AAs the virus accelerates its evolution, people are capitulating. For two and a half years, Covid-19 has overtaken our response, becoming increasingly transmissible and reaching levels of infectivity few pathogens have ever reached. Instead of taking an attitude of getting ahead of the virus and outwitting it, people have succumbed.
In recent months we have seen a remarkable increase in transmissibility as the Omicron (BA.1) variant became dominant, with at least a three-fold increase in reproductive numbers beyond delta. Despite hopes that this might top out the virus’ ability to spread, we quickly transitioned to a BA.2 wave, with at least one more jump of around 30% transmissibility, and we are now steering towards a dominant subvariant in the United States called BA.2.12.1, which is another 25% more transmissible than BA.2 and already accounts for almost 50% of new cases.
This certainly represents a significant acceleration in the evolution of the virus. Thousands of variants have existed throughout the pandemic, but only five major variants affecting large populations have been given Greek letter designations (alpha, beta, gamma, delta, and omicron). Each of these previous variants had numerous sublineages or mutations that could be considered relatives of the main variant, but had no functional consequences – they did not increase transmissibility or pathogenicity. But with Omicron we have already seen several subvariants with increased infectivity – not just BA.2, BA.2.12.1, but also BA.4 and BA.5 leading to a new wave in South Africa.
As we watch the virus strikingly improve its ability to find new or repeat hosts, you might think this is an urgent call to action. But instead there has been a public perception that the pandemic is over, while at the same time public health officials are pursuing the policy that we must “live with Covid”.
No, we do not have to live with Covid because the Covid we are seeing now is deeply concerning. Although there has been no increase in hospital admissions, they are increasing significantly, with an increase of more than 20% in the United States in the past two weeks. The proportion of vaccinated versus unvaccinated who are hospitalized and die has increased significantly. So have deaths: during the Delta Wave in the United States, vaccinated individuals accounted for 23% of deaths, while that proportion nearly doubled to 42% during the Omicron Wave. Many of these hospitalizations and deaths in vaccinated individuals can be attributed to the lack of a booster dose or to the significant drop in efficacy that occurs four months after a booster dose.
In addition, there is a big misconception that vaccines are stable to protect against serious illness, hospitalizations and death. You are not. When a booster shot was given during the Delta Wave, it fully restored protection against these episodes, up to 95% effectiveness. But for Omicron with a booster (or second booster) the protection was about 80%. While still high, it represents a large four-fold drop (55% vs. 20% lack of effectiveness). Accordingly, confidence that our vaccines directed against the original 2019 strain will provide high protection against serious disease is overblown. No less are the clear signs that the durability of such protection is reduced. All this is related to the pronounced development of the virus and we still lack data on the vaccine’s effectiveness against the BA.2.12.1 variant, which will soon dominate here.
With the prospect of more damaging variants, it’s inscrutable that we’re giving up now. No more money from the state. The only new vaccine in the funnel is an Omicron booster, but since this is based on the BA.1 variant, it might not offer much protection against what we’re seeing now (BA.2.12.1 has reduced cross-immunity) or where The virus will come this summer when this vaccine might be available. We will even face vaccine shortages in the coming months.
Rather than give up, it’s time to double down on innovations that have a high probability of anticipating the further development of the virus and facilitating the end of the pandemic. The first priority is the development of variant-safe nasal vaccines. A nasal spray that induces mucosal immunity would help block transmission, for which we now have minimal protection from the Omicron hypertransmissible variant family. Three of these nasal vaccines are in late-stage clinical trials, but unlike the vaccines, there has been no Operation Warp Speed or government support to speed up their implementation or success. The next step is to accelerate those clinical trials with so many promising drug candidates. Remember, Paxlovid is the fastest small molecule (pill) program in history – less than two years from design of the molecule to completion of final randomized trials showing high efficacy and its commercialization. Why has so many other antivirals, including pills, inhaled nanobodies and ACE-2 decoys, not been pursued so aggressively?
The concept of a pan-β-coronavirus or pan-sarbecovirus vaccine is enticing and has been pursued by academic laboratories around the world for the last two years. Dozens of broadly neutralizing antibodies (bnAbs) have been discovered that have a high probability of protecting against any future variant. But there is almost no gap to develop and test a vaccine based on these bnAbs. Such vaccines are clearly within our reach, but the lack of investment in a high-priority, high-speed initiative is holding us back. A combination of nasal or oral vaccines, more and better drugs, and a variant-safe coronavirus vaccine would likely bring about a definitive exit from the pandemic.
The public perception that our vaccines are “leaking” is correct, but it is wrong to blame the failure on the vaccines that have saved millions of lives around the world. The accelerated evolution of the virus – that it is sneaky – and has become more and more dangerous over time is at the root of our problem today. We can outsmart the virus and finally overtake it if we don’t submit to weariness instead of rugged endurance and stupidity instead of intelligence.
