I think it's entirely predictable that we are seeing new variants, in fact there are many more around than what we see reported, we only see reports when one variant starts to be seen more frequently. Identified genetic changes don't tell us very much really, they happen all the time, particularly in RNA viruses & most of these will either be damaging to the virus or largely irrelevant. Even the identified changes in the genome that affect the structure of the spike protein may not cause predictable changes. The concern that the Pirola variant may have advantages in gaining cell entry don't seem likely, none of the Omicron variants appear to have any difficulty with this, in some cases the incubation period between exposure and symptom onset can be 1-2 days, that's fast.
I will also say that these studies on the risk of severe outcomes with different vaccine doses are less than helpful, in fact the lancet article might as well have been written in Russian, and I don't speak Russian. They seem to have forgotten to mention the study population of roughly 64 million, and I couldn't find any overall hazard ratio. They also fail to make what they mean by undervaccinated, the guidelines at the time specified different numbers of vaccinations for different age groups. At the time of the study to be fully vaccinated was to have received two with the third considered a booster dose. A second booster became available for most people in September of 2022, after this study.
I suspect attempting to provide some sort of general estimate of risk, when we consider the range of significant variables, was a rater pointless exercise. I've provided a link to a rather less opaque study that looks at similar issues after the 2nd booster, naturally they use different cut off points, so comparisons are useless. It does however make some interesting points, the first is that even after the 2nd booster, when compared to people under 50, those over 80 were 10.43 times more likely to experience severe outcomes. The study also demonstrated the effects of the time between vaccinations, which is increasingly identified as important. People receiving the booster after a period of less than 24 weeks from a previous vaccination were actually at increased risk, I've seen it suggested that a vaccination given too soon can actually damage the immune status. Finally, they report the effects of BMI on risk suggesting
For BMI, we found that those classified as underweight (BMI<18.5) were at greater risk of a severe outcome
than those classified as overweight (BMI 25.0–29.9). Additionally, those classified as a healthy weight (BMI 18.5–24.9) were 1.36(1.25–1.48) times more likely to experience a severe outcome than those classified as overweight. This seems to match the findings of Fragal on BMI and mortality, perhaps you need some stored calories to survive in intensive care. Obesity is still a significant risk.
https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00235-1/fulltext
