We need a definitive exit from our Covid-19 pandemic. Heres the roadmap – The Guardian

As the virus accelerates its evolution, the humans capitulate. For two and a half years, the virus has been outrunning our response, getting progressively more and more transmissible, reaching a level of infectiousness that few pathogens have ever attained. Instead of taking a stance of getting ahead of the virus, and outsmarting it, people have succumbed.

In recent months, we experienced a striking jump in transmissibility when the Omicron (BA.1) variant became dominant with at least a three-fold increase in reproductive number beyond Delta. Despite the hope that this might be reaching the upper limit of the viruss spread ability, we quickly transitioned to a BA.2 wave with at least another jump of about 30% transmissibility, and now we are heading, in the United States, to a dominant subvariant known as BA.2.12.1, which is another 25% more transmissible than BA.2 and already accounting for close to 50% of new cases.

This surely constitutes a meaningful acceleration of the viruss evolution. There have been thousands of variants over the course of the pandemic, but only 5 major variants, affecting large populations of people, received Greek letter designations (Alpha, Beta, Gamma, Delta, and Omicron). Each of these previous variants had numerous sub-lineages, or mutations that might be considered relatives of the main variant but had no functional consequence they did not increase transmissibility or pathogenicity. But with Omicron, we have already seen multiple subvariants with heightened infectiousness, not just BA.2, BA.2.12.1, but also BA.4 and BA.5 which are leading to a new wave in South Africa.

As we watch the virus strikingly improve its ability to find new or repeat hosts, you would think it would be considered an urgent call for action. But instead, there has been a public perception that the pandemic is over, while, at the same time, public health agencies are adopting the policy that we must live with Covid.

No, we dont have to live with Covid, because the Covid we are seeing now is deeply concerning. While there has not been a surge in hospitalizations, they are clearly on the increase, with more than a 20 per cent rise in the United States over the past 2 weeks. The proportion of people getting hospitalized and dying among the vaccinated, as compared with unvaccinated, has substantially increased. As has the deaths: during the Delta wave in the United States, vaccinated individuals accounted for 23 per cent of the deaths, whereas this nearly doubled to 42% during the Omicron wave. Much of these hospitalizations and deaths among vaccinated people can be attributed to lack of a booster shot or the substantially waned effectiveness that sets in by 4 months after a booster.

Moreover, a major misconception is that the vaccines are holding steady to protect against severe disease, hospitalizations, and deaths. They are not. When a booster was given during the Delta wave, that fully restored protection against these outcomes, to the level of 95% effectiveness. But for Omicron, with a booster (or second booster) the protection was approximately 80 per cent, while still high, it represents a major, 4-fold (lack of effectiveness of 55 vs 20%) dropdown. Accordingly, the confidence that our vaccines, directed to the original strain from 2019, are highly protective from severe illness is exaggerated. No less are the clear signs that their durability of such protection reduced. All of this is tied to the marked evolution of the virus, and we yet lack any data on vaccine effectiveness versus the BA.2.12.1 variant, soon to be dominant here.

With the prospect for more noxious variants that lie ahead, it is unfathomable that we now surrender. No more funding from the government. The only new vaccine in the hopper is an Omicron booster, but since that is based on the BA.1 variant, it may not provide much protection against what we are seeing now (BA.2.12.1 has reduced cross-immunity) or where the virus will be come this summer when that vaccine may become available. We even face a shortage of vaccines in the months ahead.

Rather than giving up, it is time to double down on innovations that have high likelihood of anticipating the further evolution of the virus and facilitating the end of the pandemic. First on the list is the development of nasal vaccines that are variant-proof. A nasal spray that induces mucosal immunity would help to block transmission, for which we have minimal defense now from the hyper-transmissible Omicron family of variants. Three such nasal vaccines are in late-stage clinical trials, but unlike the shots, there has not been any Operation Warp Speed or governmental support to expedite their execution or success. Next, with so many candidate drugs that have promise, is to speed these clinical trials. Recall that Paxlovid as the most rapid small molecule (pill) program in history, less than two years from design of the molecule to the completion of definitive randomized trials showing high efficacy and its commercialization. Why hasnt such aggressive pursuit been applied to so many other antivirals, which include pills, inhaled nanobodies and ACE-2 decoys?

The concept of a pan--coronavirus or pan-sarbecovirus vaccine is alluring and has been pursued by academic labs throughout the world over the past two years, Tens of broad neutralizing antibodies (bnAbs) have been discovered, which have high likelihood of protecting against any future variant. But there is nearly a void of developing and testing a vaccine based on these bnAbs. Such vaccines are clearly in our reach, but the lack of investment in a high priority and velocity initiative is holding us back. A combination of nasal or oral vaccines, more and better drugs, and a variant-proof coronavirus vaccine would likely catalyze a definitive pandemic exit.

The public perception that our vaccines are leaky is true, but its off-base to assign the fault to the vaccines, which have saved millions of lives around the world. It the viruss accelerated evolution that its sneaky and became more formidable over time that is at the root of our problem now. We can outsmart and finally get ahead of the virus if we dont submit to fatigue instead of rugged perseverance and to foolishness rather than intelligence.

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We need a definitive exit from our Covid-19 pandemic. Heres the roadmap - The Guardian