Friday, January 20, 2023

The Ongoing Mutation of SARS-CoV-2 & Attempts at Vaccination-based Control


Top scientists investigating the crossroads of genomics, immunology, microbiology, and infectious disease concluded the extreme difficulty of RNA virus immunization in a 2018 research paper titled “Immune Responses to RNA Viruses,” all but cautioning public health agencies’ responses to most RNA viruses and their respective threats to public safety. They wrote that in the aggregate, RNA pathogens, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), Ebola virus, Zika virus, respiratory syncytial virus (RSV), influenza viruses, yellow fever virus, dengue virus, rhinoviruses (common cold), human T-lymphotropic virus type 1 (HTLV-I), poliovirus, and measles virus take hundreds of millions of lives daily worldwide. Published just a year-and-a-half before the outbreak of SARS-CoV-2, the authors acknowledged the current state of science: “that at the present time, no vaccine or specific treatment is available for many of these viruses, and some of the available vaccines and treatments are not highly effective.” So, this is for viruses known to human science for decades in some cases. What about a brand-new pathogen with certain heretofore not seen qualities making the RNA virus far more transmissible? How could government research entities and industry be so confident as to a blockbuster vaccine response that would control the pathogen, leading to herd immunity? After all, this was the initial impetus behind the mass vaccine development as evidenced by underlying drivers to control the virus by achieving a 70% vaccination rate. Well-intentioned to rapidly respond to a deadly pathogen, time is now to critically evaluate options with a willingness to let go of any faulty assumptions.

In Detail:

The human innate immune system represents a key force in sensing RNA viruses and, thus, a considerable influence on the antiviral responses and the pathogenesis of diseases caused by such RNA viruses. Yes, special attention needs to be directed toward the immune response to RNA viruses and SARS-CoV-2. In that 2018 piece, the authors Said et al. introduce an RNA virus, HIF, as an example of the interaction between an RNA virus and the immune system and how such interactions control the pathophysiology of the disease caused by the virus.

While in the COVID-19 response to the novel RNA virus called SARS-CoV-2, health authorities across public agencies and their apex research institutes sought to use an mRNA vaccine developed across the finish line in just about 10 months as a means of mass controlling the pathogen as evidenced by repeated targeting of 70% of vaccination rates by the World Health Organization initially to achieve herd immunity to stop the spread of the pathogen, not just to protect the highest risk populations viral surges with bolstered human antibody responses.

No, early on it was clear that from health authorities to governments and elected officials to the vaccine developers (pharma) that the vaccine was a means of eradicating the viral pathogen from existence. Even with clear evidence by the spring of 2021 that the novel vaccines would not stop viral transmission, intense public campaigns commenced, including announced mandates by POTUS precisely to stop viral spread.

Despite these intensive public health initiatives seeking to control the COVID-19 pandemic, wave after wave of viral mutation, starting first with the Delta variant of concern, followed by a series of Omicron subvariant mutants, the recent entry of the highly infectious, considerably resistant, and intensely immune system-evading XBB.1.5 SARS-CoV-2 subvariant merely represents the latest such pathogen, not something that should be surprising the scientific community at this point, yet the popular press treats it as a novelty.

The latest RNA-based viral mutation comes out of the XBB lineage, which emerged after a natural co-infection of a human host with two key Omicron subvariants, including BA.2.10.1 and BA.2.7 first identified in India several months ago (summer 2022). The “fifth grandchild” of the first XBB variant, it could be the most genetically sophisticated and contagious of the Omicron subvariants to date since the initial advent of this version of SARS-CoV-2 in November 2021.

In circulation in nearly 40 nations, as reported by the World Health Organization (WHO), it’s now dominating in the United States. Importantly, the current vaccine booster (Omicron bivalent BA.4/BA.5) was developed for a version that is on its way toward extinction while this untargeted mutant surges, especially on the east coast. XBB.1.5 will more than likely become the predominant SARS-CoV-2 pathogen, that RNA class of virus that scientists all along have suggested is extremely difficult to stop.

Current SARS-CoV-2 Viral Variants Across the USA
The Centers for Disease Control and Prevention (CDC) report on variant representation and distribution across America.

XBB.1.5 now represents 43% of all SARS-CoV-2 variants in circulation as of January 14, 2023, reports the CDC.

There is limited data about the ability of XBB.1.5 to cause serious illness. According to the World Health Organization, XBB.1.5 does not have any specific mutations that make it any more dangerous than its ancestral subvariants.

Nonetheless, XBB.1.5 is perceived as being equally capable of causing serious illness in elderly and immunocompromised persons compared to previous Omicron subvariants of concern.

It’s not clear how dangerous this particular variant will be as measured by contribution to morbidity and mortality rates, but evidence suggests higher transmission rates yet likely, lower mortality rates.

But while public health messaging continues to declare repeatedly that vaccination is the best means of stopping serious SARS-CoV-2 illness, XBB.1.5 and other variants such as XBB.1 under the Omicron umbrella, represent the pathogens with the most immune-evasive properties as discussed by WHO directly.

Initial laboratory study results didn’t bode well for the prospects of the Omicron bivalent BA.4/BA/5 booster vaccine targeting this latest mutation (XBB.1.5). TrialSite reported that a notable team at University of Texas Medical Branch reported that a group of scientists at the University of Texas Medical Branch (UTMB) in Galveston, Texas reports the mutating Omicron subvariants such as BA.2.75.2, BQ.1.1., and XBB.1 feature additional spike mutations, further inhibiting COVID-19 vaccine booster effectiveness. Led by Pei-Yong Shi, Ph.D., UTMB’s Vice President for Research, co-corresponding authors Ping Re, Ph.D., an epidemiologist, and Xuping Xie, Ph.D., an assistant a professor of biochemistry and molecular biology, the UTMB investigators reported that this particular vaccine now aggressively promoted by the U.S. government failed to generate robust neutralization against the newly emerged BA.2.75.2, BQ.1.1, or XBB.1. At the time (Dec 7), TrialSite reported that unfortunately, BQ.1 and BQ.1.1 represent the fastest growing Omicron subvariants across America.

This media also reported on a study with disturbing results from a large retrospective cohort study sponsored by the Cleveland Clinic, tapping into robust data associated with the hospital’s electronic health records. The data suggests a growing number of SARS-CoV-2 infections associated with number of vaccination boosters. But several confounding factors could influence that outcome.

TrialSite reported on the lab results from Columbia University’s David Ho, revealing declining bivalent BA.4/BA.5 booster performance against XBB.1.5, 155-fold lower than against the wild-type virus after a boost targeting the monovalent strain. See TrialSite’s “Bivalent Bombshell? BA.4/BA.5 mRNA Booster Dose Fails Comparative Antibody Titer Test: Could it be Antigenic Sin?”

Even renowned vaccine expert and FDA Vaccine and Related Biological Products Advisory Committee (VRBPAC) member, Dr. Paul Offit, has gone to the press announcing the current COVID-19 vaccine trajectory has all but failed at this point.

One other recent study result shows concerns such as “T-cell exhaustion” that implies with multiple boosters comes the prospect of externalities with unknown implications, although the study may be underpowered.

So, what degree of protection does the current booster doses offer people against XBB.1.5?
Regardless of point of view, the unfolding science appears clear now that both monovalent and bivalent booster jabs cannot be counted on for sufficient protection against XBB.1.5, yet government scientific agencies’ stance continues to remain to the contrary.

Some state level health officials have moved in the direction of the unfolding science such as in Florida, subjecting all involved to intense public scrutiny and pressure. There in the Sunshine State, given the large percentages of the American population have either been previously vaccinated and/or infected, even the State of Florida’s Surgeon General Joseph Ladapo now recommends against healthy young people getting the COVID-19 vaccine booster. This recommendation, however, goes against CDC, and other major medical associations and societies that remain steadfast that boosting with the latest dose, even if BA.5 is not much in circulation, offers some degree of protection for at least, the handful of cold winter months where populations will be more vulnerable.

Back to the scientific challenges posed with RNA viruses at the onset of this article, any attempt to use vaccination thus far as means of actually controlling the SARS-CoV-2 based pandemic hasn't worked out well. More people have died during the first year of mass vaccination versus the first year of the pandemic, although vaccination does provide a surge of antibodies that does protect people from more serious hospitalization, at least temporarily. But how long remains an open question—part of an unfolding science. As of August 2022, the Washington Post itself reported that the pandemic was no longer one of the “unvaccinated,’ as more deaths involved the vaccinated than the unvaccinated.

Of course, this is explained in part by the fact that about 70% of the American population is fully vaccinated. But this also demonstrates how mutating variants such as XBB.1.5 more easily evade neutralizing antibodies. Assessments of the U.S. [and world] pandemic response are in order. See TrialSite’s founder Daniel O’Connor’s “Pandemic Response 2.0---How Could it be Better: A Review of What We Know.”

We do now that commonsensical measure for protection range from good hygiene practices—such as handwashing, respect of people’s space [distancing], masking--although controversial [at least indoors in public spaces], and if one has an upper respiratory infection, remaining at home and resting and not increasing the probability of spreading the virus to others is a good start.

Existing monoclonal antibodies don’t work well, if at all, against the mutating variants such as XBB.1.5, meaning the ongoing intense evolution of this RNA virus makes it difficult for pharmaceutical products designed against a specific variant of concern. The antiviral Paxlovid offers some protection for some cohorts fitting in the inclusion criteria for the drug although rebound cases are reported.

David Boulware recently reported to TrialSite that metformin appears to have supportive effect against SARS-CoV-2—more so than even fluvoxamine. While TrialSite reported this on the day after Christmas the mass media was strangely silent on this good news. See TrialSite’s “Bramante & Boulware Deliver an Early Christmas Gift: Metformin Lowers Risk of Long COVID.”

Front line physicians independent of health systems have taken matters into their own hands. For example, the controversial but much loved Front Line Covid-19 Critical Care (FLCCC) Alliance, or Dr. Peter McCullough, treats patients with various protocols involving repurposed medicines.

In typical times, licensed physicians and consenting patients can without controversy use off label drugs to treat conditions so long as this is done responsibly with full patient consent, and the like. But during the pandemic, with an unprecedented centralizing of medicinal response, discussing off label regimen such as ivermectin is classified as “misinformation,” and in states like California with its new law in effect, can lead to the loss of licensure for physicians that dare to utter alternative approaches.

Meanwhile, no medicinal products are perfect. Some vaccines may have rare side effects. In the case of the SARS-CoV-2 vaccines, given the magnitude and scale of the pandemic response with 225 million plus fully vaccinated, even a 0.2% serious side effect rate equals nearly half-a-million vaccine-injured persons. Due to intense social pressures doctors and health systems are not recognizing this problem, leading to stigmatization and a lack of care. Groups such as React19 have been formed to represent vaccine injured. They should be properly funded, advocating for the injured as the vaccines were mandated on the population. A much larger long COVID group needs attention and care as well as nations attempt now to transition to an endemic reality.




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