AstraZeneca

As we head into what might – or might not – be a perilous winter, it would be nice to have the answer to some vaccine questions: depending on how long ago you had yours, how protected against Covid-19 are you right now? Has your vaccine waned in its effectiveness? What if you had Covid at some point this year? Are you better off having had one brand of vaccine versus another? And how much do you need a booster shot? These are difficult questions to answer. As case numbers go up and down, as people’s behaviour changes, and as natural immunity levels rise, it becomes increasingly messy to draw conclusions. Different groups of people were offered different vaccines as the rollout went on, adding a potential confounder into any analysis. And let’s not forget the different variants: studies have to ask whether any decline in protection is due to the vaccine actually waning, or the older virus being replaced with the more dangerous Delta variant (in that case, the waning presumably wouldn’t continue if no new variants of concern appear). How much does vaccine efficacy actually decline? On 23 October, a paper appeared in preprint (that is, not yet peer-reviewed) form. It reported an analysis of every single severe Covid case in Scotland since the introduction of vaccines in December. That “severe” part is important – in this study we’re talking about people who ended up in intensive care or who died due to the virus. There’s good news and bad news. Vaccines’ efficacy did seem to decline – whether that was due to the appearance of the Delta variant or for other reasons. A double-vaxxed person, who had 92 per cent protection against severe Covid no matter which vaccine they received, saw that protection decrease steadily in approximately the first ten weeks (nearly two-and-a-half months) after the second dose. The good news is that the mRNA vaccines – Pfizer and Moderna – only declined slightly, and seemed to stabilise after that point: they levelled out at about 90 per cent efficacy against severe disease after 20 weeks. Alas, in this study at least, the AstraZeneca vaccine kept reducing in its efficacy: by 20 weeks, its protection against severe disease was as low as 60 per cent. What about the longer term? Does AstraZeneca just wane and wane to absolute zero? Or does its efficacy drop for a while and then level out like the mRNA vaccines? The authors did some extrapolation: they produced models of what their data predicted would happen in future. This is educated guesswork, but nevertheless: one of their models implied AstraZeneca would keep declining to the point that, by 30 weeks (almost seven months), people who got it would have essentially no difference in risk from someone who hadn’t been vaccinated at all. This seems unlikely to be true, but the fact that the data even points in this direction should make us concerned about the AstraZeneca shot in the long term. It suggests an obvious policy: give booster shots as soon as possible to those who have had AstraZeneca, but not necessarily Pfizer or Moderna. And that’s what the scientists argued in their paper. Do I need a booster vaccine? That Scottish study looked at severe disease – but Covid short of hospitalisation is hardly fun in a great many cases. Frustratingly, the best study (also still a non-reviewed preprint) of the effectiveness of mRNA versus AstraZeneca for infection in general, rather than severe disease, only goes up to 16 weeks – just before the severe disease study started seeing substantial differences in the waning trajectories of the vaccine types. But that study does show a waning effect for both Pfizer and AstraZeneca in terms of reducing infection. You can see why there’s been hand-wringing about booster shots. If we want to contain Covid, we want to exceed the herd immunity threshold and ensure everyone has the highest degree of protection. We know that, for Pfizer at least, a booster dose increases the protection again, to over 95 per cent. But a stable 90 per cent is pretty good going: boosters don’t seem anywhere near as crucial for those who’ve had mRNA vaccines. For AstraZeneca vaccines, though, the boosters are much more urgent. Although booster shots in the UK don’t currently discriminate by the original vaccine type, perhaps they should: the encouragement to come along for your third shot should perhaps be targeted more strongly at those who had the less effective, faster-waning vaccine. Do I need a vaccine if I’ve already had Covid? Is natural immunity better? It doesn’t help that the natural immunity issue has become politically polarised, especially in the US. In Israel, one paper (again, not yet peer-reviewed) caused a stir by arguing that natural immunity was both longer-lasting and stronger than that induced by the Pfizer vaccine. But that is inconsistent with other research – including a Public Health England preprint from February and a UK Office for National Statistics report from last week (18 October) – that implies the immunity levels from prior infection are worse, or about the same, as those from vaccination. At the moment it’s hard to draw strong conclusions about natural immunity – it’s unclear why the studies vary so much. But there’s an odd circularity in the “natural immunity over vaccines” argument: to get the protection natural immunity provides, you have to have already had the disease you want to be protected against – with all the risks that entails. Let’s return to our questions from the start. Your vaccine is probably less effective than it was when you first got it, especially if you had it before Delta became the dominant variant. If you had an mRNA vaccine a few months ago, it seems you have a lower, but fairly constant level of protection. If you had AstraZeneca, though, the models suggest you should apply for your booster shot sooner rather than later. [See also: Would the British public support another Covid-19 lockdown?]