Fri, 26 Feb 2021

Alarming announcements made on Sunday night have cast a dark shadow over South Africa's vaccine rollout plan.

The results of a trial of the Oxford/AstraZeneca vaccine, conducted in South Africa, appear to indicate the vaccine's efficacy may be as low as 10% against the new variant, 501Y.V2, that is prevalent throughout the country.

In response, the government has postponed the planned rollout of the Oxford/AstraZeneca vaccine, marking the first time any country's vaccination programme has been halted over doubts about effectiveness, and dealing a severe blow to South Africa's already flimsy vaccine rollout plan.

Next surge

The one million doses of the AstraZeneca vaccine are, at present, the only vaccines actually in South Africa's possession and, although other vaccines have been procured which have shown far better efficacy against 501Y.V2, those have little prospect of arriving in time to actually take effect before the onset of the next surge of Covid-19 cases which is expected to take place with our change in season.

North America and Europe both showed an inflection point in their trajectory of total cases somewhere around late September and early October, which would correspond to late March and early April in the southern hemisphere.

With Easter Sunday taking place on 4 April we can expect a third wave, driven by the change of weather in combination with a weekend of seeding and super-spreader events, to begin less than two months from now.

READ | Analysis: Variants, vaccines and virology: Are we protected?

Phase 1 of our inoculation programme was always a shaky prospect, consisting as it did of just one vaccine and thus flirting with the risk of precisely the immune-escape scenario we now face, and it was always short of the sheer numbers of doses required to have much effect on population-wide spread of the virus.

However, it did offer the promise of sheltering our healthcare sector from the disease burden of Covid-19 at the onset of the third wave. The apparent failure of the AstraZeneca vaccine and its resulting postponement comes as a devastating blow to workers already taking a severe toll from the secondary epidemics of burnout and exhaustion, and many of whom are suffering from PTSD or the long-term effects of prior Covid-19 infections.

Sunday night's presentation by Professor Shabhir Madhi, who was head of the South African arms of both the AstraZeneca and Novavax trials, reiterated another alarming claim - that prior infection with the older variants of Covid-19 does not confer any resistance to infection with 501Y.V2.

In short, the situation as presented by Professor Madhi is that the third wave is around the corner, the only vaccine we have doesn't work, and people who caught Covid-19 in the first wave are vulnerable again. This is utterly devastating news at face value, but are things really quite as bad as all that? The short answer is not quite, for two reasons.

AstraZeneca vaccine efficacy situation not as dire

Firstly, the AstraZeneca vaccine efficacy situation is most likely less dire than it seems.

This is firstly because of the small effective sample size of the trial. While the total number of participants was over 1 600, the total number of actual infections with the new variant was just 39, 20 in the group given a placebo and 19 in the group given the vaccine.

Such a tiny sample size does not carry with it much confidence at all, and so these results should be balanced against other findings and against reasonable expectations. Other vaccines, including Johnson & Johnson which is of the same type as AstraZeneca, did not show such extreme degrees of immune escape, so it's safe to say that random chance may have played some role in the extremely poor results.

Halting one million doses of the only vaccine we have, based on a sample size of just 39 cases, could be considered a precipitate decision, and it is a certainty that the vaccine will still confer some benefit. Generally speaking, the effectiveness of vaccines in protecting against severe illness appears to be quite considerably higher than their efficacy in preventing infection entirely.

Even in the worst case scenario, this vaccine will still confer some immune advantage.

Even if we were to take the efficacy values at face value, putting aside the contribution of random chance, the efficacy as reported is likely to be understated because of the structure of the study. The 10% figure reported is at just 14 days after the second dose, and it has been shown that the immune response elicited by the AstraZeneca vaccine continues to develop for months after it is administered.

It has also been found that the four-week gap between the first and second doses that was used for this trial confers lower efficacy than dosing protocols with a longer gap between doses.

In other words, while we can say with fair confidence that the AstraZeneca's efficacy against 501Y.V2 is low, the findings of the trial do not support a statement that it does not work. We can also be fairly confident that it will still confer a valuable protective effect to its recipients.

The other alarming claim, that prior infection with "vanilla" Covid-19 confers no resistance to 501Y.V2, is even more suspect.

That claim was based on a finding that ~30% of participants in the South African arm of the Novavax trial tested positive for Covid-19 antibodies in serological tests conducted at the outset of the trial and did not have a lower rate of infection through the trial period than did those who tested negative.

READ | Analysis: Covid in SA: Where we are now, whats next and how two vaccine trials will tell our fate

What this tells us is simply that testing positive for antibodies does not indicate resistance, a fact which has been quite well established already.

At several times in the past, cities or even countries have been claimed to be at, or close to, functional herd immunity based on serological findings and subsequently suffered severe waves of infections. On the other hand, a study tracking infections among UK healthcare workers showed that symptomatic infections, confirmed with PCR tests, conferred strong long-term resistance to subsequent infections.

Immune advantage

The extent to which this resistance extends to the new variant is unclear, but the claim that it is non-existent is not supported by the findings of the Novavax trial. In-vitro tests in which the neutralising activity of serum from past Covid-19 patients has been tested against the new variant have shown quite a large degree of immune escape, but certainly not total immune escape, and such tests only factor in one part of the broad immune response. The overwhelming likelihood is that prior infection with "vanilla" Covid-19 does confer at least some immune advantage against the new variant.

The two defences we have against the winter wave, namely the AstraZeneca vaccine and existing natural immunity, are certainly greatly weakened against the new variant, but it is by no means eliminated completely.

Source: News24

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