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Pandemic Journal

As Dr Robert Hess expected, the pandemic is becoming more complex

Dr Robert HEss

Dr Robert Hess – 29/07/2021

As Dr Robert Hess expected, the pandemic is becoming more complex and problematic in nature, which makes it all the more difficult to make any firm predictions for the autumn.

In focus: Vaccine side-effects versus post-acute sequelae (“Long Covid”).

The forecast of Dr Robert Hess in the spring of 2021 that the pandemic would take off in a more complex and problematic direction ran contrary to general opinion. It is now being vindicated even earlier than we expected.

It is definitely not the case that the end of the pandemic is in sight, as claimed by various colleagues as well as some government leaders in May and June of this year. The reduced efficacy of the first-generation vaccines against the recently arrived and now prevalent Delta variant has introduced an element of considerable uncertainty that is also impacting on forecasts for the global economy.

As indicated in the previous Keynote, our current focus in the research we perform on behalf of our clients is on deciding whether their needs are best met by receiving a booster jab or by waiting for a next-generation vaccine to become available and, in either case, what the optimum timing might be.

We have already established reference values in our retesting procedures for antibody development and T-cell immunity, and we are confident that the WHO will adopt similar or even identical values by the end of the year. These are now the clear reference values for all our clients in deciding whether there is a need for action to ensure immunity against the SARS-CoV-2 virus and its mutants. This gives rise to a number of questions that we will clarify individually for each of our clients. The two key questions concern the timing and the choice of vaccine, specifically whether this should be a booster shot of the same vaccine. A third dose of the BioNTech vaccine can have the effect of increasing antibody counts by as much as fivefold. This is an attractive option for those clients who have antibody levels of less than 1,000 BAU/ml and thus far below our reference value.

The alternative is to wait for the next generation of vaccines to become available. As also reported in the previous Keynote, BioNTech has developed a proprietary vaccine to specifically target the Delta variant spike protein. This vaccine has already gone into production and is awaiting emergency approval from the FDA and EMA. Here, too, a fundamental decision must be made – booster or next-generation vaccine? What are the advantages and disadvantages?

The disadvantage of a next-generation vaccination could be that the next virus variant – and we have to assume that this already exists in the form of the Lambda or similar – could produce a change in the spike protein, thereby reducing the effectiveness of the newly developed vaccine, though not as much as that of its predecessors. This is the very race we wrote about several months ago and which is now well and truly underway. Unfortunately, the vaccine manufacturers are still in reaction mode at the moment, having to firefight the variants as and when they crop up. This consumes huge amounts of time and effort.

As to whether we are already on the home straight or only the opening lap of the race against new variants and whether the pace of mutation will pick up even further, Dr Robert Hess shares the general opinion that the odds are currently 50-50. In other words, there is a very real risk that the changes on the spike protein will become even more prominent. This issue carries over into the debate on super mutants.

On the assumption that the rate of mutation will continue to accelerate, this is a race that is going to be difficult to win. We still have the potential offered by artificial intelligence to make predictions about future mutations and thus stay one step ahead of the virus. But the probability of a super mutant has also increased significantly. The definition of a super mutant is that the virus has undergone a genetic change of such magnitude that the current vaccines become less than 20% effective.

The main argument against a third booster jab with the current generation of vaccines is that they are clearly less effective against Delta than against the Alpha variant, even if there are efficacy studies that seem to indicate the opposite. However, the number of people who are being hospitalized despite having been double-vaccinated is rising sharply in virtually all countries. In this matter, we have to disagree with our colleague Anthony Fauci in the USA, who attributes the problem of rising new infections to large numbers of non-vaccinated people becoming infected. This is certainly a major factor, but at the same time, the significantly reduced effectiveness of the vaccines currently in use is also a reason why the infection and hospitalization curves on the graph are heading upwards. In addition, there has been an increase in mortality in countries that have had the Delta variant for some time. The studies from Canada on the link between mortality and Delta as well as the latest data from the UK confirm that the new variant causes the death rate to rise. The scenarios differ slightly, in that the rise in number of cases in England is probably due to a relaxation of social distancing during the recent Euro 2021 Football Championship. But all in all, this is an indeterminate development that is very difficult to interpret.

The deliberations about the Delta variant, which have been going on in Europe for some time, have now also reached the USA. Delta was ignored there for too long, and in the meantime, there are districts in California where masks are once again being made compulsory in enclosed public spaces, even for vaccinated persons. The complexity of the situation is also global in the sense that political decision-makers are reluctant to issue any clear guidance on whether booster jabs or next-generation vaccines are the way ahead. For pandemic management and to achieve herd immunity, it is essential to have clarity on vaccination of children under 12 and teenagers. Because of the exaggerated immune response to vaccination, especially in younger age groups, the appropriate dosage should be based on the same categories that apply with any medicine, namely “Babies”, “Children”, “Adolescents” and “Adults”. These should be introduced as soon as possible as a crucial success factor in pandemic response. This is a move Dr Robert Hess was already calling for a year ago.

The politicians and licensing authorities are showing some reticence in regard to next-generation vaccines, for example the one from BioNTech which is already being developed and produced in Mainz (Germany), because of a fear that the prospect of their arrival in the near future might further reduce take-up of the current generation of vaccines. In almost all countries of the western world, vaccine hesitancy is already high, and the availability of an upgraded Delta vaccine would reduce vaccination acceptance even further. It is therefore a topic of discussion that is not wanted either politically or by the WHO, which is a rather unfortunate state of affairs.

The booster jab is also a politically sensitive topic because the majority of the world’s population does not yet have access to any vaccine at all. Meanwhile, first-world countries such as Israel have already embarked on their third round of vaccination. This imbalance is an added complication to the whole situation, with disturbing consequences such as were witnessed last weekend when vaccine poverty provoked anti-government demonstrations in the emerging countries of Tunisia and Brazil as well as in several Third World countries.

At the same time, the precise opposite phenomenon is manifesting itself in western countries where supplies of vaccines are more than adequate. In France and Italy, for example, there were also mass demonstrations at the weekend, albeit in opposition to mass vaccination. Against this background, it is wholly understandable that the WHO currently opposes booster jabs on principle.

All in all, the issue of booster vaccination has been taken up too late by the political decision-makers. We have been pursuing our retest strategy to continuously monitor the SARS-CoV-2 immunity of our clients since June, which has flagged up a disappointing decrease in antibodies and in T-cell immunity. This came as a surprise even for us, and so we were obliged to consider the issue of booster vaccination sooner than expected. We have therefore decided to make recommendations to our clients regarding booster jab or next-generation vaccine on an individual basis. We aim to be in a position where we can issue appropriate recommendations to our clients by mid-August.

Around the world, governments of all political complexions are steadily moving away from the imposition of mandatory social measures towards the individual taking responsibility for protecting his or her own health and safety and that of others. We intend to provide our clients with an even more focused basis for decision-making. The UK has adopted something of a pioneering role here. We have been very pleasantly surprised that the majority of the population there is behaving prudently and only using their restored freedoms in moderation. We think this is the right approach. Each individual must be allowed to map his or her own route through the pandemic.

It is not surprising that there are still people who do not want to be vaccinated. The main reason for reluctance is the side-effects of vaccination that have been observed so far. Of course, this is only a cautious analysis, because we have to assume that there will be a considerable increase in vaccine-induced autoimmune diseases in the coming years. The relevant data will begin to emerge only gradually. On the other hand, we already know for certain that Long Covid sequelae are more severe and more enduring than the side-effects of the vaccines. In this context, there are more and more warning signs, especially from the FDA and EMA, of capillary leak syndromes associated with the Johnson & Johnson vaccine. This can lead to acute episodes of oedema, mainly in the body extremities and when blood pressure is low. Another alert issued in connection with the Johnson & Johnson vaccine concerns Guillain-Barré syndrome, a rare inflammatory neural disease that may occur around the six-week mark after vaccination. There are also the myocarditis syndromes associated with mRNA vaccinations. Pericarditis, an inflammation of the heart muscle or the pericardium, is more often triggered after the second dose of the vaccine. The first instances of autoimmune disease have now appeared with the Moderna vaccine, specifically immune thrombocytopenia. These cases are being closely studied by both the FDA and the EMA. We see a clear link here with the vaccine. Another side-effect of mRNA vaccination is the occurrence of dermatological problems, namely delayed reactions in the form of skin eczema and hives that are usually associated with urticaria. These are triggered by so-called lipid nanoparticles that serve as a sort of protective packaging for the mRNA. These nanoparticles have the ability to activate the immune defense cells directly, so that large amounts of histamines (i.e. inflammatory messengers) are released. Where urticaria-like reactions occur, this is generally after the second shot of vaccine, and they can lead to severe complications such as asthma.

The AstraZeneca vaccine also contains a substance known as polysorbate 80, which is used as an excipient in some cosmetic medicines and also has considerable allergic potential. For this reason, we recommend heterologous vaccination (i.e. cross-vaccination) as standard, with a first dose of AstraZeneca followed by an mRNA vaccine as the second. Here, too, the vaccine side-effects can be considerable, and much stronger than with a homogeneous vaccination regimen. That is why we only recommend cross-vaccination in older people where immunosenescence (i.e. the gradual deterioration of the immune system brought on by aging) has set in.

The harm caused by Long Covid is much more difficult to assess, and we will discuss it in more detail in the next Keynote. From the data that is now beginning to accumulate, it is apparent that 80% of those who had symptomatic infections continue to feel worse after three months than they did before the onset of the disease. This is an alarmingly high percentage. A variety of check-ups and monitoring activities show that around 20% have sustained clearly detectable organ damage. The age group most affected by organ damage is between 40 – 50 years old, individuals who were previously relatively healthy and had no pre-existing chronic illnesses. Organ damage can even be found among the youngest cohort of 20-year-olds. There is an above-average number of athletes, which is probably down to the fact that the body feels completely different and that the perception of performance loss is therefore naturally felt more keenly. There are also neurological consequences ranging from disorders such as loss of taste, nerve pain and deafness to aphasia, significantly reduced cognitive and cardiological performance, shortness of breath, etc.

Understandably, the main focus of the check-up recommendations we make to our clients is on heart disease. This is because the endothelium in individuals who have survived Covid-19 has undergone massive changes and has essentially aged by many years. This manifests itself in cardiac insufficiency, cardiac arrhythmias and changes in the pulmonary interstitium that inhibit gas exchange and lead to respiratory distress. We will give an update on the consequences of Long Covid in the next Keynote.

As inoculation is a highly complex area, other scientific avenues are being explored involving different techniques. We have looked at three of them in some detail. Two come from a single country, namely Israel. We suspect that, should there ever be a solution that avoids inoculation, for example by means of a virus static, then the Israeli manufacturers will be at the forefront.

First, we looked at the oral Covid-19 vaccines produced by Oravax Medical, a company that specializes in this field. Clinical trials are already underway in Israel. We will monitor this development in detail and report back at a later stage.

The second solution comes from SaNOtize, another Israeli company. It is a so-called “anti-corona nasal spray” containing antibodies obtained from bovine colostrum which has already successfully negotiated clinical phase 2. Here, too, there is hope for success.

The third solution we will be pursuing from a poll of almost 20 companies drawn up by our research team comes from Australia, where CRISPR (clustered regularly interspaced short palindromic repeats) “gene scissors” have been deployed to inactivate the coronavirus. Here, too, the success rate does not look at all bad – it proved relatively easy to stop the SARS-CoV-2 from replicating in an infected cell. The results of the project have been published in Nature Communications magazine. It is an exceptionally interesting project for us because it concerns our own field of expertise, namely genetic engineering. Once the virus is identified, the CRISPR enzyme is activated, which then proceeds to dissect the virus. We will, of course, keep you updated on this development.

Pandemic Journal

CureVac were our great hope

Dr Robert HEss

Dr Robert Hess – 06/23/2021

CureVac was the great hope of Dr Robert Hess. They reached for the stars – and came back down with a bump.

Though the news was not entirely unexpected, we regret to report that the breakthrough vaccine promised by CureVac will now not be forthcoming. There are a number of reasons for this, but the main factor was the high demands that CureVac itself placed on the product. The aim was to develop a vaccine that was as natural as possible – ideally the most natural vaccine to date. In the end, it was the much-debated issue of vaccine-induced side-effects and long-term effects that thwarted their endeavor.

CureVac planned to optimize the “cell packaging” required for transport; this was to avoid having to make chemical changes to the product, as has been the case with vaccines from other manufacturers, in order to increase its tolerability. To fulfill this requirement, CureVac developed a highly natural mRNA-based vaccine. It was a risky strategy and one that ultimately failed, because the chemical-free packaging resulted in greater side-effects. This meant they had to limit the injection dose to 12 micrograms, which reduced the efficacy to just below 50%. By comparison, BioNTech sets its injection dose at 30 micrograms, while the Moderna is more than three times higher at 100.

CureVac also had the ambition to not only produce the most natural vaccine, but also to create one that would be effective against the mutations currently in circulation. With this objective in mind, the clinical phase 3 was delayed in order to include mutation events in the development stage of the product. In comparison to the three market leaders – Moderna, BioNTech and AstraZeneca – who tested only the original Wuhan wild type in their phase 3 trials, CureVac included all subsequent known mutations.

Unfortunately, this set the bar too high. CureVac even attempted to incorporate A.I. (artificial intelligence) into the prediction and detection of future mutations early on and to adapt their product to its findings. Essentially, the project failed because of the as yet insurmountable challenge of developing a natural vaccine that also covers current and even future mutations.

All in all, this is very disappointing news in the context of the pandemic, as governments and health bodies are counting on these next-generation vaccines to deal with future mutations by means of A.I. modeling. In this way, scientists would be able to get ahead of the game and anticipate viral mutations before they manifest themselves. As we have stated in previous Keynotes, we see technology as our only hope of bringing the pandemic under control.

There are other projects going down the same route as CureVac, for example the one at the University of Austin in Texas, but this announcement is still bad news for pandemic management.

Pandemic Journal

How long does the protection afforded by vaccination last?

Dr Robert HEss

Dr Robert Hess – 06/19/2021

How long does the protection afforded by vaccination last? This is a vital question that can only be answered when enough time has elapsed for results to come in.

There is one thing we can be certain of, however, namely that the protection afforded by vaccines does not live up to the claims made by their manufacturers. We strongly disagree with the assertion that “vaccine protection will remain at the same high level for approximately one year, so that we can get into an annual vaccination cycle like the one we have for influenza.” This is the reason why we set up our SARS-CoV-2 Antibody Profile Monitoring for Premium clients at the start of this year, measuring levels of SARS-CoV-2 antibodies as well as T-helper cells specific to SARS-CoV-2 and thereby covering both pillars of the immune response.

There are as yet no clinical studies to refer to, so we are in completely uncharted territory here. It is a matter of great concern to us that some of our clients who have been fully vaccinated for several months now appear to have built up little if any immune protection. In the circumstances, this monitoring of antibodies makes a lot of sense, and various scientific institutes have approached us to draw on our experience in this field.

Immune protection is, of course, also a subject of concern to the wider population, and many people, fearing that the immune protection they have gained from vaccination may already be weakening, are already asking for a third booster shot. The fact is that not a single scientific body has ventured an opinion on the matter. This means that Dr Robert Hess is entering completely new territory. We will not be making any general recommendations, as the individual situation of each client is different. The structure of each immune system is also highly individual with regard to natural immune response, vaccine-induced antibody levels and exposure to mutation events dependent on geographic location. We will therefore only make recommendations about booster jabs or next generation vaccines tailored to the individual client. We believe that it is simply impossible to devise a vaccination scheme in which the intervals specified are valid for everyone. This simply makes no sense. Consequently, a universal recommendation is completely out of the question.

Dr Robert Hess has also gained insight into the workings of the T-cells. First indications are that that they prevent severe infections, but not to the extent that has now been claimed in various scientific publications.

Furthermore, we also have to consider the special needs of so-called “low responders” or “non-responders” to the vaccines among our own clientele. We have to assume that such cases are more frequent than has been surmised so far. Low responders and non-responders are individuals who have acquired minimal or zero immune protection through vaccination. Among our clientele, we also have non-vaccinated Covid-19 survivors of whom around 25% have not built up any protection at all. This is a significant difference compared to measles, for example. The immunity of those who have recovered and those who have been vaccinated clearly decreases, and the curve falls away dramatically after about three months. The idea that there are people who cannot become infected has been absolutely refuted. Most people who have not been vaccinated will probably become infected at some point, but whether they end up as symptomatic or asymptomatic cases is another question. This is essentially what characterizes respiratory viruses in contrast to HIV, for example. There are people who are immune to the AIDS virus due to certain genetic polymorphisms which, by the way, we also measure as standard for our Premium clients. This is not the case with the novel coronavirus, unlike the Spanish flu, with which it is repeatedly compared: it has to be emphasized that the history of SARS-CoV-2 so far clearly points to each successive mutation event being more infectious and/or more dangerous.

The current prognosis of the Task Force of Dr Robert Hess still holds true: the pandemic is going to persist for a very long time, and the prospect that the virus will be with us forever is becoming more and more likely. This is because recovered and vaccinated individuals can still be carriers of SARS‑CoV‑2 and because the virus is mutation prone. There is also the potential for the animal kingdom to act as a reservoir for the disease – it is not yet known which animals can become infected with SARS‑CoV‑2 and spread the virus. From the case of the mink farms in Denmark, which we reported on in great detail a year ago, there are now very alarming statistics on how dangerous it is when animals also become infected. If we assume a similar regime as with influenza (bearing in mind that we have only moderate control over this less aggressive virus), then we will need to have an annual cycle of vaccination, because the previous year’s vaccines are never a perfect fit for the pathogens currently in circulation. This will definitely be the case with SARS-CoV-2 as well. Every year, the death rate from influenza in a medium-sized country such as Germany is around 10,000, sometimes even higher. In the more severe influenza years, for example on the American East Coast, the intensive care units are stretched to capacity. And if we add Covid-19 to the equation, hospital systems worldwide will have to be restructured.

As Dr. Robert Hess mentioned already, the level of protection depends on the sum total of antibodies, which obviously forms part of our monitoring. The antibodies are all directed against the spike protein, but not necessarily against the same regions. Many different types of antibodies are formed, which our monitoring classifies according to their effectiveness. In the case of a second infection, antibodies can even amplify the symptoms. However, the more antibodies there are in total, the greater the probability there will be some that also protect against mutations. The crucial question here is how high the antibody titer must be to protect against infection. In professional circles, we call this the “correlate of protection”, a figure that is usually defined by the WHO. Hepatitis provides a precedent: when the concentration of antibodies falls below a certain value, vaccination is called for; as long as it remains above that value, vaccination is not required. This is how the disease is managed. No such value exists for SARS-CoV-2, as no studies have been done on this so far. From our own SARS-CoV-2 antibody monitoring, we assume an average value of at least 3,000 BAU per mL, where BAU refers to binding antibody units with the relevant average efficacy classification.

Among the low responders and non-responders, there is a large group of people who take medications that suppress the immune system, or who have a donor organ and take drugs that prevent the immune system from rejecting it. This inevitably has the consequence of making pathogens difficult to fight off, but at the same time, the reaction to vaccine antigens is also weakened. This is a situation that affects patients who have to take anti-cancer drugs that affect the functioning of the immune system. Some of these medications can almost completely eliminate the B lymphocytes, which are important for the formation of antibodies. This is because the immune response occurs in several parallel pathways. The reaction to antigens produced to counter pathogens or derived from vaccination depends on how well the individual pathways work. One level is the antibody response, for which the above-mentioned B lymphocytes are indispensable. For example, rituximab, which is prescribed to alleviate certain types of cancer or arthritis, prevents the formation of B-lymphocytes and as such is a drug that needs to be taken into account here. Furthermore, there are steroids and antimetabolites that inhibit cell division and thus impair immune function in various ways. Added to which, there are the calcineurin inhibitors, such as cyclosporine and tacrolimus, which alter the T-cell response, namely that part of the immune response that may offer a certain long-term protective effect.

In non-responders with rheumatic diseases, their treatment usually involves a smaller number of immunosuppressive drugs. The dosage and effect are therefore less significant than with immunosuppression in organ transplant recipients or certain tumor patients. Nevertheless, a reduced effect is also to be expected here. The same applies to allergy sufferers who occasionally take antihistamines or use sprays and creams containing cortisone. There is definitely a reduced effect here, though by no means as drastic. We have already observed this with our Premium clients in the analysis of their antibodies.

In answer to the question of whether there is at least a T-cellular immunity in the case of a poor antibody response, we have evidence to support this, but not nearly as definitively as has been suggested in scientific publications over recent months. There have been indications that some immunity is gained, but at a far lower level than assumed. In our opinion, T-cells offer virtually no protection against actual infection, but they do make a severe course of disease less likely.

We already mentioned that we are working to build up T-cell specific immune response alongside antibodies. This development is eagerly awaited.

The question of whether mRNA or vector-based vaccines are preferable for the low-responder groups arises regardless of the reasons for their immune system deficiency. Ultimately, we have to assume that congenital immunodeficiency is a contributory factor with low-responders, irrespective of the risk groups just mentioned. This is confirmed for us on the one hand by the data derived from our own Premium clients, and on the other hand by the data that has come to us from the UK. To date, it has been shown that higher antibody titers can be expected after a first vaccination with an mRNA-based vaccine than after a first vaccination with a vector-based vaccine. As regards T-cell level, however, the situation is exactly the reverse: a higher value can be observed after a first vaccination with a vector-based vaccine. We should soon have the relevant data for the second vaccination. We see here that the combination of a first vaccination with a vector-based vaccine and second vaccination with mRNA can produce up to 10 times more antibody titers than if a vector-based vaccine is administered twice. As far as T cells are concerned, the combination of both principles also seems to be very effective. And that is why the best strategy for booster vaccinations has to be clarified with some degree of urgency. Our vaccinated clients have almost exclusively received an mRNA-based vaccine for both jabs.

Regarding the question of how a program of booster vaccinations might look, there are a couple of options available: on the one hand, a next-generation mRNA vaccine which also increases T-cell stimulation, and on the other hand (depending on the results in those affected), it may be possible to switch to a vector-based vaccine for the booster.

In conclusion, we can say that individualized vaccination schedules would be the optimal route to go down. I see it as my job to develop a long-term individual vaccination scheme.

Pandemic Journal

According to Doctor Robert Hess, the Delta variant is not the dreaded super mutant

Dr Robert HEss

Dr Robert Hess – 06/18/2021

According to Doctor Robert Hess, the Delta variant is not the dreaded super mutant, but it may be a game-changer in a negative sense.

In various parts of the UK, incidences are rising sharply again; the seven-day rate, which has long been around 20 new infections per 100,000, has recently risen to over 90. Mass testing has now been started in the north-west of England and the vaccination campaign has been stepped up.

Delta has twelve genetic changes in its spike protein compared to the original Wuhan strain discovered in December 2019. However, it has no changes at positions 501 or 484 of the receptor binding site, which I are closely monitoring. These mutations have so far been detected on the Beta (South Africa B.1.3.5.1) and Gamma (Brazil P.1) virus variants and defined as escape mutations. In the case of the Delta variant, however, the relevant change is the L452R substitution in the spike protein. Initial experiments in the laboratory suggest that it significantly boosts binding to the ACE 2 receptors, making it more infectious on the one hand and more dangerous on the other. This means that the risk of infecting a person from the same household is 60% higher with Delta than with the previously dominant Alpha variant; in other words, it is much more easily transmissible. This is apparent not only from the increase in the number of cases but also from contact tracing. The percentage of infected contacts is higher at 12.5% than for persons infected with B.1.1.7 at 8.1%. Data from the UK also indicate that individuals who contract B.1617.2 are at greater risk of ending up in hospital than those who contract B.1.1.7. These statistics make it clear that Delta is not only more infectious, but also more dangerous.

In a study just published in the Lancet, medical experts looked at how effective the antibodies produced by vaccinated individuals are against the Delta variant. The good news is that everyone who received two doses of their particular vaccine developed antibodies against the spike protein of SARS-CoV-2. The bad news, however, is that these antibodies are clearly less able to neutralize the Delta variant than the wild-type virus by a factor of more than 5.8.

For those who have received only one vaccine dose, the effect was even more worrying. 21% did not neutralize the wild type very effectively. For Alpha it was 50% and for Beta (i.e. South Africa) it was as much as 75%. The antibodies produced by a single dose were to all intents and purposes ineffective against the Delta variant in 80% of cases. These findings are clearly at variance with the report issued by Public Health England in which it was stated on a purely empirical basis and without any clinical evidence having been gathered that double vaccination could prevent 96% of hospitalizations. We are deeply skeptical of this claim.

Another study from England with a much better design shows that effectiveness against the Delta variants is clearly reduced, with a single dose of an mRNA or vector-based vaccine protecting against a symptomatic course of the disease in only 34% of cases. By comparison, a single jab protects in 51% of cases caused by the Alpha variant. Efficacy is thus clearly reduced by the new variant. After two doses of an mRNA vaccine, protection against Delta is 88%, slightly lower than the 93% efficacy rate for Alpha. The equivalent rate for two doses of the AstraZeneca vector vaccine is 60% protection against symptomatic disease with Delta and 66% with Alpha. The UK government has already responded by postponing the lifting of all restrictions, originally planned for 21st June, by four weeks. This change was of the utmost urgency, as Prime Minister Johnson announced it immediately after the G7 summit. What has been dubbed “Freedom Day” has now been postponed to 19th July.

The UK is once again at the focus of our attention because, in the western world at least, it is “Delta land” par excellence and, at the same time, it is a leader in the field of gene sequencing. It therefore makes sense for other countries to closely observe what is happening there. The current scenario is also absolutely fascinating for us as scientists. Infections have increased in the UK by 64% in the last few weeks. In the worst-affected areas, cases are even doubling every week. The link between infections and hospital admissions has weakened, but it has not been broken. The number of people in intensive care units is also growing again. According to Public Health England, 91% of new cases are now caused by the Delta variant. Our prediction has been validated, and the race between mutations and vaccination is vividly illustrated here once again. How quickly can the vaccination program be implemented? How well will the vaccines work? And how soon will the next mutation emerge? What is still unclear are the numbers of Delta patients admitted to hospital who had been vaccinated. At the moment, we have three different figures which range between five and twelve percent, so we cannot say that the vaccines are forming a solid wall of defense against these mutations so far. We endorse the four criteria laid down by the UK for mapping the way out of the crisis.

1) the progress made by the vaccination campaign

2) the efficacy of the vaccines

3) the burden on the health system and

4) the risk posed by new mutations.

We predict that the fourth criterion will be the most challenging worldwide.

Looking carefully at the mutations observed in the Delta variant, it is clear that this is definitely not the dreaded super mutant that would ultimately render the entire vaccination strategy futile. It is only a foretaste of what may lie ahead.

Even in other countries that already have a high vaccination rate, such as Chile, the infection rate continues to rise, although the Delta variant has not yet made an appearance there. In Chile, they are still struggling to control the P1 variant. Due to the non-homogeneous vaccination regime in the country, where mRNA- and vector-based vaccines are being administered alongside protein vaccines from China, it is not yet possible to make a definitive comparison of their effectiveness against P1. Ultimately, we have to conclude that, even with a high vaccination rate, a reduction in the number of infections is nowhere in sight, especially as winter is now beginning in Chile.

In Israel, another country that we are observing closely, the vaccination strategy has paid off so far. However, gene sequencing there shows that the Alpha variant still has a monopoly. It remains to be seen whether further mutations will be introduced into the country.

In Moscow, which has taken on the status of “Delta city”, the rate of infection is also soaring and the number of patients requiring artificial respiration in intensive care units has risen sharply.

We are working on the assumption that the antibodies triggered by the vaccines currently in use are therefore less effective. It is possible that, with an overall higher antibody volume, Class 1 of the neutralizing antibodies (i.e. those with the highest efficacy) will also increase and consequently be more effective against the Delta variant. I measure these levels every three months for our Premium clients.

We are now several months into the vaccination campaign

Dr Robert Hess 06/11/2021

Dr Robert Hess 06/11/2021

We are now several months into the vaccination campaign, and it is clear to us from our own SARS-CoV-2 antibody and immunization testing that the track record of the vaccines is very disappointing, with more side-effects than originally expected. We therefore intend to have a personalized vaccine combination in place for 2022.

It is the opinion of Doctor Robert Hess that ultimately it is clinical and biochemical data determining success rather than the phase 3 results quoted by the manufacturers, which are derived solely from empirical data. A gradual decline in immune status is to be expected, and this is also clearly evident from our retests. Here, the prognosis varies depending on the individual client and the vaccine regimen, but the basic tendency is towards a more rapid decline than that forecast by the vaccine manufacturers and the regulatory authorities. Autoimmune reactions are clearly apparent in the results of retests performed on our Premium clients.

Dr. Hess expected this, but not quite so soon. In the long term (i.e. over the next few years), he expects to see a veritable tsunami of autoimmune reactions, with a corresponding sharp increase in pathologies, ranging from allergies to multiple sclerosis. Furthermore it is to be expectedt that most of these side-effects will not be associated with the vaccines, because they will tend to manifest themselves as complex syndromes. And so we will be including more autoimmunological components in our retests to spot these conditions at an early stage. All vaccines, whether they are vector-based, mRNA-based or protein-based, elicit a very strong immune response. For example, a SARS-CoV-2 vaccine is up to 100 times more powerful than an influenza vaccine in terms of immune response. The likelihood of creating autoimmune side-effects is therefore correspondingly higher.

There are the direct side-effects of vaccination that are already known and which has been reported on several times before, especially those cases of thrombosis that can be directly attributed to vaccination and which generally occur with a vector-based vaccine. But in addition to these, we can already see autoimmune reactions associated with the mRNA-based vaccines. On the issue of myocarditis in people who have received the mRNA vaccine, we do indeed see a correlation manifesting itself. Here too, it is difficult to obtain specific figures because the resulting myocarditis does not trigger any immediate symptoms and initially goes unnoticed. This makes it very difficult to come up with any reliable statistics, and in any case, the diagnosis is highly complex.

Some time ago, Dr Robert Hess indicated that he would be extending the Standard Panel of Salvagene in this regard so as to avoid the need for the Premium clients to undergo a biopsy. Myocarditis is a condition that mainly affects men, especially in the younger age bracket. He believes that the very high levels of antibodies produced by the mRNA vaccines cause the body to overreact. The immune proteins can target the heart muscle cells in a similar way to viral infections and lead to inflammation. In our Covid-19 Immunization Program and retests, we will therefore have two clear focuses – firstly, to monitor overall immunization status, and secondly, to track and/or detect at an early stage the most significant long-term side-effects of vaccination.

For various reasons, we have to assume that the entire SARS-CoV-2 situation will persist in the long term. In particular, we share the opinion of our colleague Young Yang Gu regarding herd immunity. Doctor Hess will upload a separate podcast on this topic shortly. He can already state in advance that he does not consider world-wide herd immunity to be an achievable goal. The limited level of success, which is clearly demonstrated by the results of our retests, can be seen in the country with the most advanced vaccination program. In the UK, a successful vaccination campaign is underway, with 77% of the adult population already having received at least one jab, including 54% who have had two. On this basis, the government has now begun to cautiously open up the economy as the summer approaches, but it is in the face of a strong upward trend in infection rates, due of course to new mutant forms of the virus. This is just a foretaste of the complications that mutations will cause in the coming weeks and months of summer and beyond. In the race between mutations and vaccine developments, the virus still seems to have the edge.

While waiting for researchers at CureVac, the University of Texas and other centers to develop AI-based vaccines to mitigate the pandemic, a further option is to combine vaccines. There are approximately 25 such projects currently underway, the most prominent of which is Com‑CoV in the UK, and they are all pursuing similar leads. The current thinking is that mix-and-match brings advantages as well as disadvantages. A straightforward combination, which is the current favorite, delivers certain benefits, but also entails huge risks, because each individual has a completely different starting point. Some need a much higher T-cell immunity, while others need much greater and more effective antibody production.

The circumstances of every individual are different. The big worry is the ease with which SARS-CoV-2 can produce escape mutants and also combine its well-disguised evasion of antibodies with increased transmissibility. One example is the delta mutant, B.1.617.2, which originated in India and is responsible for the exponential growth of infection in the UK. It significantly raises the number of already existing loopholes for infection in vaccinated people. Such viruses continue to evolve in vaccinated individuals and learn to overcome vaccine protection even better. He has already stressed in previous Keynotes that the vaccinated are the very group that should be tested the most and whose results should be submitted for gene sequencing. The big risk is that no country in the world currently has the capacity to carry this out. Nevertheless, the vaccines that have been developed so far have the potential to control this infection in the long term. Each vaccine leaves gaps yet also has its particular advantages.

The question is, how can these strengths be intelligently combined to enhance their effect and provide better protection? These are the theoretical considerations behind one of the projects that Dr. Robert Hess is pursuing with his partners. One thing is certain – there is no perfect combination regimen, because the disadvantages clearly outweigh the advantages. In the adaptive part of the immune system, there are two pathways to combating the pathogen. In the so-called B-cell response, the immune cells form antibodies according to structures found on the surface of the pathogens. Well-matched antibodies bind to these antigens (e.g. viral proteins), thus rendering them blind and unable to function. Viruses wrapped in a sticky antibody film can no longer penetrate the host cells. Precise though this system may be, it is also vulnerable. Because antibodies have to latch on to the surface features in order to become attached, any change to a building block at a site favored by a certain set of antibodies can render this group ineffective. Although dozens of antibody clones form against the virus spike protein replicated in the vaccine, some mutations change the shape of the protein to such an extent that the antibodies are no longer able to bind to it. For example, in a laboratory experiment with the new beta (South African) variant, seven out of ten antibody groups failed. And this is precisely what was discovered in the SARS-CoV-2 antibody monitoring conducted with the Premium clients of Salvagene.

In some cases, the class 3 antibodies, which are classified as low-potency, are dominant, while the high-potency ones accounted for only a few percent of the total. The second pathway of the immune response is the T-cells. These are the focus of our immunization strategy, because this is where each of us has the greatest scope for optimization. Dr. Hess would therefore urge all Premium clients to rigorously implement the list of immunization to-dos. We estimate that at least 60% of all immunization lies in our own hands, regardless of whether we are vaccinated or not. The T-cells take a little longer to spring into action, but then proceed even more combatively, hurling themselves into the melee with molecular poison darts and other weaponry – immune cell against invader. The T-cells are the defense that gives long-term protection against viruses, and that is why they are the main focus of our Immunization Program. We measure overall T-cell immunity levels at regular three-monthly intervals. The T-cells orientate themselves to the surface molecules of the pathogens and are not concerned with fine details but rather with coarser general characteristics.

For recognition purposes, T-cells need only a small part of the picture where mutations are less likely. Moreover, these snippets are often located in regions that change comparatively rarely. So far, these have been consistent with the wild-type coronavirus and its current mutants. Which is why those who have been vaccinated can still become infected with escape mutants, but do not become seriously ill. As already reported, there are advantages and disadvantages to the different vaccine platforms: vector vaccines stimulate the production of more T-cells, while mRNA-based vaccines produce more antibodies. For the sort of person who does little to boost their own T-cell immunity, combining the two types makes sense. Individuals who have received a vector-based vaccine characteristically have a lower antibody count and the antibodies that they do have can be bypassed relatively easily by the virus. On the other hand, the T-cell response is strong, though this comes with the risk of an exaggerated response in younger people, especially women. In contrast, the mRNA vaccines produce a more effective antibody response that is also stable against mutants. The response in the T-cell system, on the other hand, may be weaker. A direct comparison of the two main vaccines carried out as part of a study in the UK showed that only half as many people vaccinated with BioNTech had produced T-cells capable of neutralizing the virus spike protein compared with those who had received the AstraZeneca vaccine. The findings that vaccination with AstraZeneca produces a stronger T-cell response may be due to the fact that the properties of two viruses are combined, namely the proteins of SARS-CoV-2 with those of the adenovirus which serves as a sort of taxi.

Adenoviruses are even capable of penetrating into the cell nucleus, which should be a cause for great alarm. There are various studies on this, including one at Harvard, that suggest the provision of learning templates with different pathogens significantly improves immune response. The Harvard study covered 74,000 Covid patients who had already received either a combined measles, mumps and rubella vaccine or a combined diphtheria and whooping cough vaccine. These individuals exhibited superior immune levels to members of the control group. Research done in Spain showed that Covid patients who had pneumococcal vaccination were significantly more immune. As early as last autumn, we were recommending that pneumococcal vaccines should be administered, followed up by booster jabs. With all these studies looking at combined vaccines, not a single one has concerned itself with escape mutants. Consequently, great caution must be exercised. Results so far suggest that there are definitely vaccine combinations that are significantly better than the single-variety regimens. But it is already becoming apparent that there are combinations that are less effective or in which the immune response is actually slowed down. Regarding the combinations with protein-based vaccines, Dr. Robert Hess has taken an especially close look at the combination of mRNA-based vaccines with protein-based vaccines, specifically with Novavax. Here, the spike proteins of the virus are given an effect enhancer. In addition, the proteins are highly concentrated and biotechnically modified so that our immune system has the opportunity to study them at its leisure and build even more suitable antibodies. It is theoretically possible that this might have a significant potentiating effect on the antibody system. However, the combination no longer works if a purely mRNA-based vaccine has already been given first, because the antibody reaction is then already so strong as to render the protein vaccine ineffective. When the reverse order applies, i.e. the protein-based vaccine is administered first followed by a vector-based or mRNA vaccine, the studies showed a clearly potentiated antibody formation with an across-the-board T-cell response. This results in a significant mutant-resistant degree of immunization. It is already becoming apparent that there will be a multiplicity of vaccine combinations offering many different possibilities in the coming months. But at the same time, they will entail big problems and big risks.

Against this background, Doctor Robert Hess is working to develop a customized vaccine combination for his Premium clients, which logically still cannot be 100% perfect. This was also the reason why he delayed such a long time before making any recommendations to his Premium clients while the vaccination campaign was only just starting up. He wanted to keep the options open, and from his perspective, this approach has been vindicated.

However, in the case of a booster in a few months, the question will arise: What is the next step? We assume that the amount of inoculant, i.e. the quantity delivered via the vaccine itself, will also play a role due to the current immunization status. This will naturally entail in‑depth consultation.

With so many people wanting to be vaccinated at the same time, the immune response is already being pre‑formed in such a way that certain combinations will not work. The worst case imaginable would be that the version of the virus encountered first so strongly imprints the immune system that it is no longer able to switch over when it encounters another, more dangerous version of the pathogen. We are already investigating scenarios in which antibodies are produced that actually give the infection a helping hand. The phenomenon of “original antigenic sin” (also known as antigenic imprinting or the Hoskins effect) is known to us from other infections, for example dengue fever. There are different dengue viruses – so-called zero-types – which can trigger dengue fever. After a first infection with one zero-type, people can often become more severely ill with a second infection triggered by a different zero-type, because their immune system calls up the old immune response to the original virus, but struggles to adapt to the new one.

In the case of the novel coronavirus, it is still not clear whether the immune system is sluggish in relearning or whether it reacts with some degree of flexibility. This is an issue we addressed back in April 2020. It will definitely become clearer in the next few weeks as new mutants appear and the vaccination campaign forges ahead. There is an initial study by Moderna, the findings of which have been somewhat contradictory. Some vaccinated people have already received a third dose based on the blueprints of the original Wuhan virus and the so-called South African mutant, but the results are inconclusive as to what the scope for adaptation might actually look like.

In conclusion, Dr. Robert Hess believes that, although the vaccines provide a certain platform for a solution and it was not entirely unjustified that the lion’s share of investment went into them, they will not ultimately lead to a resolution of the problem. We should therefore consider going down the second more broadly based route of antivirals, and there are already many promising projects in this regard. In the next Keynote we will look at these in a bit more detail.

As for the long-term prospects, we believe that this approach, alongside vaccines with their concomitant risks, will produce a manageable solution with very few side-effects and a significantly greater acceptance among the general population.