Chapter 143
Defeating Infectious Agents — 7
But this will not get us to a universal vaccine that protects against all SARS-CoV-2 variants. That’s because the mRNA shots are spike directed, whereas the virus, via natural selection, picks up abundant and diverse spike mutations that enable it to evade our immune response. The pressure from vaccinations on the virus to evolve sets up a vicious loop. Moreover, in an immunocompromised individual, evolution can accelerate in the body, which likely accounts for the hypermutated Omicron and subsequent “Omicron-like” variants with some thirty new spike protein mutations. Updating a new booster to match the variant doesn’t work very well, even with the speed for making updated mRNA vaccines. It takes three months to mass-produce a new booster, and by that time, a different variant typically predominates. Since the SARS-CoV-2 virus has thirty thousand letters, the number of possible variants is essentially infinite. But a vaccine that works against all members of the sarbecovirus or beta-coronavirus family would do the job.
Candidates for a pan-coronavirus “dream” vaccine target other parts of the virus shared by all variants, or they use broad neutralizing antibodies from patients. Such antibodies identify a template for a vaccine that induces their production; in experimental models, these vaccines have been shown to work against diverse beta-coronavirus strains.
However, wouldn’t it make more sense to stop the infection as it enters the body, before it spreads throughout the body? Respiratory viruses enter the body via the lining of our upper airway, invading epithelial cells in the nose and mouth. To provide protection here, we need a nasal spray or inhaled vaccine. Mucosal immunity relies on inducing higher levels of a different antibody (secretory IgA) than shots (IgG); as expected, multiple experimental studies have shown superior protection against infection with nasal vaccines compared with shots.
Beyond the lessons from the vaccines, the pandemic overhauled the way we track pathogens. Rather than only tallying the number of people with infections, hospitalizations, and deaths, we now have adopted new methods that provide precise information that anticipates the virus’s evolutionary path and burden. Genomic sequencing of the virus from people infected tells us about new variants, when and where they appear, and how quickly they are growing in the new cases. We can track the danger specific variants pose, much earlier than in the past.
At the same time, municipal wastewater levels of the virus foretell the future, at the local level, by many days to weeks before seeing the spread of infections. Sequencing the virus excreted in wastewater is also a way to detect new variants once an epidemic has erupted. Neither genomic nor wastewater surveillance were used routinely before COVID-19 hit, but now they not only monitor this virus but also are being used for an increasing array of pathogens including mpox, polio, influenza A and B, RSV, norovirus, and more.
These are vital components of modern pandemic surveillance, but significant improvements lie ahead. We know that many infections are asymptomatic, as we’ve seen with SARS-CoV-2 at least 30 percent—most people are unaware that polio is without symptoms in more than half of people infected. By only tracking people with symptoms, it’s a big miss for the true toll of infections and the paths they take in the population as they spread. Further, the exclusive attention to acute infection events ignores the longer-term sequelae. We know that post-virus syndromes can be enduring and disabling, as seen in tens of millions of people with Long COVID, but they have never been systematically tallied. Pandemic surveillance of the future will be able to give real-time risk assessment at the individual and local levels that incorporates all the relevant metrics on a smartphone app—now possible with multimodal AI. The use of the smartphone to record a forced cough, use AI to make an accurate diagnosis of COVID, and differentiate it from other respiratory pathogens, including tuberculosis, is getting more attention, with results exceeding expectations. If further validated, that could help improve speed and reduce health inequities for diagnosis.