JN.1 is currently evolving into a quasispecies within highly COVID-19 vaccinated populations, providing a fertile breeding ground for a new Coronavirus strain with enhanced virulence.

‘Quasispecies’ refers to a population of numerous closely related variants, characterized by minor mutations in their genetic sequences, coexisting within a host organism. By monitoring mutation spotters on social media, one can learn how JN.1 is now evolving into a 'swarm' of slightly genetically distinct variants, thus forming a typical quasispecies population.

This evolutionary process strongly supports my hypothesis that enhanced cytotoxic T cell lymphocyte (CTL)-mediated nonselective immune pressure on viral transmissibility is currently conferring a fitness advantage to a multitude of JN.1 descendants, owing to their gain of multiple advantageous phenotypic functions (e.g., resistance to neutralizing antibodies, heightened infectiousness, and enhanced viral production capacity)[1]. By establishing a quasispecies population and a state of dynamic equilibrium, marked by continuous competition and selection among different individual variants within the quasispecies, SARS-CoV-2 demonstrates its ability to adapt to the increasing population-level immune pressure on viral transmissibility. Due to the genetic diversity present in its variants, a quasispecies serves as a reservoir of genetic variations enabling the virus to adapt more rapidly to its changing host environment, including host immune pressure on specific phenotypic traits. This expedites the emergence of new viral variants with improved resistance to the hostile environment (i.e., resulting in ‘gain-of-viral function’).

As activated universal CTL responses can only partially reduce viral transmission, they collectively exert nonselective immune pressure on viral inter-host transmissibility within highly Covid-19 (C-19) vaccinated populations. This nonselective immune pressure ultimately leads to the emergence of a diverse array of circulating variants characterized by a combination of mutations that enhance viral productivity¹.

Variants, such as those belonging to the JN.1 clan, which possess the ability to increase their viral production rate without suppressing the secretion of pro-inflammatory ORF8 protein[2]^,[3] gain a competitive advantage by favoring their adsorption on migratory dendritic cells rather than being internalized into antigen-presenting cells (see figure below). Consequently, the spectrum of circulating variants is now expected to increasingly encompass JN.1 descendants. Given the escalating immune pressure on viral transmissibility within highly C-19 vaccinated populations, it is reasonable to anticipate that the composition of circulating variants will eventually converge to a similar JN.1-derived quasispecies in those populations.

Furthermore, the widespread activation of universal CTL responses results in suboptimal concentrations of polyreactive nonneutralizing antibodies (PNNAbs) binding to a variant-nonspecific antigenic site within the N-terminal domain of spike protein (S-NTD)[4]. Suboptimal concentrations of these antibodies are currently leading to highly C-19 vaccinated populations exerting escalating non-selective immune pressure on viral trans infectiousness. This results in a corresponding increase in non-selective immune pressure on viral intra-host transmissibility, which correlates with viral virulence.

As the immune pressure on viral virulence intensifies, any member of the quasispecies harboring mutations facilitating the accommodation of additional, virulence-enhancing glycan chains on mutated O-glycosites could serve as the origin of a new coronavirus (CoV) strain exhibiting enhanced severe disease in highly C-19 vaccinated populations^4,[5]. In essence, the establishment of a quasispecies population by JN.1 likely indicates the virus's readiness to undergo a dramatic structural and functional transformation, thus precipitating the sudden emergence of a new CoV lineage (i.e., HIVICRON[6]) capable of inducing a significant surge in enhanced severe disease across highly C-19 vaccinated populations.

Therefore, I firmly believe that the growing prevalence of chronic, vaccine-associated immune pathology (‘long Covid’) and the dominance of the JN.1 quasispecies signal the onset of the final, hyperacute phase of the C-19 immune escape pandemic. This phase is expected to be characterized by a spectacular surge in enhanced viral virulence caused by the rapid dissemination of HIVICRON throughout all organs of vaccinated individuals.

Last, for those who will be inclined to attribute a severe wave of what they call "disease X" to the out-of-the-blue emergence of this entirely new CoV, I emphasize that any newly emerging CoV subsequent to this immune escape pandemic, particularly one displaying high virulence in highly C-19 vaccinated populations, should be regarded as a delayed outcome of the large-scale C-19 vaccination program. As repeatedly discussed, the latter has merely catalyzed a cascade of diverse viral immune escape events, thus representing an unparalleled ‘gain-of-function’ experiment conducted on the very human species.

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[1] https://www.voiceforscienceandsolidarity.org/scientific-blog/i-can-now-spot-the-tsunami-at-the-horizon

[2] https://www.nature.com/articles/s41467-024-45274-3

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193824/

[4] https://www.voiceforscienceandsolidarity.org/scientific-blog/predictions-gvb-on-evolution-c-19-pandemic

[5] https://www.voiceforscienceandsolidarity.org/scientific-blog/wisdom-from-sherlock-holmes

[6] HI-VI-CRON: A Highly VIrulent CoV strain replacing the entire family of Omicron descendants.

Fig. : Early Omicron descendants enter target host cells via PNNAb-dependent enhancement of infection (1Œ). PNNAbs bind to progeny virus tethered to these DCs, which subsequently migrate to the lungs and other distal organs (2). On the other hand, previously SIR-primed Abs bind with low-affinity to the antigenically more distant immune escape variant, thereby generating  Ab-virus complexes that are taken up into patrolling APCs (Ž3). Enhanced uptake of large Ab-virus complexes into APCs facilitates strong activation of CTLs, thereby enabling the elimination of virus-infected host cells.
Highly infectious Omicron descendants do not rely on PNNAb-dependent enhancement of infection to enter target host cells. Replication of highly infectious variants generates an immunological environment that promotes their adsorption onto tissue-resident DCs. Due to their high level of intrinsic infectiousness, newly emerging, more transmissible Omicron descendants (e.g., members of the JN.1 clan) will therefore enhance the adsorption of progeny virions on migratory DCs and thereby reduce viral uptake by APCs. Reduced viral uptake by APCs will promote the priming of CD4+ T cells. Some of these T cells may be self-reactive, while others are foreign-centered but fail to serve as T helper cells to assist in boosting of previously SIR-primed Abs due to a lack of immune recognition of the corresponding S-associated B cell epitopes comprised within large Ab-coated virus complexes. Diminished boosting of previously primed anti-S Abs results in diminished production of PNNAbs.
As these more infectious and inflammatory variants (i.e., the JN.1 clan) steadily increase in prevalence, diminished production of PNNAbs, combined with their enhanced binding to highly infectious DC-tethered progeny virions leads to a steadily increasing immune pressure on viral virulence in highly C-19 vaccinated populations. This is thought to eventually trigger the selection of a new Coronavirus lineage that has the capacity to cause PNNAb-mediated enhancement of VBTIs in highly C-19-vaccinated populations, thereby causing a massive wave of enhanced severe C-19 disease.