Dr. Irving Kent Loh
In this third summer of COVID, when pandemic fatigue has overwhelmed most of us, except for those who still think this virus is a manufactured figment of George Soros, Bill Gates, and Hillary Clinton, we still yearn for that elusive light at the end of this seemingly inevitable tunnel. With the early iterations of SARS-CoV-2, the amazingly rapid development of incredibly effective mRNA vaccines seemed to tip the battle in humanity’s favor and victory seemed near.
But then biology happened. Or more precisely, the laws of evolution prevailed. As I have written about many times previously, with each reproductive generation, the virus tinkered with its genetic code to find a workaround to the spike protein targets on which the mRNA vaccines had focused in order to interfere with the virus’ ability to infect our vulnerable cells and provide the opportunity to reproduce, which is the prime directive of life. Changes in the viral genome altered the spike protein sufficiently so that the mRNA vaccines began losing their efficacy, combined with the waning of the windows of vaccine or infection-induced protection, allowed variants of concern to emerge to infect humans who lacked the immunologic protection to defending themselves against infection (but protection against serious disease and mortality seems to endure).
Thus emerged Delta, then Omicron, and the subtypes BA.4, and now the most infectious of all, the BA.5 and BA 2.75 variants. Fortunately, evolution favors infectivity, not lethality, so we have thus far not seen spikes in mortality though increases in hospitalizations have occurred. As the editorial board of The Star noted last week, Ventura County has become a hot zone, though you would be hard pressed to believe it when walking around our maskless and crowded population. The virus, as a life form, loves that.
So, assuming the virus continues to evolve, and enough humans continue to ignore the lessons of epidemiology, this scenario has the makings of an infinite (and very depressing) loop. Indeed, it is painful to admit, but it seems that the natural eradication of SARS-CoV-2 virus is less and less likely. Assuming that prayer circles, intelligent design, stashes of hydroxychloroquine, and blaming others may not be sufficient responses, what is the strategy for the rest of us?
It would seem that scientists need to optimize the immunologic rationale for the creation of future vaccines or other enhancers of durable immune responses against the inevitable evolution of future viral variants of concern. As miraculous as the mRNA vaccines have been in targeting spike proteins, their use implies that humans will be constantly playing catch-up with the evolving virus, rather than heading it off. Rather than targeting the coronavirus spike protein, which was the obvious and low-hanging target of our earliest mRNA vaccines, we will need to look at polyvalent or pan-coronavirus strategies.
Let me break that down a bit. Our vaccine scientists have many technologies in their armamentarium beyond classic vaccinology, involving RNA, DNA, recombinant protein, novel adjuvants (drug boosters), and delivery systems such as adenovirus or nasal spray pathways. This is a great time for focusing our best and brightest youth to careers serving humanity and not moving money around. But I digress.
There are markers on and in coronaviruses that transcend the current spike protein vaccine targets. The National Institute of Allergy and Infectious Diseases at the National Institutes of Health has made three large awards for pan-coronavirus vaccine strategies. One strategy is immunization with SARS-CoV-2 amino acid nanoparticles with immune boosters. Also, focusing on antigens common to coronavirus ancestors and not the spike protein may provide an immune response more resistant to lineages that would become variants of concern. Others have also developed pan-sarbecovirus (the parent strain from which the COVID virus emerged) vaccines consisting of human immunoglobulin fragments of the receptor-binding domain plus a novel booster which may have the potential of creating immune responses to future mutated variants.
The vaccines later this year may have Omicron crossover components in them, but they’re not the ones I am describing here that will take much longer to develop and evaluate. But when these imminent polyvalent COVID booster vaccines do become available, you should still get them to optimize protection against severe disease complications.
My point is that scientists around the world are not wringing their hands in frustration, but are devoted to working around the clock as they have been since this pandemic, began to share information and work collaboratively to try and control this pathogen. These are the basic scientists, field workers, laboratory technicians, virologists, clinical-scientists, trialists, epidemiologists, public health experts, healthcare system administrators, bio-pharmaceutical scientists and administrators, all of whom touch the product before it gets into the hands of Your doctors and nurses who give it to you, if you want it.
And even if you don’t want it since COVID may be milder than when it first appeared at the end of 2019, being infected still may give you a 5-25% (depending on your demographic and, interestingly, geography) chance of getting long COVID, which you really don’t want if you’ve been paying attention. It’s been reported that getting COVID may trigger flares of other chronic diseases characterized by inflammation.
So sadly, living with COVID may be the new normal. But life can normalize with novel vaccines and embedded behavioral changes. It may be that eventually this coronavirus may continue to infect humans but at a degree of illness more like a common cold.
But that timeline may be measured in decades or longer, if one looks at the viral evolution mutations of those viruses. In the meantime, I strongly recommend wearing high-quality masks in enclosed spaces especially with people you do not know, and testing if symptomatic but especially before visiting friends or relatives at high risk.
Irving Kent Loh, MD, is a preventive cardiologist and the director of the Ventura Heart Institute in Thousand Oaks. Email him at [email protected]