Scary 22% vaccine effectiveness in South Africa comes with many caveats

Disappointing preliminary data on AstraZeneca’s COVID-19 vaccine in South Africa – where the coronavirus variant B.1.351 / 501Y.V2 is spreading widely – is leading the government to rethink its vaccination rollout and have raised new concerns at the international level regarding the variant.

But the small study has so many limitations and caveats that experts warn it’s hard to draw conclusions.

The study, which was not published or peer-reviewed but presented at a press conference on Sunday, began in June and recruited only about 2,000 participants, of whom about half received a placebo . At the start of the study – before the emergence of B.1.351 – the vaccine appeared to be over 70% effective in preventing mild to moderate cases of COVID-19. This is largely in line with the conclusion of an international Phase III trial published by AstraZeneca and the University of Oxford vaccine co-developer, which showed mixed results for the replication-deficient adenovirus vaccine. , but an overall efficiency of about 70 percent.

But towards the end of the year – when B.1.351 cases started to take off – South Africa’s results changed dramatically. The vaccine’s overall effectiveness has fallen to just 22% against mild to moderate COVID-19. In an analysis comparing efficacy only in cases known to be due to B.1.351, the vaccine did even worse, showing catastrophic efficacy of just 10 percent.

At first glance, these figures are surprising and suggest that the B.1.351 variant made the otherwise effective vaccine almost useless. But, on closer inspection, these numbers are almost uninterpretable. The trial was simply too small to produce statistically sound results. So every efficiency calculation has huge confidence intervals. For example, the final vaccine efficacy of 22% – based on a total of 42 coronavirus infections in the trial – had a plausible range of estimation between -50% effective and 60% effective.

Persistent questions

The study was also not designed to answer the crucial question of whether the vaccine can prevent serious illness, hospitalization and death. Those enrolled in the trial were relatively young – median age 31 – with very low rates of underlying conditions. These two factors make people much less likely to develop severe COVID-19 and die from the disease.

Experts emphasize that preventing serious illness and death is the most crucial goal of vaccines – not preventing transmission or mild illness. Last month, Johnson & Johnson announced that their vaccine – which is an adenovirus-based vaccine like AstraZeneca’s – was only 57% effective against moderate and severe COVID-19 in South Africa . But, experts applauded the finding that it was 85% effective in preventing serious illness and death. And the company reported that no one vaccinated in their Phase III trial ended up hospitalized or died of the disease. Many experts have defended the unauthorized vaccine as a potential new tool to end the pandemic.

The critical question that looms now is whether AstraZeneca’s vaccine will also protect against serious illness and death in cases involving B.1.351, which has now been detected in more than 30 countries. Amid the uncertainty, South African researchers and officials said on Sunday they would, for now, suspend the deployment of AstraZeneca’s vaccine, which was approved for use in the European Union on 29 January (it has not yet been submitted to the United States). Food and Drug Administration for clearance.) South Africa had recently started offering it to healthcare workers. Instead, officials are now looking at the possibility of a phased deployment, which could involve only vaccinating 100,000 people and monitoring them for a period of time to look at hospitalization rates. If the vaccine seems effective at this point, then they will deploy it further.

“Simply put, we don’t want to end up in a situation where we have vaccinated a million people or two million people with a vaccine that might not be effective in preventing hospitalization and serious illness,” Salim Abdool Karim , co-chair of the South African Ministerial Advisory Committee on COVID-19, said at a press conference on Monday.