We need a definitive exit from our Covid-19 pandemic. Here’s the roadmap | Eric Topol

The humans capitulate to the virus. For the past two and a half years, Covid-19 has gotten more and more transmissible, reaching a level of infectiousness that few pathogens have ever attained. People have succumbed instead of taking a stance of getting ahead of the virus and outsmarting it.

When the Omicron variant became dominant, we experienced a jump in transmissibility, with at least a threefold increase in reproductive number beyond Delta. Despite the hope that this might be reaching the upper limit of the virus's spreadability, 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 sub.

A major misconception is that the vaccines are holding steady to protect against severe disease, hospitalizations, and deaths. They are not

This surely constitutes an acceleration of the evolution of the virus. There have been thousands of variations, but only five major ones, affecting large populations of people, received Greek letter designation. The previous variant had many sub-lineages that were not related to the main variant, but did not increase transmissibility or pathogenicity. Multiple subvariants with heightened infectiousness have already been seen with Omicron, which is leading to a new wave in South Africa.

You would think that the virus would be an urgent call for action as it improves its ability to find new hosts. 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.

We don't have to live with Covid because the Covid we are seeing is very concerning. Over the past two weeks, hospitalizations in the United States have increased by more than 20%. The proportion of people getting hospitalized and dying as a result of beingvaccinated has increased. During the Delta wave in the United States, 23% of the deaths were accounted for by vaccine recipients, whereas this doubled to 42% during the Omicron wave. Many of the hospitalizations and deaths of people who are vaccine-eligible can be attributed to lack of a booster shot or a substantially waned effectiveness four months after a booster.

There is a misconception that the vaccines will protect against severe disease. They are not. During the Delta wave, a booster was given which fully restored protection against these outcomes. The protection for Omicron was 80%. It's still high, but it's fourfold less effective than 20%. The vaccine that was directed to the original strain from the beginning of the year is protective from severe illness. There are clear signs that the protection is less durable. We don't have any data on vaccine effectiveness against the BA.2.12.1 variant, which will soon be dominant here, because of the marked evolution of the virus.

With the prospect of more noxious variants ahead, it's hard to believe that we're giving up. There is no more funding from the government. The Omicron booster is the only new vaccine in the hopper, but since it is based on the BA.1 variant, it may not provide much protection against what we are seeing now. There will be a shortage of vaccines in the months to come.

Rather than giving up, it is time to double down on innovations

It is time to double down on innovations that have a high likelihood of anticipating the further evolution of the virus and facilitating the end of the Pandemic. The first thing on the list is the development of vaccines that are variant-proof. We have little defense against the Omicron family of variants now that we have mucosal immunity. There has not been any government support to speed up the execution or success of the three late-stage clinical trials of the nasal vaccine. There are many candidate drugs that have promise. Paxlovid is the most rapid small molecule program in history, less than two years from the design of the molecule to the completion of definitive randomized trials showing high efficacy and its commercialization. Why hasn't such aggressive pursuit been applied to many other antivirals?

The death toll in the US is higher than any other country.

Academic labs throughout the world have pursued the idea of a pan-sarbecoviruses vaccine over the past two years. Tens of broad neutralizing antibodies have been discovered, which have a high likelihood of protecting against future variant. There is a lack of a vaccine based on these bnAbs. The lack of investment in a high priority and velocity initiative is holding us back. A combination of vaccines, drugs, and a variant-proof coronaviruses vaccine would likely lead to a definitive exit from the epidemic.

The public perception that our vaccines are leaking is true, but it is not the fault of the vaccines, which have saved millions of lives around the world. The virus has become more formidable over time and is at the root of our problem now. If we don't submit to fatigue instead of rugged perseverance and foolishness, we can outsmart the virus and get ahead of it.