antibody levels close to herd immunity earlier, or some special attribute that made us a world “miracle” (as mentioned by the former MAC Chair)!
It is no surprise then, that when the high-income countries with significantly higher mortality rates were scrambling for vaccines in preparation for their second and third waves, vaccines seemed to be the obvious antidote and means to salvation. The major players (UK, USA, Germany, China, Russia and India) had pragmatically put their money forward to guarantee themselves first dibs when the time came for the classic “dog eats dog” scenario to ring true. As soon as vaccines became available, which coincided with the peak and decline in the second wave in most northern hemisphere countries (which coincidentally also have the bulk of the high-income countries), hoarding of vaccines by the rich became the norm. Chile is probably the only country in the Southern Hemisphere to have bucked the trend and made early concessions with vaccine suppliers to get the first supply of vaccines. Interestingly, they had to make some major concessions – some of which are still wrapped in secrecy – to achieve this. Israel and The UAE were the leaders in the Middle East.
South Africa, like all other LMIC’s, sat back and basked in the glory of its lower mortality numbers from the first surge. All pointers were that our next major surge should come in the winter of 2021 and a period of calm through the festive season was expected (again, a view shared by this author). The opening of borders and the arrival of mutated strains from overseas countries, who were already in the middle of their second waves, disturbed this expected calm and South Africa found itself in the midst of a COVID-19 surge in the middle of summer. We were in no way near to making any form of commitments towards the acquisition of vaccines, reasonably in my opinion bearing in mind what had happened elsewhere, and our first surge described above. Why would anyone invest billions of Rands in a vaccine for a disease with a 99% recovery rate and around 2% mortality rate in those testing positive? No one had predicted the mutated variants that filled our second surge, especially considering what we have always known about coronaviruses being known to mutate slower than influenza viruses.
South Africa had to play catch-up as the citizenry got agitated and impatient, and wondered where our vaccination strategy was. As the second surge raged on, the disease burden intensified as a result of sheer numbers – overwhelming an already over-stretched healthcare system. Hospital admissions and mortalities became uncontrollable, and the desperation quickly reached fever pitch. Rapid deals were made with Oxford-AstraZeneca to supply our first million doses of the Oxford-AstraZeneca vaccine in February 2021. Politicians graced newspaper front pages and news headlines as they received the Indian made vaccine at OR Tambo International Airport in the early hours of one fateful morning. This was indeed the beginning of an essential new dawn of hope.
Unfortunately, on the evening of the 6th of February 2021, when the results of a small trial on the efficacy of the O-AZ vaccine were published, it became clear that the vaccine was less than 25% effective against the predominant new variant in South Africa. It immediately became apparent that South Africa had just bought a supply of a million spoilt eggs, and had to do something drastic to save face and be able to proceed with the planned rollout.
Into this quagmire entered two saviours wearing their respective vaccine manufacturer capes to save the damsel in distress that was South Africa at that moment. I’m certain that the scramble that happened over the next 12 hours after the study results came out will be the stuff of movies one day – “How two vaccinologists saved the South African government from embarrassment”. Prof Shabir Madhi represented Oxford-AstraZeneca as their Lead Investigator to explain the unfortunate results of their study, whilst Prof Glenda Gray represented Johnson and Johnson (J&J) which up to that point was still unregistered in the country. It appeared as though she had moved heaven and earth to secure the 500,000 doses. This commenced a project which was called by various names; from the “Phase 3b Study”, to the “Fast-track access for health care workers” to the ”vaccine rollout”, depending on who was taking credit or trying to obscure what was actually going on. Whatever the terminology was, all parties involved were gaining from Oxford-AstraZeneca’s misfortune – J&J could get an expedited trial going with 500,000 possible subjects, and the government could claim they were rolling out the vaccine to healthcare workers.
Typical of politics, despite the fact that Prof Gray had recently been publicly vilified and sacrificed at the court of public opinion for her views on the sometimes senseless lockdown regulations, she was now the darling of the country – she held the same platform with the COVID-19 MAC Chair and the Minister of Health whom she had recently been at loggerheads with. She had been ousted from the MAC and left out to dry – yet she was now the apparent saviour. It is interesting that the MAC Chair stepped down within a month and has subsequently moved on to better things at the WHO…
From this point on it was once more a scramble to salvage face. SAHPRA could not permit the J&J vaccine to be rolled out in South Africa as it was not yet a registered product and still needed to go through its 12 week cumbersome and protracted registration process. It would seem, however, that insider know-how and connections to regulators, almost certainly shoulder-propped by desperate politicians, allowed the fast-tracking of a win-win solution of a “Phase 3b Trial”/“Rapid Access program”/“Vaccine Rollout Program” dependent on which particular lens you were looking through. For the SAMRC/SAHPRA/J&J contingent, this was a Phase 3b Trial of an as yet unregistered product. For the politicians, it was a vaccine rollout made to make sure that the President looked like he had saved the day. For desperate and worried healthcare workers, and other parties with no vested interest, this was a rapid access program made to ensure that health workers got vaccinated early and were protected.
South Africa was at the end of the second surge at the beginning of February 2021, and as such there was no need to rush to sign any major contracts with any vaccine supplier. Based on the experience of our first “wave”, we would have been justified to wait before forging ahead. Even if we felt the pressure, we at least had another 2-4months before our next surge – depending on how pessimistic you were, or what informed your take on factors affecting a now-predictable increase in cases. Why the rollout/fast access/Phase 3b Trial had to be embarked upon so quickly is anyone’s guess. It is, however, apparent that political pressure and interference are the very same elements that have made sure that our strategies during this pandemic have felt less like something informed internally, and more like cut-and-paste recommendations from elsewhere (WHO/WEF).
The Pfizer and Moderna vaccines were the leaders in high “efficacy” at this stage, with each boasting more than 90% effectiveness against COVID-19. The O-AZ and J&J had yet to catch on the language used to decide efficacy and were declaring modest findings in the regions of mid-50’s to mid 60’s efficacy. Unfortunately, countries with deep pockets had already laid claim to the Pfizer and Moderna vaccines, so that LMIC’s could only access a few thousand doses if they applied – or they had to wait for the second half of 2021 to have a promise of any supplies. To even receive this promise, they had to sign confidentiality agreements and absolution contracts with Pfizer in order to be guaranteed delivery. Up to this day, Chile has not disclosed to its citizens what the contracts it signed with vaccine makers for its expedited access mean for its sovereignty.
The initial Phase 3b Trial (the correct term for what was happening) was also not without controversy. This was supposed to be a voluntary process, targeting healthcare workers (the drug was still not registered by SAHPRA) with informed consent supposed to be given to trial participants. It was implied that there would be phases to access – with high-risk patient-facing healthcare workers given first priority – and with the process being rolled out until all healthcare workers who wanted to be vaccinated got the vaccine. From the moment the process started, through the EVDS registration system, it became clear that the process was inherently and disturbingly flawed:
- The categorisation of a healthcare worker was itself problematic as registration on EVDS required an HPCSA number.
- Patient-facing healthcare workers were assumed to take precedence over other essential workers such as cleaners, porters and administrative staff.
- Only healthcare practitioners affiliated to university hospitals were originally given access to vaccines, as the programme was essentially still considered a trial (private practitioners were eventually allotted a limited supply of vaccines).
- Jumping of queues became the order of the day – non-patient facing physicians found a way to lie on EVDS and move to the front of the queue, while some just pitched up and got vaccinated with no questions asked.
- The EVDS system rejected clinicians working in COVID wards and other practitioners deemed high risk by exposure and age/comorbidities. This caused significant consternation amongst physicians as those who jumped the queue were quick to boast about it, with photos appearing on the social media accounts of private practice medical practitioners proudly receiving their jabs.
- Other workers in private healthcare settings who could not drive themselves to the academic vaccination centres (porters, cleaners and nurses) had to undergo the stress of knowing that the doctors they had previously faced the same dangers alongside were now vaccinated whilst they were not. Worse still, doctors and their secretaries who faced less danger got vaccinated before them.
- Once it was obvious that the process could be bypassed, more and more undeserving healthcare workers and non-healthcare workers (secretaries, spouses and children of doctors, including employees in non-clinical settings) were being snuck in through EVDS.
- At the tail end of the study, it seemed that anyone could get in and get the vaccine by bypassing the controls – nobody really knows how many of the approximately 500,000 J&J doses dispensed have actually been assigned to healthcare workers despite public declarations.
At the end of March, we were sitting with a poorly managed trial with no hope of meaningfully informing SAHPRA about the licensure of the J&J vaccine. Interestingly, SAHPRA had already given an emergency use license to J&J before any of the results around safety of the vaccine had been published. I believe that we are in no better position now than we were then – considering all the breaches of protocol that have happened with the J&J Phase 3b Study. If one were to be pedantic about which conditions need to be met for a trial’s results to meaningfully qualify and be considered as meeting required standards, we find ourselves a long way from meeting the goal posts on this case. If the noble agenda of allowing healthcare workers expedited access for an intervention that was supposed to save lives – and this is what the study principals believed in – the wording could have still been transparent enough to capture this. All that would have been required after that is a transparent communication and consenting process that laid bare the investigators’ biases against the possible risk, so that everyone involved knew what was at stake. This unfortunately did not happen, and we were left with a pseudo-rollout where healthcare workers and employers believed that this was a proven intervention with no downside! Nothing could be further from the truth…
Between February 7th and at the time of writing of this article (6th March 2021, and updated again on the 16th of May 2021), numerous setbacks have been encountered by vaccines, their manufacturers and those lobbying governments to procure them en masse without asking questions:
- side effects, especially anaphylaxis in the case of the Pfizer vaccine, are still a big concern and possibly explain the attenuation in individuals getting their second dose;
- lack of effectiveness with regards to mutations, as happened with the O-AZ vaccine, published in the leaked Financial Times article on the 6th of February 2021 and recently formally in the New England Journal of Medicine on the 20th of May 2021;
- the need to shift goal posts from vaccine as a mean of infection prevention (it soon became clear that most of these vaccines could not do that), to prevention of severe disease requiring hospitalisation and death (post-diction and extrapolation) – which are end-points not originally studied for these vaccines as described by and discussed in this British Medical Journal article;
- catastrophic complications like blood clots with the O-AZ vaccine and J&J vaccines as described in this Wall Street Journal Article;
- failure and breakthrough infections in the real world setting of vaccines in countries where massive vaccination drives had been achieved (for example in Chile, which has forced lockdowns in spite of successful vaccine campaigns);
- duration of protection and the rapid requirement of booster doses (in the case of J&J single dose vaccine as described by Prof Madhi in this IOL article).
The unavoidable questions then are the ones some poised early on when mutations started emerging – what is/was South Africa’s strategy around vaccination:
- target populations;
- what we could afford;
- what was meaningful for SA;
- assessment of real necessity.
We have been embarrassed by the O-AZ debacle and should be glad we did not have to discuss blood clot issues with it in SA. We have procured 20million Pfizer doses even though laboratory studies have shown that it is not effective against the currently predominant variant in South Africa. The research from independent investigators from Israel in a Forbes article is shared here.
Interestingly, within a month Pfizer has publicly shared results that its vaccine is 100% effective against this strain from its own studies. The J&J challenge may or may not manifest, but it leaves everyone worried if indeed its efficacy were to be shorter than 4-6months – meaning all currently vaccinated healthcare workers will need a booster dose, as declared by Prof Madhi.
Irrespective of what happens, the sad ongoing problem is where science gets ignored for political expediency, which will be the real failure that most governments will be judged for in time in this pandemic. We made similar mistakes during the initial lockdown interventions, we compounded the mistakes with our testing strategies and now we are showing that we are incapable of making decisions on accountability with vaccines. We have been prepared to ignore lessons from history, whilst continually proclaiming that we are dealing with a novel virus. We’ve gone as far as forgetting about what drives big pharmaceutical companies – their share price, a perverse incentive that dictates narrative. It’s as though the lessons on what greed can do, learnt all too well through the opioid crisis and the financial markets crisis, have been forgotten (some of the current vaccine makers were involved in these scandals).
A few of the currently available vaccines will prove to be effective with minor side effects, but that’s not all of them. Our belief in vaccines being the silver bullet has unfortunately created so much fear and made us believe that any discussion pointing to vaccine inadequacies is a driver of hesitancy or is proof that those who question them are anti-vaxxers. Phase 2&3 trials are financed, driven and run by vaccine makers and they were always meant to only help the manufacturers with licensing their product and have never been about providing efficacy and future challenges (including long term safety information). Only once vaccines have been rolled out in the community and face all the challenges of the real world could all their inadequacies be exposed. It is true that pandemic situations dictate that not all the requirements normally used out of pandemics are met, but we should not have allowed a “free license to kill” scenario unless there were absolutely no strings attached and the vaccines came at no financial cost.
As the challenges for these vaccines keep mounting, some individuals with no financial interest find themselves doing the bidding for the vaccine manufacturers and advancing spin that these companies used to pay top dollar for. From downplaying side effects to shifting of goal posts, to draconian contracts that governments are forced to sign to absolve big pharmaceutical companies; we find ourselves in unprecedented times. This is a veritable utopia for big pharma – billions of dollars stand to be made for products they’ll never be held liable for in case of failed therapy/protection and side effects – with the additional guarantee of fast-track approval and rollout of their products! To make a ridiculous situation more absurd, some of these listed companies have been given a financial boost by backing with taxpayer money. Parallels with the situation with the US banks during the 2008 financial markets crisis come to mind, although this time in reverse – we are paying upfront to lose our entire investment.
This will be like the internet bubble of the 90’s, it’s only that this time we’ll realise how we gave up our intuitive thinking, and at times allowed censorship of differing voices to allow those whose main goal was profiteering through this pandemic to do so with our full and absolute consent. Like many of our past major crashes, we’ll possibly not learn from this one as well. More worrying is that side effects have been happening and have not been captured in the detail and magnitude at which they have been happening in South Africa. This is not surprising considering that our ability to monitor and document side effects is not at the level of the developed world. We also know that even in the best equipped and serviced countries, reporting of side effects to any drug or intervention are around 1-10%, meaning that for every reported side effect, there are potentially nine more that are not picked up or reported. In South Africa, one would expect this to be even higher due to the known systemic failures of our public healthcare system. The signal of what is truly going on is often on the ground, through unsolicited reports to non-conflicted individuals and organisations. This is what has been happening in South Africa. We indeed have our fair share of brain clots, some documented and the majority probably not, but the symptomatology reported tells us they are happening. It’s interesting that even the possibility of this happening is not alluded to in official reports.
As the formal roll-out, still under emergency use authorisation, of all the currently available vaccines begins this week – we will learn more about the efficacy of the vaccine and, more importantly, about the benefit to harm balance of the intervention. Vaccines are indeed one of our best hopes for ending the pandemic, whether our current approach is the correct one can only be judged over time. We have bypassed numerous basic principles of medicine to be where we are, we’ll shortly learn if this was the right course of action…
- The views in this article are those of the author and do not represent the institution and organisations he is affiliated with. The author reports no conflicts of interest related to the topic being discussed.
- Dr Nathi Mdladla is the Associate Professor and Chief of ICU at Dr George Mukhari Academic Hospital and Sefako Makgatho University (article originally compiled on the 6th of April 2021 and updated on the 16th of May 2021)
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