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Scary 22% vaccine efficacy in South Africa

comes with heaps of caveats
Beth Mole - 2/8/2021, 8:21 PM
5-6 minutos
Closer look —

South African data on AstraZeneca vaccine is as iffy as it is

scary

Enlarge / Vials in front of the AstraZeneca British biopharmaceutical company logo are seen in this
creative photo taken on 18 November 2020.
Dismal preliminary data on AstraZeneca’s COVID-19 vaccine in South Africa—where the B.1.351/
501Y.V2 coronavirus variant is spreading widely—lead the government there to rethink its
vaccination rollout and raised further international concern about the variant.
But the small study has so many limitations and caveats, experts caution that drawing any
conclusions from it is difficult.
The study, which has not been published or peer-reviewed but presented in a press conference
Sunday, began in June and enrolled only around 2,000 participants, about half of which received a
placebo. Early in the study—before B.1.351 emerged—the vaccine appeared over 70 percent
effective at preventing mild-to-moderate cases of COVID-19. That is largely in line with the
conclusion of an international Phase III trial released by AstraZeneca and vaccine co-developer
Oxford University, which showed mixed results for the replication-deficient adenovirus-based
vaccine but an overall efficacy of around 70 percent.
But toward the end of the year—when cases of B.1.351 began taking off—the South African results
shifted dramatically. The overall efficacy of the vaccine dropped to just 22 percent against mild-to-
moderate COVID-19. In an analysis comparing efficacy solely in cases known to be due to
B.1.351, the vaccine fared even worse, showing an abysmal efficacy of just 10 percent.
On first glance, those numbers are startling, and they suggest that the B.1.351 variant rendered
the otherwise effective vaccine nearly useless. But, with a closer look, those numbers are almost
uninterpretable. The trial was just too small to produce statistically solid results. Thus, each efficacy
calculation has huge confidence intervals. For instance, the vaccine’s ending efficacy of 22 percent
—based on a total of 42 coronavirus infections in the trial—had a plausible estimate range of
between -50 percent effective and 60 percent effective.

Lingering questions
The study also was not designed to answer the critical question of whether the vaccine can prevent
severe disease, hospitalization, and death. The people enrolled in the trial were relatively young—
median age of 31—with very low rates of underlying conditions. Both of those factors make people
far less likely to develop severe COVID-19 and die from the disease.
Experts emphasize that preventing severe disease and death is the most crucial goal of vaccines
—not preventing transmission or mild illnesses. Last month, Johnson & Johnson announced that
its vaccine—which is an adenovirus-based vaccine, like AstraZeneca’s—was only 57 percent
effective against moderate and severe COVID-19 in South Africa. But, experts applauded the
finding that it was 85 percent effective at preventing severe disease and death. And the company
reported that no one vaccinated in its Phase III trial ended up being hospitalized or dying from the
disease. Many experts championed the not-yet-authorized vaccine as a potential new tool for
ending the pandemic.
The critical looming question is now whether AstraZeneca’s vaccine will likewise protect against
severe disease and death in cases involving B.1.351, which has now been detected in more than
30 countries. Given the uncertainty, researchers and officials in South Africa said on Sunday that
they would, for now, pause the rollout of AstraZeneca’s vaccine, which was authorized for use in
the European Union on January 29. (It has not yet been submitted to the US Food and Drug
Administration for authorization.) South Africa had recently begun offering it to healthcare workers.
Instead, officials there are now looking into the possibility of a phased rollout, which might involve
vaccinating just 100,000 people and monitoring them over some time to look at hospitalization
rates. If the vaccine looks effective at that point, they would then roll the vaccine out further.
“Put very simply, we don’t want to end up with a situation where we vaccinated a million people or
two million people with a vaccine that may not be effective in preventing hospitalization and severe
disease,” Salim Abdool Karim, the co-chair of South Africa’s Ministerial Advisory Committee on
COVID-19, said in a press conference Monday.