by Eric J. Topol
The pandemic is far from over, as evidenced by the rapid rise to global dominance of the JN.1 variant of SARS-CoV-2. This variant is a derivative of BA.2.86, the only other strain that has carried more than 30 new mutations in the spike protein since omicron first came on the scene more than two years ago. This should have warranted designation by the World Health Organization as a variant of concern with a Greek letter, such as pi.
By wastewater levels, JN.1 is now associated with the second-biggest wave of infections in the United States in the pandemic, after omicron. We have lost the ability to track the actual number of infections since most people either test at home or don’t even test at all, but the very high wastewater levels of the virus indicate about 2 million Americans are getting infected each day.
In several countries in Europe, wastewater levels reached unprecedented levels, exceeding omicron. Clearly this virus variant, with its plethora of new mutations, has continued its evolution with mutations adapted for infecting or reinfecting us.
There is, however, some good news about this big wave of infections. It has not resulted in the surge of hospital admissions seen with omicron. The “updated” booster (based on the XBB.1.5 variant that rose to dominance in the U.S. in February), available here since September, has some cross-reactivity with JN.1 in lab studies for inducing neutralizing antibodies to the virus, and a recent Kaiser Permanente report showed the booster provided protection from hospitalization in the range of about 60% against JN.1 and other recently circulating variants.
With the marked differences in the spike protein between XBB.1.5 and JN.1, we are very lucky to see this level of vaccine-induced immune response. Nevertheless, only 19% of eligible Americans have gotten the updated booster. The Kaiser study also showed low levels of protection against hospitalization and emergency room visits for people who had received only prior versions of the vaccine, without the updated booster. That aligns with even more striking differences in the virus sequence of early strains compared with JN.1, and the problem we have with waning immunity four to six months after vaccination.
All of this is occurring on top of the flu and RSV waves, both of which are at very high levels, not clearly having peaked yet, with some people experiencing two of these infections at once.
With all three respiratory viruses circulating at full force, you would think we’d be seeing people wearing masks everywhere in public. That couldn’t be further from the truth. The state of denialism and general refusal to take simple steps to reduce the risk of infection can be seen everywhere.
It has taken health care systems many weeks after JN.1 showed up in October to recognize the threat. Only very recently have some reinstated mask mandates for health care workers and patients. Little has been done across the country to improve indoor air quality, upgrading filtration and ventilation.
Now in its fifth year, SARS-CoV-2 has once again proved to be highly resilient, capable of reinventing itself to infect us. Yet we continue to make-believe that the pandemic is over, that infections have been transformed to common cold status by prior exposure(s), and that life has returned to normal. Sadly, none of this is true.
The massive number of infections in the current wave will undoubtedly lead to more people suffering from long COVID. For a high proportion of people, especially those of advanced age, immunocompromised or with coexisting conditions, getting COVID is nothing close to a straightforward respiratory infection.
What is the exit strategy that could get us to “return to normal”? It certainly can’t happen with the current complacency and false belief that the virus will burn out and go away. Inevitably, there will be another strain in the future that we are not at all prepared for and will lead to yet another very big wave across the planet.
Still, there has been exciting new data on oral, inhaled vaccines that achieve high levels of mucosal immunity and protection against infections, which would be variant proof. The U.S. has invested hundreds of millions of dollars to rev up clinical trials for two different nasal vaccines with promising early clinical trial data, and for improved, variant-proof shots with better protection and durability. But most of these efforts started only recently and are not getting urgent priority for completion during 2024, nothing like what we saw with Operation Warp Speed in 2020.
It’s crickets from the White House on COVID now, with no messaging on getting the updated booster or masking. The Biden administration has done far too little to accelerate research on effective treatments for long COVID.
This passivity reinforces the illusion that the pandemic is behind us when it’s actually raging. And this season will be followed by a more quiescent period, which will, once again, lull us into thinking the pandemic is over. But there is no getting over it until we recognize reality and double down on the research that will allow us to block infections and virus spread, and achieve lasting, variant-proof immunity.
