Tag Archives: SARS-CoV-2

Dr Robert Hess: Recent studies have established a strong link

Dr Robert HEss

Dr Robert Hess – 09/03/2021

Dr Robert Hess: Recent studies have established a strong link between the presence of autoantibodies against interferon-I and a severe progression of disease after infection with SARS-CoV-2.

As we have explained in previous Keynotes, our body’s own interferon system plays an important role in the activation and modulation of the immune defenses. In this update, we will focus on what happens when there is a failure to activate the type I interferons (IFN-I) and on the risks that this poses. IFN-I is of immense importance in relation to the body’s own virus defense and thus highly relevant in the context of the SARS-CoV-2 pandemic.

Current thinking is that the functionality of interferon-I can be inactivated and/or neutralized by two mechanisms in particular: Firstly, a functional restriction can result from a genetic mutation, i.e. depending on the gene sequences in which the changes are located, it can distort the signaling pathway of interferon-I activation and thus weaken resistance to the virus. Studies conducted in 2020 were already able to establish a relationship between gene mutations of the interferon-I pathway and severe courses of the Covid-19 disease.

The second potential factor behind restricted IFN-I functionality are the so-called “autoantibodies”, which have been the focus of research for some time. Originally, it was assumed that autoantibodies were the result of a severe Covid-19 infection, but it is now looking more likely that they are in fact the cause. This realization is based on two independent studies that investigated the prevalence of autoantibodies against IFN-I in the healthy population and the presence of autoantibodies against IFN-I in severely ill Covid-19 patients. It was found that 0.18% of healthy 18- to 69-year-olds had autoantibodies against interferon-I and that this proportion increased with age: autoantibodies were present in approximately 1.1% of 70- to 79-year-olds and in 3.4% of those over 80. In the most recent study conducted in August of this year, scientists tested nearly 4,000 critically ill Covid-19 patients for autoantibodies to IFN-I. Overall, 13.6% of these patients had autoantibodies, ranging from 9.6% in those under 40 to 21% in those over 80. Autoantibodies were also present in 18% of those who died from the disease. Autoantibodies against IFN-I are therefore present to a certain percentage in the entire population, and their number increases with age. Taken in conjunction with other factors, it was therefore to be expected that there would be a connection between older age and a severe course of infection with SARS-CoV-2. Experts therefore recommend that patients suffering from Covid-19 be tested in hospital for potential autoantibodies against IFN-I and IFN-I mutations in order to better assess and predict the course of the infection. The role of autoantibodies – also in relation to other infectious diseases – has not yet been fully explored. We expect that further insightful findings on this topic will emerge from research in the future. As part of the C-19 immunization program, the interferon receptors and their activity level are regularly tested. This allows us to ensure the optimization of interferon receptors and thus improve immune response through therapy suggestions.

Dr Robert Hess: Any decision on whether to receive a booster jab

Dr Robert HEss

Dr Robert Hess – 08/17/2021

Dr Robert Hess: Any decision on whether to receive a booster jab (and which one to choose) or to wait for a next-generation vaccine should be based on the following criteria.

1 – Which is preferable – a booster jab or a next-generation vaccine? This depends on a number of factors, primarily which next-generation vaccine becomes available and when. It should be noted that the latest vaccine under development at BioNTech has been formulated exclusively to counter the threat of the Delta variant. We therefore need to carefully monitor how the virus continues to mutate, because the successor to Delta is already on the way. It may even turn out that, by the time the next-generation vaccine is ready for rollout, the current Delta variant is no longer relevant. At this point in time, BioNTech is the only manufacturer to have not only developed a next-generation vaccine but also to have produced an initial batch. However, it has not yet received official approval. Whether and when this is granted by the FDA will not be based on medical criteria, but on political considerations, namely how to persuade the public to receive the 700 million or so doses of the current vaccine if it became common knowledge that the BioNTech next-generation vaccine had already been approved.

2 – When is the moment to act? Before any action is taken, the individual status of each client has to be considered carefully. The three decisive criteria here are the most recent antibody count, the level of T-cell immunity and the general immune response. These reference values are then run through an algorithm by our AI system to determine the optimal timing of any further vaccination. The decisive factor is, of course, the general immune response and whether it is strong enough and operates with pinpoint accuracy in the event of an infection. This is precisely the purpose of our ongoing monitoring. And it is a good reason to keep taking the recommended supplements very regularly, even into the autumn.

3 – What would a sensible vaccination strategy look like? All three of the above criteria should be considered. For example, if T-cell immunity is weak and the first vaccination was with an mRNA-based vaccine, it would make sense to adopt a mix-and-match approach and switch to one of the vector-based vaccines, because these are better at improving T-cell immunity. The problem for our clients in the USA is that the only vector-based vaccine currently approved there is the Johnson & Johnson, and unfortunately, we are not convinced by the version currently available.

4– What else needs to be considered in deciding on further vaccination? A further criterion in taking the next step is the natural limit on the number of doses the human body can cope with in a given period. The underlying problem is that every vaccine, especially those developed to combat SARS-CoV-2, overstimulates the immune response, thereby triggering autoimmune reactions. We are of the opinion that no-one should receive more than 2-3 doses per year of the vaccines so far developed. Assuming that the pandemic will continue for a very long time, it is important to consider exactly when to vaccinate and which vaccine to choose in order to derive the greatest possible benefit. This way, the risk can be avoided of vaccinating too many times in a limited period of time, thereby putting a strain on autoimmune capacity and prompting autoimmune diseases in the future. After a finite number of vaccinations in a set period of time, of course, the autoimmune capacity has increased to such an extent that, at some point, the benefit has to be weighed against the cost. In other words, the harm done is greater than the risk of damage from Long Covid. That is why we have to be cautious about the number of vaccinations we subject ourselves to within a certain period of time.

5 – What are the potential advantages of a booster jab? If your next vaccination is to be a booster jab rather than a next-generation vaccine, then it must be taken into account that the current vaccines from Moderna and BioNTech are both approximately 30‑35% effective in preventing infection by the Delta variant, i.e. a relatively low rate of efficacy. On the other hand, our internal research and our contacts with BioNTech suggest that a third dose of their vaccine boosts antibody levels by a factor of four. In these circumstances, even a 30% success rate is a strong argument in favor.

Over the next few weeks, we will be checking these criteria as they apply to each of our Premium clients, using all available data. At the same time, we will set our A.I. system to calculate the optimum choice and timing on an individual basis. We will then contact you directly. If you have any questions in the meantime, please contact your consultant.

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.

Differing opinions about the Lambda variant

Dr Robert HEss

Dr Robert Hess – 07/29/2021

Differing opinions about the Lambda variant: Super mutant, successor to Delta or damp squib?

For the first time since the SARS-CoV-2 Task Force was established 18 months ago, a difference of opinion has arisen, specifically with regard to the Lambda variant. What everyone agrees on is that the Lambda or C.37 variant is clearly more contagious than the original Wuhan strain. In addition, it is much more resistant to antibodies, and the existing vaccines therefore have a reduced efficacy against it. The reason for this is three mutations in the spike protein, which render it less susceptible to neutralization by antibodies. Added to which there are two mutations that make the variant itself more infectious.

The WHO still has Lambda marked out as a “variant of interest”, as does the CDC, but there are other authorities, such as in Japan, that have classified it as a “variant of concern”. Some scientists argue that the Lambda variant could also have the potential to become a super mutant. At the moment, it is particularly widespread in Latin America. In vitro laboratory experiments show that this variant is clearly more contagious than the wild-type (Wuhan) variant, but at the same time less contagious than the Delta variant. The logical conclusion from the in vitro laboratory tests is that it cannot out-compete the Delta. The long-term prospects for the Lambda variant are thus unclear, and we will report on further developments on an ongoing basis.

The reduced efficacy of vaccines is a hugely important topic of discussion at the moment. More and more data is being published all the time, and in the EU alone, over 150,000 fully vaccinated people have nonetheless contracted Covid-19. The figures emerging from Israel on so-called “breakthrough infections” where the virus manages to breach vaccine defense show that not only low responders and non-responders are affected, but also fully vaccinated, healthy individuals. The reduced effectiveness of the vaccines has the consequence that, even in countries with high vaccination rates, intensive care units are slowly beginning to fill up again. Because increased numbers of younger people and even children are being taken to ICUs, especially in the USA, the question arises as to whether the Delta variant is especially dangerous for children. There is a lot of evidence pointing in this direction. The trigger is possibly the viral load, which is considerably higher with Delta than with the wild type or the Alpha variant and therefore increases the risk of hospitalization. More data is required if we are to reach any meaningful conclusion, however, and the SARS-CoV-2 Task Force will be focusing this in the next few days and weeks.

For our Premium clients who belong to either the non-responder or low-responder category due to a pre-existing health condition, we have developed further criteria. We monitor the development of antibody formation after the second vaccination and set other benchmarks specifically for low- or non-responders, because approximately 20% of our Premium clients come under this heading. Even fully vaccinated individuals who become infected and do not fall into the low-responder or non-responder categories can, of course, also have symptoms, although these may be much less severe, more resembling a flu-like infection, with headaches and a runny nose, sometimes even a cough. It must nevertheless be borne in mind that even fully vaccinated persons who become infected can go on to develop and suffer from Long Covid. A high temperature is reported relatively infrequently. This is because the adaptive (i.e. acquired) immune system, is able to keep the infection under control after vaccination has taught it the specific structures of the virus. A high temperature tends to occur when the innate immune system is called into action to fight an unknown pathogen with a much more non-specific reaction.

This is precisely where the problem arises with the forthcoming season of coughs and sneezes: if a relatively low rate of coronavirus coincides with a wave of common colds and rhinovirus, it is vital that people displaying symptoms stay at home and take a rapid test to clarify which of the viruses they have contracted. The problem is that they might otherwise pass on coronavirus to someone who has not yet been vaccinated and who might therefore be susceptible to a severe bout of Covid-19. Strict self-isolation should therefore be observed if even the slightest symptoms manifest themselves. A rapid test should then provide the necessary clarification. It is also important to remember that symptom-free vaccinated persons are also able to pass on the virus.

For the past one and a half years, we have been wearing face coverings, have kept a minimum distance from each other and no longer shake hands. With rhinoviruses, we know that post-infection immunity does not last long, which is why most people inevitably get repeat infections. Because we have not been exposed to these viruses for a long time, the likelihood increases of getting infected when exposed. Significantly more viruses are shed when an individual has contracted the Delta variant. Moreover, a much smaller volume of virus particles seems to be sufficient to infect another person. The upper respiratory tract is particularly affected. That is why sufferers often report nasal and throat symptoms as well as headaches. For the coming wave of influenza, it will be very important to quickly establish which virus is involved.

In the next two months, we will be making recommendations to our Premium clients on booster or next-generation vaccines against the coronavirus as well as other vaccinations that are appropriate for the autumn season and can help stave off a severe bout of flu, pneumococcus, whooping cough and shingles. With the exception of shingles, these are all diseases of the lungs. We work out the optimal protection against a flu epidemic for each of our Premium clients on an individual basis. And there is one further point to consider: if you have not yet been fully vaccinated with both doses of a coronavirus vaccine, please note that there should be a minimum two-week interval between a corona jab and a flu jab.

The preferred regimen against influenza is currently a high-dose quadruple vaccine. At least, that is the plan in Europe. In the USA, the decision has still to be made as to whether to go with triple vaccine as before or to upgrade to quadruple, which is looking increasingly likely. With the social distancing measures in place last season, the influenza wave was virtually absent, which means that much higher numbers are to be expected this autumn-winter season. It is important to reduce the risk of bacterial superinfection in case of SARS-CoV-2 infection.

Among the secondary diseases that are associated with Covid-19, special mention should be made of mucormycosis, also known as “Black Fungus”. It is spreads easily, many patients have died from it, and it is cropping up in countries all around the world. In New Delhi (India), for example, a separate hospital ward had to be set up because of the rampant fungal infection. We have to assume that secondary diseases associated with corona infection will increase along with the arrival of new mutations. Even the otherwise sensible wearing of masks unfortunately causes side-effects, especially in the case of children. One example is respiratory syncytial virus (RSV), a common cold virus that is harmless for most people but potentially deadly for infants, as instances throughout this summer have shown. The reason is that children have built up an “immune deficit” – the compulsory wearing of masks has meant that their immune protection has not been sufficiently trained and collateral damage has occurred. Against this background, we ask all Premium clients who have children under one year of age to contact their consultant to discuss a possible passive vaccination against RSV.

In one of our forthcoming Keynotes, we will be looking at the issue of vaccine-induced mortality in greater detail. On our Task Force, we have a pathologist who is researching this very issue. A year ago, we were already stressing the importance of conducting post-mortem examinations of individuals who have died from Covid-19 to gain a better understanding of the disease. On the other hand, we also think it is necessary to conduct post-mortem examinations of individuals who have died not long after being vaccinated, although this is a much more controversial matter. In previous Keynotes, we have reported in detail on cerebral venous sinus thrombosis (CVST) cases associated with vector-based vaccines. There remains a large gap in our knowledge here. Pathologists are generally not even aware that a deceased person may have recently been vaccinated. There are several university clinics and research institutions conducting studies into this whole issue. Previously, the sole focus of their attention had been on patients who died from Covid-19. More recently, they have also been looking at the rare but severe side-effects of vaccination. These include not only CVST and myocarditis but also autoimmune diseases.

The problem arises because vaccinated individuals, unlike Covid-19 patients, do not usually die while under clinical observation. The medical examiner then fails to make a connection with the vaccine and certifies the cause of death as natural or unknown, so that the authorities see no suspicion of foul play and release the body for burial or cremation. This procedure is standard in all OECD countries. We therefore have to assume that the number of people who have actually died due to vaccination is higher than officially reported. This conclusion is politically explosive, especially at a time when the vaccination campaign is running out of steam, when the Delta variant is spreading exponentially and politicians are considering the introduction of vaccine passports. The medical reasons for vaccination have to be weighed up on an individual basis, and as we see it, considerations of individual protection are being subordinated to the social policy objective of getting the whole population vaccinated as quickly as possible. Carrying out more autopsies of deceased patients who have been vaccinated would help to clarify matters, so that any causal link can be definitively ruled out or in.

This area of research could also significantly improve the further development of vaccines while boosting public confidence in vaccination in both the medium and long term. At this point, we have to remind our readers that, after more than a year now, no vaccine has yet been finally approved. BioNTech/Pfizer do, however expect their vaccine to receive approval from the FDA in the autumn.

In our previous Keynote, we had indicated that we expect the situation to become much more complex in the coming weeks, with the next step being the introduction of booster and next-generation vaccines. We are working hard to develop the best possible individual strategy for our Premium clients. The CDC has also begun to develop a concept for booster vaccinations for the coming winter.

In the political arena, too, a lot has happened, and the next move on the vaccine front is being mapped out as a priority by governments around the world. The EU has already ordered 1.8 billion doses from BioNTech for a possible third vaccination. Many countries are developing strategies for a third round of vaccination. While Sweden is looking to a possible start in 2022, Israel has already embarked on its third round of vaccination, and President Isaak Herzog has set an example by receiving his third jab.

As first world countries discuss booster vaccinations, the shortage of vaccines in the third world is inevitably going to lead to political tensions. The current dispute between the WHO and the German government is just a foretaste of what lies around the corner.

We discussed booster vaccinations and next-generation vaccines at great length in our last Keynote, setting out clear criteria for our Premium clients. As already indicated, we expect the WHO to adopt the same criteria. We are of the opinion that the mutation rate will most likely increase. Consequently, we would advise against booster or next-generation vaccines being administered too soon, because society cannot carry on vaccinating ad infinitum – every new vaccination is bound to trigger an autoimmune reaction. In most cases this is harmless, of course, but we have to assume that many autoimmune diseases will be further aggravated by the vaccines. So there is a natural limit to how often you should be inoculated. Consequently, one has to be very careful about deciding if and when to get a booster vaccination. The accelerated policy discussions on booster vaccination are being driven by the skyrocketing numbers, a prime example being Israel where significantly more people are having to be hospitalized despite its high vaccination uptake. Based on the first available figures from Israel, the side-effects of vaccination, at least with the mRNA vaccine, are similar to those of the second vaccination. The Israeli Ministry of Health has announced that the efficacy of the current vaccine has dropped from the original 39% estimated two weeks ago to a more realistic 29%. With figures in this range, it is unlikely that regular approval would be granted.

In the USA, too, some states are registering a new peak in infections, with more than 100,000 cases per day nationally. Florida alone has seen an increase of 50%. As a result, mask wearing has been reintroduced in some states, even for the fully vaccinated.

Israel has reverted to imposing restrictions and protective measures. In this regard, they are adopting a completely different approach than the UK where restrictions have been lifted entirely and the government is relying on the population to exercise common sense. In Britain, the number of deaths attributable to the coronavirus has risen to a daily high last seen in March. There is a strong push for certain groups to be vaccinated, for example pregnant women. We are in favor of this in principle, but only after due consideration on an individual basis. If you, as a Premium client, have any questions in this regard, please contact your consultant.

Meanwhile in Japan, the brakes are being slammed on because of the Delta virus. Hospital capacity is being stretched, not least because of the Olympic Games. Only the most serious cases are admitted to hospital, and the majority of those who fall ill have to stay at home and receive treatment from their family. In Texas, too, many hospitals have had to postpone elective surgical procedures. Our assessment that the Delta variant is extremely contagious is becoming more and more self-evident. The CDC also confirms that the Delta variant is at least as contagious as chickenpox. It is more rapidly transmissible than MERS (Middle East respiratory syndrome), SARS, Ebola or seasonal flu. Added to this is the fact that even vaccinated people with breakthrough infections of the Delta variant carry just as many viruses in their nose and throat as the unvaccinated and can thus spread the disease just as prolifically.

To date, there have been more than 200 million coronavirus infections and the official death rate stands at 4.25 million. By our own calculations, however, the number of deaths is closer to 12 million, a figure that the WHO has recently confirmed as being more realistic. We arrived at this total by subtracting the collateral damage caused by hospital occupancy from excess mortality over the relevant period. This is the same approach that is now being taken by the statisticians at the WHO. Calculated over 18 months, this number is far higher than that for influenza deaths in recent years.

The EU is also buying 200 million doses of Novavax from the USA, a vaccine that still has to be approved. We have our reservations about Novavax. However, due to the delay in approval, its Phase 3 testing has coincided with the current variants. This vaccine could potentially play a supplementary role. We are, of course, continuing to monitor developments here.

In the case of a booster vaccine, the correct timing depends on a combined score derived from the reference values for the three defining pillars, namely antibodies, T-cell immunity and general immune response. This score is calculated by means of an AI algorithm, taking into account the effectiveness of the current vaccines against the prevalent Delta variant. And of course, each calculation of the best and most sensible time for booster vaccination is made on an individual basis. We have further raised the reference values for the antibodies, in particular Class 1 antibodies (i.e. those with a low effect) of which much greater numbers are required to counter the significantly higher resistance of the Delta variant. We have also introduced a four-level classification of high responder, medium responder, low responder and non-responder for all Premium clients as a further parameter for the AI system. The calculation additionally takes into account any side-effects that manifested themselves after the first two vaccine doses were administered. On this basis, we are able to calculate the optimum interval before a third vaccination takes place. To date, there have been very few studies on this topic. We have at our disposal almost all the data that has been published so far, in particular from the USA. This clearly indicates that the interval between a second and a third vaccination should be around the six to eight months mark. Of course, the decision must also take into account whether it might not be more sensible to wait for a next-generation vaccination, for example the BioNTech version that has been formulated to target the Delta variant. Another option is to induce a heterogeneous immune response by means of a heterogeneous (mix-and-match) vaccination strategy.

The SARS-CoV-2 T-Cell immunity analysis is to be integrated into our Covid-19 Immunization Program

Dr Robert HEss

Dr Robert Hess – 07/09/2021

The SARS-CoV-2 T-Cell immunity analysis is to be integrated into our Covid-19 Immunization Program for clients with immediate effect.

So far, we have been testing only one of the two immunity pillars, namely antibody production. In addition to checking the full range of antibodies, Dr Robert Hess goes far beyond the generally applied classification to differentiate between the neutralizing antibodies and identify efficacy classes – low, medium and high – plus ADE antibodies which may even have the undesired effect of amplifying an infection. From now on, we will also be measuring the second Covid-19 immune pillar – namely T cell immunity – in great detail. For this purpose, we have upgraded our Covid-19 Immunization Program with the inclusion of the new SARS-CoV-2 T-Cell immunity analysis.

This supplementary CE-certified blood test facilitates the cellular immunological detection of a SARS-CoV-2 infection. Protection against Covid-19 afforded by vaccination is also shown in detail. It works by testing specific cellular immunity after a SARS-CoV-2 infection, as well as detecting immune reactivity against endemic coronaviruses, also referred to as background immunity.

The importance of the cellular immune response is as follows: an infection with or a vaccination against the SARS-CoV-2 virus should result in an activation of the adaptive immune system. Alongside the production by B lymphocytes of virus-specific antibodies, the stimulation and multiplication (clonal expansion) of virus-specific T lymphocytes is a central feature of this immune response. In the course of the acute immune response, the T lymphocytes first differentiate into effector T cells, which are actively involved in the elimination of virus-infected cells (CD8 killer T cells) and in controlling the function of other immune cells (CD4 T helper cells). The effector T cells are detectable as early as 10 to 14 days after infection or vaccination or after the onset of symptoms.

In the later stage of infection and after an individual has survived Covid 19 or alternatively been vaccinated against the disease, memory T cells should form and persist in the body, theoretically ensuring the maintenance of immune protection in the case of reinfection. If an individual is then exposed to the virus, the memory T cells can instantly trigger efficiently organized immune responses. In a coordinated response with neutralizing antibodies also present in the blood, the virus should then be rapidly repelled. Consequently, the detection of SARS-CoV-2-specific T cells is of particular importance with regard to the further spread of the virus and potential infection or reinfection.

Immunological diagnostics is a highly specialized field. The analysis of virus-specific T-cells in the context of routine laboratory diagnostics is no trivial matter due to the complex activation modality of these cells. Because T-cells are present in the blood only in low frequency or numbers, highly sensitive procedures are required for their detection.

The ELISPOT method, on which our SARS-CoV-2 T-Cell immunity test is based, provides a sensitive and specific analysis of T cells in the blood samples submitted by our clients. This cell culture test is based on the release of messenger substances from the immune system (cytokines) by single cells after stimulation of lymphocytes with virus fragments (peptides).

The fluorescence-based version of the ELISPOT method used for this test allows for the simultaneous detection of two different cytokines – interferon-y (IFN-y) and interleukin-2 (IL-2). While the production of IFN-y is characteristic of effector T cells, IL-2 is primarily secreted by activated memory T cells.

The ratio of T cells detected – active (IFN-y producing effector T cells) compared with residual (IL-2 producing memory T cells) – indicates the status of the T cell response and thus the current status of potential SARS-CoV-2 T cell immunity:

The confirmation by this cell function test of prior Covid-19 immunization succeeds significantly more often than with the serological determination of antibodies, as SARS-CoV-2-specific antibodies are not always detectable even with a PCR test following an infection. This is equally true in the case of an asymptomatic SARS-CoV-2 infection.

Two different peptide pools are used to stimulate the lymphocytes in this test. A positive T-cell indication after culture with the SARS-CoV-2 specific peptide mix is not only to be regarded as proof of a previous viral contact; with our current state of scientific knowledge, it can also be assumed that there is an existing cellular immunity, which gives the affected individual at least temporary immune protection. This is especially applicable in cases where IL-2-producing memory T cells are found in this test.

In addition, several studies have demonstrated the existence of cross-reactive memory T cells in Covid-19 patients and non-exported individuals which are derived from the immune response following infection with one of the endemic coronaviruses (HCoV-NL63, -229E, -OC43, -HKU1) related to the SARS-CoV-2 virus. Current thinking is that the presence of these T lymphocytes, which can be activated upon either infection with or vaccination against SARS-CoV-2, confers background immunity. This results in affected individuals becoming only mildly ill or not at all after infection or vaccination against SARS-CoV-2. To estimate the extent of such a putative cellular basic immunity, which is carried by the above-mentioned cross-reactive T cells, our test includes a stimulation of the lymphocytes with a PAN-corona peptide mix specific to the endemic coronaviruses.

Within the framework of our laboratory diagnostics for the Covid-19 Immunization Program, this new test is now available as an innovative cell function test that usefully supplements acute diagnostics by means of SARS-CoV-2 PCR (direct virus detection) as well as serological diagnostics with the detection of SARS-CoV-2-specific antibodies (IgG, IgM).

This analysis is to be introduced as standard in our Covid-19 Immunization Program for our Premium clients with immediate effect.

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.