Thread by @mlipsitch

At the risk of boiling down too much and certainly losing some detail, one way to summarize this wonderful thread is that when we think about vaccine effectiveness, we should think of 4 key variables: 1 which vaccine, 2 age of the person, 3 how long after vax, 4 vs what outcome.

https://twitter.com/celinegounder/status/1417544454223843333

We've been using the simple view that the major vaccines in use in the US/Europe are possibly less effective against infection/symptoms when a variant is involved, but remain highly effective against severe outcomes. Published data so far support this view.

To be more precise, we would say "so far in the general population, up to about 6 months after vaccination, the vaccines have held up against severe outcomes even from Delta, though there is some evidence from Israel, UK, and Canada of declines in effectiveness vs infection."

As more data come out, we should account for these different variables in interpretation. As shown in @celinegounder tweet 64, some measures can go up with time (affinity maturation); tweet 43 shows others go down with time

pausing this thread while I do other things

Oops I should have said 5 things, including the variant in question of course.

There has been much concern about vaccine effectiveness waning, due to levels of important immune effectors declining over time. @celinegounder very importantly (& I haven't seen this said elsewhere) notes that correlates measured just after vaccination may not be key effectors

Still reasonable to assume that some effectors that do matter for protection will decline if we wait long enough post-vaccine, as is the case for many other vaccines.

Variants that are more infectious and/or more readily escape immune responses may pose a greater challenge for protection.

In general the strength of immune response needed to prevent severe outcomes (hospitalization, death) is less than that required to prevent milder outcomes (infection, transmission), and that has been consistent w more decline in effect vs milder outcomes in presence of variants.

Last, older and immunocompromised people start with weaker immune responses.

Putting all this together, the strongest signs of waning protection will likely be in the people vaccinated longest ago, with the least effective vaccines, with the weakest immune responses at baseline, against the milder outcomes.

So the key will be to observe whether the indications of lower effectiveness are consistent with these expectations (in which case a biological explanation is more plausible compared to artifacts of detection) and whether the indications of lower effectiveness...

"trickle up" to the higher levels of severity, where detection of cases is likely more consistent and less dependent on behavior and testing.