The exotic and highly infectious nature of the currently circulating variants raises questions. New emerging variants are now succeeding each other at a rapid pace (e.g., FL.1.5.1, BA.2.86, EG.5). While they share a phylogenetic relationship, they have become so antigenically distinct from their predecessors that they should no longer be considered mere variants but rather different serotypes.
Mutations, as identified by mutation-spotters and confirmed by molecular epidemiologists, are no longer converging to a well-defined spike (S)-associated domain. It appears that mutations enhancing the virus's intrinsic infectivity are currently thriving and competing with each other. This suggests that the viral evolutionary dynamics are no longer driven by ‘herd’ immune selection pressure on viral infectivity.
In the absence of immune selection pressure on viral infectivity and with highly infectious variants in circulation, variants which incorporated spontaneous mutations conferring an even higher level of intrinsic viral infectivity are now more likely to emerge. This is because the higher the viral infectivity, the more the virus replicates and the more likely it is for variants with even higher infectivity to gain a competitive advantage over existing lineages or less infectious offspring. If not constrained by selective immune pressure, variants with steadily increasing infectivity can lead to higher rates of asymptomatic transmission among COVID-19 vaccinees and compete for dominance.
Because public health authorities do not fully comprehend the dynamics of the population-level immune adaptation at play, they do not consider the current evolution very threatening for several reasons:
Few appear to acknowledge that the spread of more infectious Omicron-derived lineages is resulting in reduced attachment of S variant-nonspecific, non-neutralizing antibodies to a highly conserved antigenic site within the N-terminal domain of S protein (therefore also called ‘polyreactive’, non-neutralizing antibodies; PNNAbs). This site is exposed on the surface of S proteins found on progeny virions that adhere to migrating dendritic cells (DCs) surveying the upper respiratory tract. This diminished binding can result in flawed inhibition of viral trans infection in distal organs and may lead to the cell-to-cell trans fusion of virus-infected host cells (https://www.trialsitenews.com/a/how-has-the-covid-19-mass-vaccination-campaign-made-the-natural-selection-and-rapid-propagation-of-a-highly-virulent-variant-highly-likely-44952cc7).
Trans fusion of SARS-CoV-2-infected cells is indicative of high viral pathogenicity, which can clinically manifest as severe or systemic COVID-19 disease. When the segment of the population exerting suboptimal PNNAb-mediated immune pressure on viral trans infectivity surpasses a specific threshold, the entire population represented by that segment will collectively exert immune selection pressure on this trait. This will inevitably lead to the natural selection and spread of a new variant that combines high viral infectivity with high viral trans infectivity (i.e., enhanced virulence) when infecting a population experiencing such immune selection pressure (i.e., highly COVID-19 vaccinated populations).
So, whereas Omicron resisted the infection-inhibiting activity of neutralizing Abs (NAbs) and redirected population-level immune selection pressure on the infectivity of SARS-CoV-2 to population-level immune selection pressure on trans infectivity of Omicron descendants, a novel (O-glycosylated) variant, which I've termed "Hi-Vi-Cron" as an acronym for "Highly Virulent Omicron descendants," might possess the capability to withstand the trans infection- inhibiting effects of PNNAbs while leveraging these antibodies to amplify viral infectivity (https://www.voiceforscienceandsolidarity.org/scientific-blog/predictions-gvb-on-evolution-c-19-pandemic). This increased viral infectivity, in conjunction with heightened virulence, is likely to lead to hyperacute systemic COVID-19 disease, instead of facilitating the adaptation of the host immune response through immune refocusing (as explained in my recently published book: “The Unescapable Immune Escape Pandemic”; drgeert.com).
Understanding the immunological consequences of mass vaccination during a pandemic of a virus causing acute self-limiting infection (e.g., SARS-CoV-2) is essential. The advent of Omicron signaled the irrevocable loss of the opportunity for the population to develop herd immunity and instead turned mass vaccination into an unprecedented and life-threatening "gain-of-function" experiment with the global population as guinea pigs. Just as Omicron came like a thief in the night, so too will Hi-Vi-Cron surprise society.
Predicting complex biological dynamics requires a rigorous scientific analysis of the fundamental causes of these dynamics and their alignment with forthcoming data and observations, rather than extrapolation from ad hoc data or previous observations. Regarding the ongoing immune escape pandemic, the dominant biological patterns are governed by the evolving dynamics of the virus, molded and remolded by the population-level immune response imprinted by mass vaccination. As these viral evolutionary dynamics were initiated in the wrong direction (the immune response should ideally adjust to the virus, not the other way around!), Nature is now compelled to eliminate all incorrect immune adaptations from the population. This scenario will, however, leave many vaccinated individuals (i.e., those who were vaccinated in ways that made them exclusively reliant on this mistaken immune imprinting) entirely unprotected. I cannot imagine how this would not lead to significantly increased mortality rates before protective herd immunity can be achieved. However, this may only transpire once the rate of excess deaths in vaccinees due to immune suppression or immune-related pathology indirectly resulting from mass vaccination has further increased. (https://www.voiceforscienceandsolidarity.org/scientific-blog/immunological-correlates-of-vaccine-breakthrough-infections-caused-by-sars-cov-2-variants-in-highly-c-xx-vaccinated-populations).
The scenario depicted above represents the only means through which nature can transform the ongoing herd immune selection pressure (on viral virulence) exerted by highly COVID-19 vaccinated populations into a state of optimal, sterilizing herd immunity (primarily conferred by the unvaccinated).
The rise in hospitalization and mortality rates could rapidly strain healthcare and funeral service systems in highly COVID-19 vaccinated countries. I therefore urge all healthy unvaccinated individuals to be prepared to assist in such scenarios, whenever and wherever they may arise.
Geert Vanden Bossche received his DVM from the University of Ghent, Belgium, and his PhD degree in Virology from the University of Hohenheim, Germany. He held adjunct faculty appointments at universities in Belgium and Germany. After his career in Academia, Geert joined several vaccine companies (GSK Biologicals, Novartis Vaccines, Solvay Biologicals) to serve various roles in vaccine R&D as well as in late vaccine development.
Geert then moved on to join the Bill & Melinda Gates Foundation’s Global Health Discovery team in Seattle (USA) as Senior Program Officer; he then worked with the Global Alliance for Vaccines and Immunization (GAVI) in Geneva as Senior Ebola Program Manager. At GAVI he tracked efforts to develop an Ebola vaccine. He also represented GAVI in fora with other partners, including WHO, to review progress on the fight against Ebola and to build plans for global pandemic preparedness.
Back in 2015, Geert scrutinized and questioned the safety of the Ebola vaccine that was used in ring vaccination trials conducted by WHO in Guinea. His critical scientific analysis and report on the data published by WHO in the Lancet in 2015 was sent to all international health and regulatory authorities involved in the Ebola vaccination program. After working for GAVI, Geert joined the German Center for Infection Research in Cologne as Head of the Vaccine Development Office. He is at present primarily serving as a Biotech / Vaccine consultant while also conducting his own research on Natural Killer cell-based vaccines.
Email: info@voiceforscienceandsolidarity.org
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