COVID: Insights Gained, Lessons Unheeded

In January 2021 I wrote the first in what became a series of articles in Quadrant on the immunology and treatment of COVID-19. My objective was to give a balanced, science-based understanding of the immunopathology, for those without medical training, of COVID-19 and a critique of treatment options. As a clinical immunologist with 50 years of research into the relationship between infection of the airway and the immune response to it, I felt well placed to contribute to the discussion. My home University had recently awarded me a Doctor of Science and I was informed this was the first such award by that university.

At a time when COVID-19 was more severe, with 20 per cent admitted to hospital and a mortality in excess of 1 per cent, the mantra was “stay at home until you have a significant problem breathing”. This was despite the availability of highly effective, safe repurposed drugs but not approved for COVID even though these medications reduced hospitalisation and mortality by 80 per cent! I flagged concerns in the article regarding efficacy and safety of novel untested genetic “vaccines”. Concerns were based on the principles of mucosal immunology, the systemic distribution of the spike protein (the antigen coded for by the mRNA) that presented a potential for “autoimmune” damage, as well as the emerging idea that the spike protein itself was toxic.

This article will review progress in understanding over the last two years, with comment on success of vaccine roll-out and intervention therapy.

THE PANDEMIC

First, a question: How has the COVID-19 pandemic evolved in Australia over the last three years in relation to world experience?

Through 2020 there were few COVID cases in Australia, about 10-20 new cases a day except for a peak in August-September of up to 1500 infections per day. The mortality rate for most of that year was around 1 per cent, except during the August peak, when it rose to around 5 per cent. This pattern continued through to late 2021.  Coincident with the ending of community lockdowns, the appearance of the new and highly infectious variant, Omicron (but with lower pathogenicity compared to earlier variants), and the onset of the vaccine booster programme, a significant change in pandemic dynamics occurred. Some 80 per cent of all COVID deaths in Australia were recorded over the next 10 months. Reduction in testing and mildness of disease led to gross underestimates of the incidence of infections – making mortality data a more reliable indicator of COVID infection rates, which could be estimated at upwards of 10,000 cases per day during disease peaks in January and August of 2022. Testing blood for antibodies to nucleocapsid antigens, present only in the intact virus, showed that 85-95 per cent of the Australian population had been infected. Forty percent of children with no clinical history of infection have anti-nucleocapsid antibody, reflecting past asymptomatic COVID-19 infection. By mid-February 2023, diagnosed infections had fallen to about 2,500 per day with 35 recorded deaths daily.

How does this compare with the world experience?

Using mortality rates again as an indicator of disease impact, in 2020, when very few deaths were recorded in Australia, the world daily death rates was about 0.8 per million population, increasing through 2021 to approximately 1.5 per million. This differed from Australia, with few deaths, until late 2021. However for the 12 months from November 2021, the average death rate rose to approximately 1.6 per million population, twice that of the average world mortality. From the period of May to December 2022, when daily deaths from COVID-19 in Australia were about 1.5 per million, the world rate had fallen to 0.3 per million.

These statistics indicate that over the course of the pandemic the total number of deaths per million of population in Australia and the world was similar. Was this because geographic and “lockout” isolation effectively reduced early infection rates, with consequent reduction in acquisition of natural immunity (which gives more effective protection than do vaccines)? The high “catch-up” COVID mortality rates in Australia during 2022 may reflect an infectious variant in an immune naive population due to lockdowns. But how could that be as by February 2022 half the population was triple vaccinated? Official NSW figures for COVID-19 in November 2022 showed essentially all hospitalised patients had multiple vaccinations. Together these data question the value of multiple vaccinations through 2022. Experience in the elderly asks a similar question: 80 per cent of the 4,000 pandemic deaths in aged care were in the first nine months of 2022, with a mortality rate of 3.5 per cent. Yet Christopher Knaus of The Guardian (24/9/2022) stated “there was cause for recent optimism—as vaccines are working [and] 84.5% of eligible residents have received their fourth dose”.

To summarise, the course of COVID-19 in the world over three years followed the pattern of influenza pandemics, with significant mortality replaced by highly infectious but less pathogenic variants. For perspective, the total COVID-19 deaths at 6.7 million was about 10 per cent of the 1918 influenza pandemic, and only 50 per cent more than the most recent influenza pandemic in 1968. The Wuhan isolate gave way to the Delta variant which dominated through 2021. Delta was more infectious than the Wuhan variant, while retaining significant pathogenicity. Then came a genetic jump to the Omicron series with significant antigenic drift (point mutations) and, in some variants, shift (where large chunks of genetic material change due to recombination events occurring in host cells infected with more than one variant virus). Omicron variants dominated from early 2022. The significant mutations in the Omicron series led to “antigen escape” from antibodies stimulated by early vaccines. By the time mRNA vaccines were produced to include sequences that covered early Omicron subvariants BA.4 and BA.5, major shifts in antigen were such that sub-variants currently circulating such as XBB 1.5 , (75 per cent of infections) and BQ 1.1 (15 per cent of infections) largely escape vaccine-induced protection and are unaffected by monoclonal antibody therapy that had been developed to protect against earlier variants.

Summary: In Australia few infections and deaths occurred in the first two years, when the original Wuhan strain and then the Delta variant were the dominant pathogens. From the end of 2021 “catch-up” COVID occurred when the less pathogenic Omicron variant dominated, with tens of thousands of cases and upwards of a hundred or so deaths each day, as society and international travel opened. The ballooning of COVID deaths in a highly vaccinated population through mid and late 2022 questions the efficacy of the vaccination strategy.

Returning to the topics covered two years ago, surprisingly little has changed, although, much detail has been added.

1/ Pathogenesis of COVID-19 AND Long COVID

COVID-19 is an infection of the airway and thus subject to the rules of mucosal immunity. A set of mutations enabled a corona virus to escape the mucosal compartment, to enter the gas exchange apparatus of the lungs, thus entering the domain of systemic immunity characterised by IgG antibody. Disease or protection outcomes of infection depend on the balance between antigen (the virus) and antibody: “antigen excess” promotes disease while “antibody excess” promotes protection. The significant difference between mucosal and systemic immunity, is a dominant suppression mediated by T reg cells distributed to mucosal and systemic sites. Models explaining the power of suppression include allergy shots to “turn off” allergic inflammation, and “oral immune tolerance” in mucosal and systemic tissues to explain immune non-responsiveness to food antigens. Inhaled viruses have short term immunity and cause repeated infections. Invariably, these vaccines perform poorly compared to vaccines against systemic infections such as measles.

One surprise discovery in regard to COVID was damage of cell function by spike protein due to a toxic effect on energy production and abnormal folding to form amyloid tissue (the pathology of prion disease and Alzheimer Disease), especially within neural tissue. Damage to the endothelium lining blood vessels and agglutination of red cells causes clots and oxygen desaturation.

Long COVID, an outcome of COVID-19 infection, occurs in about 10 per cent of cases. Risk factors that include more invasive variants, severe disease and subtle immune deficiency suggest persistent virus as a key pathogenic factor.  Initially structural damage following acute infection confused diagnosis, which remains one of exclusion. Core symptoms are fatigue made worse with activity and cognitive impairment commonly described as “brain fog”. Identical symptoms can follow COVID-19 vaccination. Observations that both mRNA coding for spike protein and the spike protein itself can persist in tissues for months, connect persistent infection and vaccine-antigen as putative drivers of a chronic fatigue syndrome due to defective immune clearance. How does that fit?

Study of a model of impaired performance in elite athletes, representing the “tip of the fatigue iceberg”, may be a model for Long COVID.

Studies in elite swimmers at the Australian Institute of Sport produced interesting results.  First, “fatigue” (or impaired performance) was predicted by subtle defects in mucosal immunity which, in turn, related to their training schedules. Second, impaired  performance in those with immune suppression correlated with excretion of EBV (the virus causing Glandular Fever, which becomes integrated in host DNA, and contained by strong immunity). Third, impaired performance was prevented by changing the training schedule or by anti-viral therapy.

Several disconnected observations “fit” with the idea that persistent COVID-19 virus (or spike protein) and immune dysregulation may underpin Long COVID: the clinical risk factors; T reg-mediated immune suppression; persistent antigen; inflammation markers; appearance of dysregulation indices including IgG4 (an anti-inflammatory antibody) and check point inhibitors such as PD-1 and its ligands (that control T cell activity).

A testable hypothesis for Long COVID is “that persistent spike protein (as intact virus or post mRNA vaccine) due in part to an imperfect immune clearance, drives persistent inflammation with core symptoms of fatigue and impaired cognition”. Studies to test this hypothesis could include high dose ivermectin, or metformin — drugs causing accelerated viral clearance and, in the case of metformin, reduced incidence of Long COVID. Ivermectin blocks spike protein clumping of red cells and could be tested as a candidate to neutralise spike protein toxicity.

2/ Genetic vaccines

These were introduced by January 2021, with claims of 90 per cent protection against clinical infection. These were followed by observational studies claiming significant protection against severe disease, especially in the elderly.

However, concerns were raised regarding claimed efficacy and safety.

Blunted enthusiasm for efficacy was based on lessons learnt from 80 years of experience with vaccines for influenza. Both COVID-19 and influenza vaccines simulate IgG antibody which protects the lungs’ gas-exchange apparatus against severe disease. Injected vaccines have little effect on the mucosal phase of infection and thus on viral transmission. And protective responses were limited by immune suppression that dominates following boosters. High mutation rate in influenza RNA requires constant adjustment of vaccine formulation to cover contemporary antigens. In COVID-19 management neither vaccination nor monoclonal antibodies have kept up with antigen variations, noticeably recent subvariants such as XBB 1.5. Major genetic change is due to recombination of large chunks of genetic material between two viruses infecting the same cell. A similar trend occurred with natural antibody decline of protection. Less efficient vaccines risk selection of resistant COVID-19 variants with unpredictable outcomes.

The examples discussed above of allergy shots and oral tolerance predict similar downregulation following poorly considered vaccine strategy. Booster injections provide a temporary increase in protection of 30-40 per cent but are followed in a couple of months by “negative immunity” with more frequent and more severe infections. The change in COVID dynamics in Australia at the end of 2021 was a perfect storm of reduced community lockdowns, a new viral variant not well covered by existing vaccines, and the introduction of the vaccine-booster rollout. By November of 2022, patients admitted in NSW hospitals were nearly all triple vaccinated. mRNA vaccines appear more prone to immune suppression as there is no control over the amount, the site or duration of antigen production. Persistent antigen and mRNA following vaccination are documented. Immunity is a finely balanced response, which includes antigen excess downregulating antibody production.

Safety must always be the predominant consideration associated with vaccine administration: “First do no Harm”. Red flags have been raised around the world with the rollout of genetic vaccines on a “trust-me” basis. 96% of Australians have had at least two doses, with 72 per cent having a booster and facing a fourth or fifth dose. Nearly two million children have two doses of vaccine.

The question never answered is why there is need for an unprecedented 4 to 5 vaccinations over just two years when airway infections have never responded well to vaccines? COVID antigen variation constantly outstrips vaccine adaptation and response is dominated by downregulation that increases following multiple injections. The severe adverse event profile associated with mRNA vaccines includes anaphylaxis, systemic tissue damage due to toxic spike protein and/or immune response to spike protein expressed on cells throughout the body (much as in autoimmune disease) and longer term and transgenerational outcomes due to transcription of coded information into host DNA.

Anaphylaxis (a life-threatening allergic reaction) occurs with 11 of 1,000,000 injections. It is common to many vaccines and usually easily treated. Further vaccinations are then proscribed. Implications of documented reverse transcription of genetic information from COVID-19 vaccines are unknown; resolution of potential threats is a priority concern. The following discussion focusses on the portfolio of serious adverse events, including death, that are being reported.

Misinformation about adverse events is not new. Claims of fraudulent handling of data from the original Pfizer trials (“The many inconsistencies in the Pfizer approval study”) were surprising only because they were published in “Die Welt” the national German paper. The international mainstream press (under the Trusted News Initiative) resisted reporting data that interferes with the vaccine narrative. Serious adverse events following vaccination are reported in national data bases such as VAERS in the US. Reports of death linked to COVID-19 vaccines is 40 times that of reports for all other vaccines, combined, since 1990 (with underreporting recognised to be 10 to 40-fold).

Argument supporting widespread vaccine-related deaths comes from population studies. Prominent has been recognition of an excess in mortality linked to vaccination programmes in most countries, including Australia. An unexpected and unprecedented spiked increase of 400 per cent in India during a four-month period in 2021 correlated with the vaccine rollout. This contrasted with zero increase in reported deaths during the previous 12 months of the pandemic. There could be other causes. Professor Norman Fenton (London) considered all feasible causes of increased mortality. He analysed world excess mortality data through 2022. He was able to exclude COVID-19 infection, Long COVID, impact of lockdowns and quality of healthcare as potential causes. Between week 12 and 24 of 2022 there was a significant linear correlation with vaccine rollout. Fenton concluded there was a strong signal that vaccine programmes caused a proportion of the excess deaths and that subjects in the higher socio-economic category were most impacted.

Using another approach, Dr Wilson Sy analysed Australian data, using criteria first used by Bradford Hill, to support causality. He concluded that increased mortality correlated with the vaccine programme starting five months previously. Analysis of Medicare data in the US on deaths among those under 80 in 2021, showed markedly different curves over time from vaccination, between influenza and pneumococcal vaccination, and COVID-19. For both influenza and pneumococcal vaccines deaths at around 50 were stable, as expected, if the vaccines did not impact mortality. COVID-19 vaccination was followed by a ten-fold increase in mortality, returning only slowly to the baseline. Closer to home are data from the New Zealand government. Through 2022 to January 2023 for every age group, COVID-19 infection was more frequent and resulted in a higher risk of dying the higher the number of vaccinations.

Post-mortem studies have identified spike protein on the surface of damaged cells, surrounded by an infiltrate of T cells, especially in the heart and brain. In German subjects dying unexpectedly, post-mortem studies found 15 per cent were due to post-vaccine damage. The value of prospective studies was shown in Thai schoolboys, with 2 per cent to 3 per cent having laboratory evidence of cardiac damage following mRNA COVID vaccination. This is in contrast with hospital data recording clinical myocarditis at one in 5,000 to 10,000. Scars from subclinical lesions may initiate ventricular fibrillation if exposed to a surge in adrenaline, perhaps explaining the increased incidence of death of athletes. The link to sub-clinical myocarditis is consistent with recent post-mortem diagnoses of “catecholamine-mediated stress cardiomyopathy”, following vaccination.

EARLY TREATMENT

A serious concern, going to the heart of the doctor-patient relationship and the value of “off-label” treatment, has been the cancellation of safe, effective (and inexpensive) therapy that would have saved Australian lives. With TGA approval, following dubious studies, of molnupiravir and remdesivir, anti-viral agents costing thousands of dollars per course with minimal effect and significant toxicity concerns, doctors assumed drug therapy was no longer a threat to vaccine rollout. This was the first reason given to explain earlier cancellation of ivermectin. Trials of ivermectin trials now number 95 involving 134,500 subjects with over 1,000 authors. What they show is a 62 per cent improvement (P<0.0001) including 45 randomised controlled trials. However, in a provisional announcement the goal posts were moved: “More data is required” said the TGA! To repeat (with a weary shake of the head), “More data is required”!

Ivermectin has dramatically changed COVID-19 outcomes in numerous regions and countries across the world, including Utah Pradesh (India) and areas of South America. The recent demonstration of dramatic reversal of oxygen desaturation following ivermectin use, due to inhibition of red cell clumping as a mechanism of action, brings together an immense supporting data base. The targeted attack on ivermectin at every level is without precedent or logic.

Compared to the two antiviral drugs, Ivermectin has a broader treatment window. It is the only one of the three drugs effective in prophylaxis (82 per cent effective in 20,000 subjects), and the only one without restrictions due to age or medications.

CONCLUSION

COVID-19 has become endemic and a milder disease but remains highly transmissible. Awareness of the limitations of genetic vaccines is apparent, although resistance by authorities to change continues. COVID-19 and influenza vaccines share limitations common to all airway virus infections: limited efficacy, inability to prevent mucosal infection or viral transmission. They do not induce sterilising or herd immunity. Cumulative deaths from COVID-19 in Australia align with world figures. The shift in Australian mortality in 2022 in a highly vaccinated population questioned both vaccination efficacy against new variant virus and the capacity of industry to match antigen change with effective genetic vaccines. Programmes based on repeated vaccination without considered spacing, to avoid net suppression and disease promotion, reflect the dominance of narrative over scientific knowledge. The extraordinary act of registering two relatively ineffective and untested antivirals with many disadvantages, costing over $A1,000 per course, while refusing to accept cheap, effective repurposed drugs, reflects a new reality for medicine in the COVID era where clinical decisions are made outside the traditional doctor-patient relationship.

There are numerous reasons why mRNA vaccines – be they the current COVID-19 vaccines or planned vaccines to be produced from new manufacturing plants in Australia (all new mRNA vaccines will share the potential dangers of systemic antigen synthesis and incorporation of genetic information into host DNA) – should be stopped, investigated, and modified if found wanting, to comply with traditional regulatory standards. There is no evidence that genetic vaccines offer advantage over antigen vaccines.

The two-year Report Card is a simple one: a lot of red flags to be heeded and one green one to be acted upon!