In the end, it is perhaps not as simple as the vaccination rate being a pure predictor of mortality for either the influenza or COVID‑19. In the insurance industry, other factors have been major determinants, from socioeconomics and underwriting to age distribution.
Nonetheless, we remain hopeful about preventing Spanish flu‑level deaths through better treatment and mooting infections and reinfections by keeping up with vaccine efficacy. The pharmaceutical industry will remain in the limelight for several years to come as it attempts to reduce the impact of the endemic situation on our lives.
Clinical differences behind vaccine efficacy
Seasonal flu has existed for a long time, is endemic, and yet continues to be unpredictable. One key difference with SARS‑CoV‑2 is that influenza, in theory, may have more mutation possibilities. As an RNA virus, SARS‑CoV‑2 has a spike protein which latches to a single ACE receptor, and with a “proofreading mechanism” is expected to sustain a relatively low mutation rate compared with influenza.22 Future mutations are unknown, and much is still unknown about the Omicron variant. Omicron may be more transmissible, and we are eager to understand how the IFR and introduced reinfection or breakthrough are affected, but part of the panic is the significant number of mutations – 10 times more mutations on the spike protein than compared with Delta against the wild type.25 However, mutations are made possible by a large pool to mutate from: the higher the case rate, arguably the stronger the possibility. In the meantime, while we may have many years living with a new coronavirus ahead of us, vaccines will continue to dampen transmission to some extent.
Current evidence indicates that existing vaccines, while having reduced protection against emerging variants, are still protective against severe illness. So, while we have seen a number of mutations, it is unlikely they will proliferate to the extent that vaccines will require guesswork as to whether they match the season’s particular strain, and where there are drastic drops in their efficacy against severe illness.
These days, there are three or more main strains, and many substrains, of influenza, taking a committee of biological experts to select the strains to target for the annual vaccine.26 So while frequent SARS‑CoV‑2 booster shots – perhaps coupled with an annual flu shot, as many medical experts envision – may be needed to maintain protection and to keep up with mutations, it may not merge in the near future into the vaccine hit-and-miss pattern observed with seasonal flu. U.S. data from the CDC shows high variability of influenza vaccine efficacy by year – from under 20% to over 60%.27 Mutations of COVID‑19 so far have not introduced dips in the mRNA vaccine’s ability to prevent hospitalizations or deaths to levels close to these CDC efficacy observations. Perhaps this is one reason for low penetration of flu vaccination which is well short of WHO guidelines for ages above 65; the public simply thinks of the flu shot as hit and miss. On the other hand, recency may drive vaccine take‑up and indeed there are anecdotes of higher flu shot administration in 2020. Thinking optimistically, perhaps both COVID‑19 and influenza vaccine habits may remain higher and increase respectively – especially if they are administered together as one in future, as envisaged. However, one could foresee reversion to historical vaccination rates for the flu, which would have made for a catastrophic 2021 and possibly 2022 in Germany had the COVID‑19 vaccination rate been at 40% instead of 70%.
Mid-term mortality impacts: What does endemic mean in practice?
This article explores a virus which has been with us for much longer than SARS‑CoV‑2 to provide a backdrop as we consider what it means for an additional set of viruses to become endemic. Surely the sustained impact from direct COVID‑19 mortality will not translate so simply as an additional seasonal flu wave; for mortality modelling, one would need to consider a range of calibrations, some of which have been explored above. One big unknown that remains is whether the IFR of COVID‑19 among the unvaccinated will remain stable. It has risen with Delta from the original strain, yet many experts have reason to believe initial strains mature into less virulent ones in a steady state. One theory of where the 1918 Spanish flu “went” is that, rather than through the use of a magic wand or achieving lasting herd immunity without re‑infection, it simply morphed into a considerably less virulent seasonal flu.28
Ultimately, the analogy with the seasonal flu is also a behavioral one – are public conceptions about seasonal flu a bellwether? Mask wearing and suppression measures for the seasonal flu have historically been absent, apart from in pockets of Asia. Will suppression measures and self-restraint be sustainable with COVID‑19? Statistically, the analogy is a question of how to adjust the R0. This comes down to a question of mutations and behavior. The observed Rt of the same variant in China is presumably lower than in the Netherlands among the unvaccinated and susceptible population and may continue as such in the near future.
Beyond the endemic nature of COVID‑19 itself, many other factors influence all‑cause mortality impact due to secondary impacts from the pandemic. There are reasons for short-term pessimism; for example delayed medical treatments and missed diagnoses of cancer and other progressive diseases contributing to unrelated mortality. On the other hand, there are reasons for optimism with the considerable medical breakthroughs arising during the pandemic, and the possibilities of mRNA technologies. Additional green shoots may be the partial crowd out of other diseases, given the considerable comorbidities associated with COVID‑19 outcomes, and indeed the overlapped mortality with the seasonal flu.
With many thanks to Hanna Speller and Yutaro Kameda for their respective analytical contributions.