TIME TO SUBSTITUTE EVIDENCE FOR EMOTION ABOUT VACCINE DELAYS
Dr Daniel Israel, Johannesburg-based GP
Last week, a balloon of hope that thousands of healthcare workers would be well on their way to long-awaited immunity against COVID-19 was deflated as the government announced it wouldn’t dispense the one million doses of the Oxford/AstraZeneca vaccine as planned. The vaccine’s efficacy against the 501Y.V2 South Africa variant was unveiled at just 22%.
As this development was announced, my Facebook feed became increasingly flooded with frustrated community members calling out the “inept” government for buying one million vaccines that now need to be thrown away. “Typical South Africa!”; “Trust our country to get it wrong!” These were the comments attracting the most attention.
My mind went to a mere six weeks ago, when I followed a webinar in which Professor Barry Schoub, the chairperson of the COVID-19 Ministerial Advisory Committee on coronavirus vaccines, said that the government would be taking its time to evaluate the most appropriate choice of vaccines and rollout approach in view of the complexities of the population and variants here. This would be in contrast to countries like Israel that had already dived into a mass rollout. Interestingly at the time, I also came across similar “typical inept South Africa!” comments.
Aside from the apparent cynicism that has grown in our society – perhaps from inconsistency in public policy in so many facets of public life, COVID-19 being no exception – I believe a real understanding of levels of evidence of medical research is needed here. Sound medical decisions are informed by evidence. Evidence is graded into seven levels: randomised control trials occupying levels 1 and 2, control trials without randomisation level 3, case controls level 4, large reviews level 5, single studies level 6, and expert opinions level 7. So, without getting too technical, when you visit your doctor and (s)he tells you (s)he strongly believes in a new supplement, it may be a level 7 at most.
The risky and expensive process of rolling out millions of vaccines across South Africa ought to be informed by the highest level of evidence – randomised control trials (RCTs). An RCT involves recruiting thousands of volunteers and randomising them to two groups: one that receives the vaccine and one that doesn’t. However, the volunteers ought not to know who is in which group lest their preconceived beliefs and subsequent behaviour play a role in the outcome of their results.
In the context of a COVID-19 vaccine, to test whether an Oxford/AstraZeneca vaccine would work on our population, thousands of people needed to be recruited and randomly assigned to either a placebo or a real intervention group, and then followed for months to see whether there would be a difference in incidence of COVID-19 infections between the groups.
South African mainstream medical scientists have, thankfully, always been focused on these principles with a deep commitment to recommending interventions that do no harm and work scientifically. COVID-19 has been no exception to this. So, the above process was followed.
The Wits Vaccines and Infectious Diseases Analytics (VIDA) Research Unit has run the Oxford COVID-19 vaccine trial in South Africa for months, and has raced ahead to produce results as quickly as possible. It so happens that because of the immune pressure on the SARS-CoV-2 virus to survive amongst a relatively already exposed population, the virus mutated in November 2020.
It was only due to the rigorous efforts of units like VIDA that South Africa identified the variant so quickly and soon began to evaluate whether the Oxford/AstraZeneca vaccine would work here. It also soon became apparent that 95% of all cases in the second surge of the pandemic were, indeed, this new variant.
Stuck between a rock and a hard place of procuring stock while still awaiting results, the government secured its first shipment and cautiously forged ahead. Telling results have now followed, just before implementation.
We are all deeply disappointed by the failure in the efficacy of the Oxford/AstraZeneca vaccine against our local strain of COVID-19. But we should be equally encouraged by our scientists’ and the country’s commitment to balancing swift action against evidence-based results, which unfortunately takes time to unravel.
With this mindset, let’s take a moment to reflect on what we now know about COVID-19 in February 2021 that we didn’t know six or eight months ago through this evidence-based lens:
1. The 501Y.V2 variant of SARS-CoV-2, causing COVID-19, was detected in the Eastern Cape in November 2020. It accounts for 95% of infections in South Africa today. It’s more transmissible than its predecessor, the original SARS-CoV-2 virus. (High-level evidence.)
2. The Oxford/AstraZeneca vaccine showed 70% efficacy against the original strain. A high standard trial showed only 22% effectiveness against the variant. This was for mild and moderate illness only though. (Level 1 – RCT on young, healthy people). (High-level evidence.)
3. The Oxford/AstraZeneca vaccine’s efficacy against severe disease in South Africa is still unknown and being determined. (High-level evidence.)
4. The Johnson & Johnson vaccine, which is a single-dose vaccine, showed a 82% efficacy against the original strain. This dropped against the variant to 57%, but the number remains high against preventing serious disease, hospitalisation, and death, even against the variant – 83%. This is very important. (High-level evidence.)
5. Pfizer, Moderna, and Sputnik vaccines may achieve similar results against the variant. No trials have been released on them yet.
6. All these vaccines are safe. The question remains which are effective in the South African context. (High-level evidence.)
7. The second wave in South Africa is almost over. The R value is 0.43 at the moment. This means we are in a recovery phase. This is the lowest the R value has been since the pandemic began. (Middle-level evidence.)
8. A third wave is probable – soon. As early as April – June. This is probably inevitable. (Low-level evidence – expert opinion.)
9. The extent of the third wave is determinable by preventative, non-pharmacological behaviour. (High-level evidence.) Masks and social distancing are definitely here to stay for the next year at least. (Expert opinion – low-level evidence.)
10. COVID-19 can be contracted twice – particularly with different variants being present. (High-level evidence.)
11. COVID-19 is likely to last for the rest of our lives and become endemic. However, with the correct vaccination, its clinical effects can be attenuated and it will hopefully tend towards a more common cold. (Low-level evidence. Expert opinion.)
Let’s take a feather out of our South African scientists’ hat, salute our government for its transparency and its approach to following the science, and put up with the unexpected hurdles along the way.