Pre-Existing Immunity to COV 19 – Marc Girardot of Panda Unpacks Its Evolution
In June, BizNews published an article by Marc Girardot – a strategy consultant and a member of PANDA – in which he thoroughly addressed the question of whether those who have recovered from Covid-19 should get the vaccine. In order to answer this question, Girardot focused on the robustness of natural immunity. In this article, an equally important and powerful follow up, Girardot explores the extent and evolution of our pre-existing immunity to Covid-19. Girardot eloquently shows that before it even existed – human beings were largely immunised against Covid-19 due to cross-immunity. He underpins this assertion with numerous references to studies and research papers, one of which found that 80-98% of blood samples taken throughout the globe had cross-reactive T-cells. In simple terms, this means that 80-98% of the world population likely has a significant degree of pre-existing immunity against SARS-CoV-2, which Girardot argues is an explanation for the overall low fatality rates of Covid-19. Using simple analogies, Girardot addresses the various concerns that surround Covid-19. He compares the pandemic to a wildfire without “dry wood”, stating that ‘this pandemic had no fuel. In other words, people were somehow “immune”, and indeed many were asymptomatic.’ As with his first article, this article is loaded with hyperlinks – each of which provide the source of those facts asserted in the article. Girardot thoroughly looks at Covid-19 infection in children, concluding that “Beyond the psychological harm, it is very plausible that the isolation measures have deprived elderly of their best weapon to fight: the gift of super immunity from their grandchildren.” – Nadya Swart
A novel perspective on a not so novel virus
By Marc Girardot*
Within a few years of Columbus’ landing in America, 95% of native Americans were decimated by viruses imported from Europe: 19 out of 20 American Indians died. Not cohabitating with livestock as intensely as Eurasians had for millenia, Aztecs had not built layers of immune defences against influenza, smallpox or measles. Surprisingly, Spanish conquistadores resisted better in the face of the Indians’ own viruses. Likely protected by the Aztecs’ own herd immunity, the Spaniards were not overwhelmed by massive viral loads contingent with an epidemic in a defenceless community.
If these “Noble Savages” weren’t without sin, the most gruesome of which was child sacrifice – they were without virus, at least European ones: Native Americans were “naive” immunologically. Confronted with European viruses, their immune system was like a new-born child seeing for the first time: it had the hardware, but not yet the appropriate software to fight back. No one being immune, the epidemic “avalanche” was uncontained and unstoppable: everyone cross-contaminating one another repeatedly with higher viral doses. The death toll of the invasion of the Americas ended up being cataclysmic: 2,000 times deadlier than Covid-19!
Since January 2020, WHO, health authorities, academia and mainstream media have been contending that SARS-CoV-2 is a completely novel virus, and that it is particularly lethal. There is no doubt, SARS-CoV-2 can be a nasty virus at the individual level. But, why hasn’t the same cataclysm hit our highly connected “naive” world? Why hasn’t the same vicious circle of repeated high viral load contaminations occurred? Why hasn’t “the fire caught on and consumed this immense quantity of dry wood?”
The only logical answer is that SARS-CoV-2 was absolutely not novel.And therefore everything has been blown out of proportion with some very dire consequences for public health and for public liberties.
Having killed allegedly 0.05% of the world population in 18 months, SARS-CoV-2 is evidently not particularly lethal to the community. A simple comparison with the ravages of the Conquistador viruses suggests that SARS-CoV-2 isn’t novel after all, and that populations were originally largely immune to it from the beginning.
In the following lines, I will debunk with facts, data and reason further fallacies and explain why SARS-CoV-2 was never the monstrous threat pictured by the media, by academia and by health authorities.
Like a Running Wildfire?
Viral epidemics are as hard to model as wildfires. Too many variables can influence the outcomes and the unfolding. What we do know from experience is that when all the conditions are right – plenty of dry wood, scorching sun, strong wind, dry bushes… everything will burn with intensity and there is no stopping it: protected cork-oak forest, green meadows… everything will burn.
According to the media, all the conditions were right for the SARS-CoV-2 “wildfire”: an overcrowded planet, ever growing urbanisation, traveling and interacting like never before, a large ageing population and a ‘novel’ virus.
There is no question that, if indeed we had absolutely no immunity against this virus, all the conditions would have been combined for a catastrophe of epic proportions. An epidemic that would have made the Aztec extinction look anecdotal.
But, as a wildfire without “dry wood”, this pandemic had no fuel. In other words, people were somehow “immune”, and indeed many were asymptomatic.
Three proxies to estimate the COVID fatality rate
Here are a few simple ways to estimate the true mortality of COVID using verifiable data:
- Imagine a detective investigating every single COVID death widely. Singapore – by that metric – is unmatched with 423,570 tests per COVID death.The US, France or Germany respectively have tested 831, 893 and 716 per death. In other words, Singapore has tested 500+ times more than other leading nations, and naturally commands a greater precision in its findings. The estimated fatality rate in Singapore is 0.06%, a serious stick in the ground: 100 times less than the original scaremongering prediction…
- Another interesting piece of information comes from pharmaceutical company Regeneron. Last March, they announced promising results from their antibody treatment clinical trial. Their placebo arms comprising 2,089 untreated infected patients caught my attention because only 4.1% ended up in the hospital. Knowing that “at risk patients” represent a maximum 25% of a population, that 31% of hospitalised patients typically transfer to the ICU, and that today – with decent treatment in the hospital – 19% in the ICU die. The “Regeneron” data points to a US IFR of 0.06% today and 0.12% in 2020, i.e. 15-30 times less than current US case fatality rate.
- In the spring of 2020, I set out to simulate the New York City epidemic. Using only real verifiable and redundant data: temperature reading from Kinsa connected thermometers, asymptomacy levels of caregivers to cancerous children and delivering mothers, NYC mortality growth rates… All these data combined into a number of infected in New York City of 15.5 million (estimate on May 10, 2020). At the time, the official death toll was 15,217! So there is no escaping it: in New York the COVID IFR was ̴0.1%.
Depending on timing, on demographics [see.Chart 2], on treatments, on general public health and on density levels, the infection fatality rate in a general population seems to range between 0.01% and 0.2%, essentially comparable to a mild to robust flu, but then again family doctors get to treat influenza.
A NOT SO NEW VIRUS
So, why is this virus not making everyone sick? Why haven’t we seen the catastrophic predictions, materialise?
Ironically, most researchers are focused on the many viral and immune intricacies of SARS-CoV-2, but essentially, they miss out on taking a more systemic perspective that explains quite simply what has occurred: almost nothing is new with SARS-CoV-2.
Like a water leakage, the sooner stopped the better
Let me try an analogy close to home to describe virus propagation through the body. A viral infection is like a water leak in your home: the bigger the leak (aka viral dose), the larger the damage. If you are lucky enough to have an automated detection system (aka Resident memory immunity), the water supply will be stopped instantly with no damage (aka asymptomatic). If not, the water will continue flowing, adding up, becoming visible enough (aka fever…) for you to realise it and run to cut the water supply. You’ll have a lot of mopping and drying up to do, occasionally leaving stains on the walls and ceilings (aka long COVID). But if you are away, and come back after work, with a very delayed response time (aka immunocompromised), your house might be entirely in ruins. You will need to run everywhere, actively try to save the house from actually being destroyed.
A Typical Unfolding
In reality, the SARS-CoV-2 propagation in the body unfolds with exactly the same process as the flu penetrating the respiratory gateways:
- A viral dose enters the body through the airways, either in one discrete event or possibly multiple successive events.
- The immune system has the capacity to reject it immediately – or not – based on context, on dose level and on immunity status.
- If it can’t reject it, the virus continues to propagate until the immune alert “rings” and triggers a more robust immune arsenal.
- The arsenal – fever, T-cells, antibodies… – then rids the body of all virions and kills every infected cell in the upper respiratory tract, causing minor cellular damage (loss of taste/smell…).
- If the immune alert or the reaction is delayed and/or if the immune reaction is weakened, the virus continues to propagate and grows exponentially, penetrating deeper into the body, conquering and damaging critical organs like the brain, the heart, the lungs…
- When the immune arsenal finally kicks in, the battlefield is no longer in the mouth or the nose, but across the entire body,,.
- T-cells scuttle precious infected cells, causing major damage to vital organs and creating life-threatening inflammation and thrombosis, throughout the body.
- Finally, if the patient survives, the body-battlefield needs to heal where it can, and suffer, occasionally irreparable damage (fibrosis…), a Long Covid, with lifelong consequences.
In other words, minimising the clinical impact of COVID-19 is all about early intervention, either therapeutic or immunological, and also about avoiding high dose contamination as much as possible. That is true of all coronaviruses and of the flu, and any decent doctor knows that.
The Protective Umbrella of Cross-Immunity
Let me articulate how cross-immunity likely translates in the epidemic dynamic. Every year, coronavirus induced colds hit the population essentially based on the duration of the winter weather – how long we lock ourselves inside – and on the density of the population. The more people in a square kilometer, the higher the virus density, the more people are contaminated. The denser the city, the more prominent the “super spreader“ conditions.
Imagine coronaviruses hit roughly 10% of the population every winter season. A 1-year old will have a 10% chance of being immune. A 2-year old will have a 19%, and a 10-year old 65%. A 25-year old would be immunised in 93% of the cases. And this is consistent with the data collected on the field; for example in Kansas where 67% of children had pre-existing antibodies to common colds whereas adults had 93%. [Exhibit 2]
So, if adults had pre-existing immunity, via cross-immunity, why are people still falling sick?
To understand this, one must understand four distinct immune populations and how they play out in different contexts:
- Immunologically Naive – those are essentially children and some teens untouched so far by coronaviruses. They benefit from a very strong innate immunity, but their immune system database is limited.
- Super Immune – those infected by a coronavirus in the 2 years before SARS-CoV-2 benefit from a form of temporary “super immunity”. After an infection, a very strong preemptive immune force develops in the portal of entry of the virus – called tissue resident memory cells. This force impedes renewed infection for roughly 2 years.
- Immune for Life – those infected more than 2 years ago still benefit from a vigorous reactive immunity – but not instantaneous – response. They would generally not be in danger, but the infection can be symptomatic.
- Immune Compromised – either temporarily or permanently, despite a life-long immunity, these individuals have the immune information on how to fight, but either the alert message gets delayed or they end up having a weak immune response. These are the people principally falling seriously ill and dying of COVID-19.
The percentage of each of these four populations will vary considerably depending on the infection rate of the region they live in [see.Chart 3]. The denser the region, the higher the rate of infection and the corresponding protection, notably this 2-year super immunity. If common colds hit 25% of a particular region every year, up to 44% of the population would have super immunity [25%+25%.(1-25%) = 44%] and 97% would have a life long immunity.
This likely explains the extraordinary track record of densely populated areas such as Asia and Africa during this pandemic, more so than NPIs that were often started too late to be effective. A recent serology study from Hyderabad in India showed 54.2% had antibodies against SARS-CoV-2 in January 2020. Given the rapidly waning of antibodies, it’s probable Hyderabad was hit 80% or more, giving its population in the densest areas 86% super immunity, in line with 9 asymptomatic in 10 infected revealed by the study.
Even less dense regions where only 5% of the population catch common colds each year would have a 10% “super immunity” and a 79% “lifelong immunity”. It is very clear that cross-immunity likely prevented a cataclysmic pandemic like the one Native Americans succumbed to by simply dampening the virion doses produced by each infected person. And highest density countries provided a super immunity shield to their eldest citizens more so than in lower density countries explaining the mortality discrepancy between Asian countries and Europe or the US.
In my earnest opinion, scientists finger pointing at children couldn’t be more wrong: kids are precious contributors dampening the consequences of epidemics, and likely play a critical epidemiologic role in providing protection to the elderly. They have been shown not to contribute to family disease. Couples with children are more likely to be asymptomatic than couples without. One study found that “Children were five times more likely to have seroconverted without symptoms compared to adults”. Outrageously, and in contradiction with scientific evidence, kids have been accused of endangering the lives of the very grandparents they cherish.
Recently, a John Hopkins study announced that ZERO healthy kids had died of COVID-19 in the United States. So, if kids are so poisonous, why aren’t they poisoning each other? Why aren’t they poisoning themselves?
The reality is kids have much smaller bodies, so their virus production capacity is naturally smaller. They have far less ACE-2 receptors per cell than adults which hinders the production of virions. On top, children have very effective and vigorous immune systems, extremely reactive which cut short virus propagations. With smaller breathing volume and mild cases, it is quite evident that – despite being proportionately more naive immunologically – they never constituted a threat to the community and most likely not to the elderly. In any case, children are much less a threat than the vast majority of adults. It is also very likely that a higher percentage of kids are “super immune” (see below). Hence, the narrative that children are dangerous is as ridiculous as saying that the main risk on a high traffic road filled with heavy trucks is a small bicycle…
Beyond the psychological harm, it is very plausible that the isolation measures have deprived elderly of their best weapon to fight: the gift of super immunity from their grandchildren. It is quite evident that it is preferable for an elderly to get infected by a grandchild occasionally, than by immunocompromised neighbours constantly bombarding them with heavy load inocula in care homes.
The children were the victims of this pandemic. Not only have our children been grossly mistreated: uselessly gagged for months, deprived of education, of motor development and of indispensable social interactions, but also they’ve been put in grave danger physically, immunologically, and psychologically. One recent study – rapidly retracted – seemed to show children were breathing for months – at a minimum – 3 times the 0.2% CO2 legal limit. In Germany, another study highlighted 53% children reported headaches, 42% malaise and 38% impaired learning from mask-wearing. Facts are that we have abused our kids all for nothing.
The Super Immune
After an infection, in the portals of entry of the virus – mouth, nose, lungs or digestive system – battalions of sentinels – called resident memory cells, both B and T – build up in the tissues and are ready to kill the next infection “in the egg”. They are ideally located to quell the infection in the passage of entry where the virus is most vulnerable. If virions pass through, this first line will inevitably have dampened the impact of a high dose inoculum, like soldiers rejecting siege ladders to limit the numbers of invaders into a castle.
This vigorous instantaneous immunity typically lasts up to 2 years – if not stimulated again. This makes a lot of evolutionary sense as most epidemics last two years. When you’ve just had a war, you keep troops guarding the curtain wall for a while… then after a few years, it’s too many resources allocated versus a waning risk, so you just leave one fellow to ring the alarm, and redirect resources to where they are more needed.
The presence of resident memory T-cells is dependent on one meeting a virus with significant genetic similarities in the 2 years prior to the infection. The denser the place one lives in, the higher the chance one benefits from this super-immunity.
This would be a particularly important mechanism of immunity for anyone immunocompromised – elderly and/or sick – because it is off-the-shelf, there is no delayed reaction. In that respect, in the traditional family model, elderly probably benefited greatly from this permanent protective umbrella acquired through the very low viral shedding of their grandchildren. The low death rate in China points to elderly possibly benefiting in large numbers from that protection. Building resident memory T and B-cells in the respiratory tract is a particularly interesting endpoint for a new class of vaccines: an aerosolised vaccine that could engender the proper immune response to kill the infection early on and stop transmission, as opposed to existing vaccines that have failed to provide “sterilising immunity”.
The cross-immunity safety net
As shown by many studies [Exhibit 1], a very large proportion of the population, essentially almost all the adults, had a significant pre-existing cross-immunity against SARS-CoV-2. As one ages one necessarily has caught a cold, at least once, if not repeatedly.
If not stimulated anew, the resident memory cells recede from the respiratory tract, possibly to leave space for new ones triggered by another seasonal epidemic, or simply as a matter of resource reallocation.
However, sentinel T-cells called “circulating memory T-cells” – imagine roaming guards – are still active. In case of renewed “invasion”, they cannot cope with the enemy just yet, but they can sound the alarm and trigger a sort of “immune conscription” to launch a specific counter attack to a new infection.
Given the more diffuse presence in the blood and the lack of action-ready T and B-cell cohorts, a short delay to sound the alert and build the immune battalions is required, time during which the virus can continue to expand.
If a parent gets a small dose from a child, he/she will likely remain asymptomatic. But a medium dose inoculum will trigger symptoms despite this lifelong immunity. This immunity protects against serious illness as long as the host is healthy. However, it does not guarantee against transmission, nor against symptoms.
Overall, this wide immunity – largely dispersed throughout the community – acts as a safety net, reduces the average viral load transmitted and mitigates the “avalanche” effect experienced by Aztecs.
However, obese individuals might still be at risk because their chronic state of inflammation and higher level of ACE-2 receptors make their bodies more prone to severe COVID.
This type of life-long immunity becomes ineffective when the immune system becomes senescent or compromised. This is also the Achilles heel, of current vaccines which will be dependent on the very same delayed immune arsenal.
Compromised immune systems
If you remember the “water leakage” analogy, immunocompromised are those that are away when the leak occurs (aka Infection), come back late (aka delayed/weak response) and have a very bad situation on their hands (aka severe COVID).
Very old age – as well as certain medical conditions (diabetes…) – can impact the normal unfolding of immune reactions: the response can be significantly delayed, which can have catastrophic consequences when combined with a large initial dose of virions capable of multiplying exponentially for a long period of time [Scheme 4] .
These people’s immune systems have necessarily met a SARS-CoV-2 cousin and/or another during their long lives. But this is no longer enough to protect them. The severe COVID patients have dysfunctional immune systems. And this is at the core of the COVID-19 crisis.
The China conundrum
From the start, many have accused China of lying about their numbers. But one needs to put into perspective the driving forces of the COVID-19 pandemic, immunity, age and obesity, and acknowledge that China has a radically different context. With proportionally 1.9 times less elderly and 5.9 times less obesity, China can be 10 times less susceptible. Add on the benefits of Super Immunity, in a country nearly 7 times denser than the United States where traditional families still exist. It is probable that China had a fatality rate 20 times lower than the US, likely bringing it below the 0.01% fatality rate.
The Inoculated Dose is the Poison
One striking reality of COVID-19 – gone unnoticed – is that overwhelmingly patients die without any active SARS-CoV-2 virion in their bodies. In other words, a healthy individual can deal with everyday doses of SARS-CoV-2 quite mundanely, often without realising he/she was ever infected. Even the “at risk” population fundamentally deals with this virus well: when infected and untreated, 96% never need to be hospitalised according to a clinical trial by Regeneron.
So what do people die of?
Severe Covid patients die of the spread of the initial dose and/or their lack of capacity to contain the expansion and the spread. The higher the number of contaminated cells, the higher the cellular damage, the higher the inflammation and the clotting, and the more critical organs are affected. Just like uncontrolled cancerous cells, infected cells become too numerous for the patient to survive.
The immune system can scale rapidly, nevertheless it has defined limits in its capacity to process, as such the initial dose – or doses – is necessarily a key driver of severity. The more diluted the dose the safer.
Once it is recognised that the virus is airborne, health authorities should act decisively by focusing on the activities and zones where viral production is the most active so as to reduce viral concentrations in the air. This doesn’t require a PhD to understand: if many weak people are grouped together and share high doses with each other, they end up poisoning one another, repeatedly – just like the Aztecs did . Care homes turn into virus production factories releasing massive viral quantities in the ambient air.
Mitigating the Viral Network Effect in Community Care
Like firemen attacking a fire at its hottest point, the focus should always have been on care homes and hospitals. These community care institutions are formidable instances of the power of network effects applied to virus contamination and its devastating consequences.
Care homes accounted directly for 41% of the victims of this pandemic, possibly more. Community care facilities – be it retirement homes or hospitals – likely produce the largest viral quantities within a geographic area, therefore producing the most lethal doses. Simple mathematics: the weakest people given the highest viral load repeatedly, sick the longest, all concentrated in one place, will inevitably shed the greatest amount of virus.
Breaking the toxic network effect is imperative, possibly by temporarily scaling down the care facilities by redistributing geographically the residents: some going back to their families, the most independent ones relocated into hotels. Keeping the virus out of care homes and hospitals.
Defusing the Real Viral Bombs
Given the correlation between dose and mortality, a study logically demonstrated that the closer from the source of the epidemic, the more lethal the virus was. Similar to a bomb blast. In other words, if the virus is airborne and dose correlates with lethality, the virus “production centres” should absolutely be curtailed, the most strategic way to limit casualties is to limit virus production at the source, defusing the viral bomb.
One can easily relate to the importance of disarming the central power of virus production in hospitals and care homes :
- Breaking up the mortal network effect – Care home and hospital sanitation technologies and processes should be upgraded to make sure contaminated air is not shared within the care community, nor with the outside world. The air would need to be constantly filtered and sanitised – like in airplanes – so that cross-contamination is absolutely avoided. Using remote patient monitoring technologies, such as the one trialed by the NHS in 2020, can possibly limit the fatality rate by spatially distributing patients at home, or within their families, and by avoiding snowball effects.
- Let fever play its part – Contrary to what many think, fever is another fantastic legacy of evolution. Early on, at a critical moment when the immune arsenal is unprepared, when T-cells and antibodies are nowhere to be seen, raising the body temperature likely damages virions massively hindering virus propagation and avoiding damage done to healthy cells. Any virion then destroyed is thousands of healthy cells saved and less accrued inflammation later. Studies have shown the epidemiological impact of fever can be critical on the evolution of an epidemic. Early generalised usage of paracetamol probably contributed to much longer infections and consequently a much wider epidemic. In that perspective, paracetamol or other fever-reducing drugs should absolutely not be generalised as it is in certain countries, and should be limited to personal situations where the cost of fever becomes superior to its benefits, at a later stage.
- Harnessing Super-Immunity – Unfortunately, current intramuscular vaccines likely don’t trigger resident memory T and B cells in the point of entry of the virus. Only resident immune cells can react early independently of the delayed immune response. In 2016, a study had already demonstrated that for other coronaviruses. Aerosolised vaccines producing mucosal resident immune cells likely better mimic a natural infection and trigger “Super Immunity” to provide better protection, notably for the elderly. This type of vaccine should be accelerated as one of the safest and most effective measures in the near future, more so than more invasive vaccines.
- Prophylactic treatments – While waiting for novel and safer vaccine technologies to be validated, another way to limit production of virions in the community is through proven prophylactic treatment that limit the access of cells to be infected, such as Ivermectin.