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Pandemic Journal

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.

Pandemic Journal

The skepticism of Dr Robert Hess regarding the efficacy of all previous vaccines against the Delta variant has been confirmed

Dr Robert HEss

Dr Robert Hess – 07/20/2021

The skepticism of Dr Robert Hess regarding the efficacy of all previous vaccines against the Delta variant has been confirmed by the announcement from BioNTech/Pfizer that they are working on a vaccine that will specifically target this mutant.

The Delta variant of the novel coronavirus, which is causing concern across the whole of Europe, is now starting to show up in America. BioNTech and its manufacturing partner Pfizer announced last Friday that they are developing an updated version of the Pfizer/BioNTech Covid-19 vaccine that will target the complete spike protein of this latest variant. They also stated that the first batch of this vaccine consisting of approximately 20,000 doses has already been produced at the Mainz plant in Germany. The clinical trials are due to start in August this year.

It was seven and a half months before the original vaccine received official approval, but for the adapted version, the procedure could be accelerated. The urgency is even Dr Robert Hess because scientists have detected new mutations in the meantime that are significantly more complex. This confirms that we were right to express our reservations about the effectiveness of the current crop of vaccines against the Delta variant.

We have always taken with a pinch of salt the headline figures, which tend to be empirical, have so far not been backed up by any clinical study and are primarily intended to shape public opinion. The Pfizer vaccine is the best to have emerged to date, so with the decision by the clear world market leader to go down this route, we see our assessment as being vindicated. Based on information from unofficial sources, we have reason to believe that nearly all vaccine manufacturers are now engaged in developing new vaccines against the spike protein of the Delta variant. So the question now arises as to what happens next with booster vaccines. The Pfizer/BioNTech team are already planning far ahead, having notified FDA, the EMA and other regulatory authorities of their intention to submit an application for a third dose booster jab. We interpret this as confirmation of our assessment that the protection afforded is significantly reduced due to the relatively low antibody production of the vector-based vaccines, and the insufficient T-lymphocyte-based immunization provided by the mRNA vaccines. This is precisely what our Covid-19 antibody and T-cell monitoring has been confirming for some time. The protection conferred by vaccination persists for a much shorter duration than expected, and the purpose of the third jab is to boost immunity sooner than was originally envisaged.

A conservative estimate is that a third dose is needed six months after the first course of vaccination to maintain the highest possible protection. While the FDA has not yet made any response, the EMA is already signaling that it would be premature to issue any statement either way, because there is not yet enough data from the vaccination campaigns and ongoing studies to draw any conclusion. In this matter too, we disagree with the EMA, because there are clear indications that vaccine immunity is significantly lower and lasts for a shorter period than expected. For this reason, we cannot understand the hesitancy on the part of the EMA.

The crucial point is that full vaccination against the Delta variant has to be the priority. With regard to the first round of vaccination, there is an excellent paper from the Pasteur Institute in Paris, which was published in Nature magazine. Here, AstraZeneca and BioNTech/Pfizer vaccines were tested for efficacy against the Delta variant. Only 10% of recipients were protected after a single shot, but the figure rose to about 95% after the second dose. However, we consider these estimates to be wishful thinking. The findings suggest that the first vaccination offers virtually no protection against the Delta variant but that the success rate is significantly enhanced by the second dose. However, all of our Premium clients have already been double jabbed, so they have already jumped over this particular hurdle. There are many millions of people in Europe who have not yet followed up a first dose of AstraZeneca with a second. These people are virtually unprotected against the Delta variant.

The same paper from the Pasteur Institute addresses the question as to whether individuals who have recovered from a first bout of Covid-19 are resistant to the Delta variant, and the answer is an emphatic NO. Survivors must have at least one dose of vaccine to come close to adequate protection against the Delta variant. Unlike the EMA, which recommends that this booster vaccination should not be given until six months later, we believe that the AstraZeneca follow-up jab should be administered 8 to 12 weeks after recovery.

We have identified relevant cases among our Premium clients. Here, the situation is much more transparent, because our immunity testing allows us to give a clear diagnosis of the effects of an infection, based on T-cell immunity and antibody formation. From these results, we make a personalized and individual recommendation as to when a booster vaccination should be carried out and with which vaccine. Because the WHO still does not give a reference value for immunity for both pillars, we are using our own findings as reference values to decide if and when a booster should be administered, or whether it makes more sense to wait for a complete solution based on the next-generation vaccines. Because the picture could change again in the autumn as new variants come along and, depending on the level of immune protection provided by vaccination in each individual, it will be necessary either to start completely “from scratch” with the administration of a next-generation vaccine, or to reinforce existing protection with a booster jab.

 protection with a booster jab.As things stand, we have to assume that a booster is necessary when antibodies, measured as BAU/ml, fall below 2,000. And of these, at least 70% must be neutralizing antibodies, of which again at least 30% fall into the highly effective category. In T-cell immunity, which is ultimately at cellular level, the interferon-Gamma release in the index should not be higher than 5.0, and the interleukin-2 release should not be greater than 2.0. Based on our clients’ own monitoring results, these are the reference values that we currently see as the benchmark for maintaining perfect immune status. They must, of course, be combined with all the other values that signify immunological response. For SARS-CoV-2 in particular, these are our reference values.

The fact that the vaccination campaigns in general are not really getting anywhere near tackling the Delta variant with the existing vaccines is a phenomenon that we have observed for some time in Israel and also in the UK. But in Israel, the trend is particularly noticeable. The country has had by far the speediest vaccination campaign in the world, yet now the daily incidence rate has risen to 450 per 100,000 population. That is one of the highest figures that Israel has had to date, and most alarmingly, 7% of those who have been completely vaccinated fall seriously ill and have to be treated in intensive care units. This is a very high rate, considering that Israel administered mainly mRNA vaccines. In the meantime, face coverings have again been made compulsory in indoor spaces. So here, too, we see the progress made going into reverse. Ignoring the EMA’s hesitant attitude towards approval, the Israeli government has started to administer booster vaccines to certain groups.

For this reason, we are again dubious about the recent statement issued by Johnson & Johnson that its own vaccine is 85% effective against the new mutant and that the immunity it confers will last at least eight months. Frankly, we are astonished by J&J’s assertion that protection lasts eight months when the Delta variant has only been in circulation outside India for the past ten weeks.

The consequences of the Delta variant are enormous. Many countries are initially ignoring the spread of infection, the UK being a notable example. Ultimately, it all comes down to political expediency. And in this context, we think we are heading in a direction where each person, individually and for themselves, devises their own strategy for coping with the pandemic in the coming years, because governments will increasingly withdraw from medical approaches and economic-political factors will instead guide their decision making. One such decision may, of course, be to adopt a policy of so-called “herd immunity” which assumes a 90-95% vaccination rate. This is a prospect that is looking increasingly difficult to achieve. We have had our reservations about the feasibility of herd immunity from the outset and see it as an unattainable goal at this stage.

Some countries remain very cautious, for example Norway, which has postponed its proposed step-by-step reopening. Other governments, such as the French, have gone even further and cancelled arrangements. There are countries where the Delta variant is beginning to circulate which have a very high vaccination rate, such as Chile. High infection rates are already being registered here, with severe cases being treated in intensive care units. This is not exclusively due to the Delta variant, but also to the fact that in these countries inoculation was mainly carried out with Chinese vaccines, most of which are protein-based and achieve efficacy rates of less than 50%. We are convinced that the protein-based vaccines will prove to be even less effective against the more dangerous mutations that lie ahead. And it has to be remembered that the Chinese vaccine products have not passed the rigorous standards of the major regulatory authorities in the western world, not least because data from the critical third phases of testing were never published in reputable peer-reviewed medical journals. There have been no estimates of efficacy in vulnerable, elderly people because too few subjects from this group were included in large-scale trials. Therefore, at least for the time being, the Asian vaccines are playing a negligible part in the fight against the pandemic.

In a recent Keynote, we made our forecast for this autumn in the northern hemisphere. We cannot share the optimistic predictions of a less harsh fourth wave next winter, not least because the mutations already observed are showing another clear change of direction with the Delta variant.

This is where the excellent work being done by the Com-Cov research team in the UK comes into its own. A study on vaccination and cross-vaccination regimens has also begun in Germany. As we reported in a previous Keynote, AstraZeneca and BioNTech (or indeed Moderna) have different strengths that complement each other well. AstraZeneca is particularly good at triggering a T-cell response, whereas BioNTech mainly activates antibody formation. Both vaccines provide the immune system with minimally modified learning material, which is crucial, as was clearly demonstrated in the Com-Cov study. The second BioNTech vaccination is therefore ideal for retraining immune cells already boosted by a first dose of AstraZeneca.

In this scenario, the second vaccination with BioNTech helps the body to remove unsuitable antibodies and T-cells from the body, of which there is an abundance after the AstraZeneca vaccination, thereby enabling the immune system to respond even more efficiently to the pathogen. These additional, unsuitable antibodies are precisely those which, in our view, could constitute the so-called “infection-enhancing” antibodies. We have seen data from the Charité in Berlin that also point in this direction. Should the merits of “mix-and-match” vaccination be confirmed, it will of course be included as an option in the individual strategies we devise for our Premium clients.

Pandemic Journal

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.

Pandemic Journal

The SARS-CoV-2 T-Cell immunity analysis

Dr Robert HEss

Dr Robert Hess – 07/09/2021

The SARS-CoV-2 T-Cell immunity analysis is to be integrated into the Covid-19 Immunization Program for Dr Robert Hess 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, we go 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 the Covid-19 Immunization Program for Dr Robert Hess clients with immediate effect.

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.

On 30th March 2021, the WHO Commission of Inquiry issued a statement

Dr Robert Hess

Dr Robert Hess – 06/01/2021

On 30th March 2021, the WHO Commission of Inquiry issued a statement to the effect that a laboratory accident as the cause of the pandemic was “extremely unlikely”. The skepticism we expressed at the time about their findings is now being vindicated.

The reevaluation of the surrounding circumstances by U.S. media, leading European scientists and even White House officials is not based on any new evidence, and nothing new has come to light, so we are more than surprised by the traction that the theory is gaining. At the same time, we take quiet satisfaction that our assessment at the time is now considered plausible by professional colleagues and by serious political institutions. What is supposedly new is in fact a republication of an article in the Wall Street Journal from November 2019 concerning three employees at the Wuhan Institute of Virology (WIV) who became so seriously ill with cold and flu-like symptoms that they had to be treated in hospital.

Just a fortnight ago, Science magazine published an article and open letter signed by 18 prominent experts calling for the investigation to be reopened. There is no smoking gun pointing to a laboratory leak, just as there is no proof that the virus has a natural origin. Consequently, the authors of the article have plumped for a 50:50 probability, compared with our odds of 60:40 in favor of a laboratory accident. And that is the order of likelihood we are standing by.

The authors of the Science article were stung into action by the official conclusions of the WHO Commission of Enquiry on 30th March 2021 which rated a laboratory accident as “extremely unlikely”. We strongly disagreed with that at the time and said so in no uncertain terms. We also expressed the view that this investigation was a farce. Even the WHO chief Tedros Adhanom Ghebreyesus has now voiced his own criticism, and that is quite astonishing, because ultimately he was the one who authorized the March statement. At the end of the day, it has to be conceded that the commissioners did not have access to raw data while they were in China, including information on previous patient samples from before December 2019, although they were allowed to visit some institutes and the possibility of a laboratory accident was given serious consideration. Tedros now admits that this investigation was inadequate. The mission was severely handicapped by the decision on the part of the Chinese government to “disinvite” colleagues with whom we work very closely, in particular the eminent German scientist Christian Drosten.

The commission itself had considerable internal conflicts of interest in its makeup. The team included Peter Daszak, head of the EcoHealth Alliance, a non-governmental organization that aims to protect health and ecosystems. In any serious investigation of a possible laboratory accident, Daszak would rank among the main suspects, because for many years the American worked together with the Chinese virologist Shi Zheng-Li. Supported by American funding that Daszak helped to source, Shi Zheng-Li was researching the coronaviruses found in bats; he captured them in the nearby caves and brought them to the Wuhan Institute of Virology over a period of 15 years. The aim of the project was first to clarify the origin of the SARS 1 pandemic and then to find out as much as possible about other potentially dangerous coronaviruses. So, the question arises: could the honorable intention to prevent a pandemic have been the trigger for the one we are now experiencing?

The theory of a laboratory accident is given added credence by the fact that the pandemic started in Wuhan. There is a general consensus that SARS-CoV-2 will originally have developed in horseshoe bats, a species widespread in Southeast Asia. But where did the virus make the crossover to a human or an intermediate host? At first, suspicion fell on a wild animal market in Wuhan. A conspicuously large number of the early patients had spent time there. However, further investigations revealed that there were also many patients among the early cases that had no connection to the animal market. The origin of the pandemic must therefore lie elsewhere. Wuhan is an ultra-modern metropolis, and it therefore unlikely that its inhabitants naturally come into contact with bats. She Zheng-Li found the closest relative of the SARS-CoV-2 virus in a mine in the southern province of Yunnan – 1,500 kilometers from Wuhan. This is only 86% identical to the novel coronavirus, meaning that decades of separate evolution have elapsed between the two viruses. However, it is conceivable that “patient zero” became infected with SARS-CoV-2 there or at some other location in China before traveling to Wuhan and spreading the virus in the city. However, there is a catch: if a virus jumps from one species to another, it can hardly happen overnight by a single change in the genome. Although an initial mutation can make the transition possible, the virus will at first be poorly adapted to the new host. Many further adaptations are necessary before a virus becomes so contagious that it can trigger a pandemic. In the case of SARS 1, which embarked on a short career as a pandemic in 2002, it has been possible to trace the many transformative steps, some of which involved viverrids as intermediate hosts. Traces of any such adaptation are missing for the SARS-CoV-2 virus. The genetic sequences recorded in the first patients at the end of 2019 are remarkably uniform.

The novel coronavirus seems to have come into the world out of nowhere as an already perfectly formed pathogen. It is possible, of course, that its evolutionary traces have simply not been found so far, or that China is keeping them under wraps. What is striking about SARS-CoV-2 is that, although it is no longer circulating among bats, it can infect various members of the carnivore group, including minks, cats and dogs. It is therefore conceivable that the virus adapted on large fur farms, for example among the fluffy tanuki from which China sources fur trimmings to supply the global fashion industry.

At this point, we have to ask ourselves why, after more than 18 months of mink, cats and dogs becoming infected through human contact, not a single animal-to-human retransmission has been recorded worldwide so far. This is yet another factor indicating a laboratory accident as the more likely cause.

We can pursue the matter further and explore the possibility that the evolution of SARS-CoV-2 took place in a laboratory, presumably at the Wuhan Institute of Virology. Viruses have escaped from such high-security facilities before. In 1977, for example, an unusual flu virus went around the world. It caused mild symptoms, mainly affected people under 26 and its genetic sequence was identical to a variant that last circulated in the 1950s. One possible explanation for this could be that old samples were used in vaccine development, thereby allowing the virus to escape from the laboratory.

There are six recorded cases of the SARS 1 virus having leaked out of laboratories in three countries – Singapore, Taiwan and China. In 2003, for example, a 26-year-old student at the Institute of Virology in Beijing became infected, blithely got on a train and traveled to her hometown 1,000 kilometers away. The student’s mother then became infected and subsequently died. The Chinese authorities quarantined around 1,000 people and were able to contain the outbreak. If SARS-CoV-2 also escaped from a laboratory, however, the question arises as to how it could have originated there in the first place. Various researchers have been looking for clues. The American scientific journalist Likus Walter describes the chain of evidence in particular detail in a report. However, we do not consider most of the points mentioned to be scientifically plausible. He thinks that She Zheng-Li was conducting so-called “gain of function” experiments in Wuhan. In experiments of this kind, virologists combine the component parts of different viruses to create new functions. The viruses can also become more infectious as a result. The intention of such experiments can be inferred from the research proposals submitted. In one case, She Zheng-Li published a successful experiment.

Wuhan has conducted at least one such experiment under the direction of Ralf S. Barec, one of the world’s leading coronavirus researchers based at the University of North Carolina. Barec and She Zheng-Li published a paper in Nature magazine in 2015 about a project in which they used the SARS 1 virus as the basic structure and added the spike protein of another coronavirus. The new virus was then able to infect human cells. Significantly, Barec is among the authors in Science magazine calling for a more rigorous investigation of SARS-CoV-2.

Any conclusion we might reach is necessarily subject to revision, because until China makes the data more transparent, all possibilities remain open, but in our view with a laboratory as the marginally more likely explanation. A virus database at the WIV with 22,000 entries was taken offline in September 2019, and initial assurances by some virologists that SARS-CoV-2 could not be a laboratory construct are now considered premature and untenable. As it later turned out, globetrotter Peter Daszak was behind an announcement to this effect that was published in the Lancet in February 2020. At the same time, there are certain features in the gene sequence of SARS-CoV-2 that give rise to speculation about possible human manipulation.

So, the debate is set to continue. The initial reluctance of the scientific community to be drawn into what looked like a conspiracy theory and to appear too close to the Trump administration has proved to be a good thing, as such considerations no longer need to temper or cloud their judgment. However, the view of the Dr Robert Hess SARS-CoV-2 Task Force is that the chance of the mystery ever being solved is slim. At the start of 2020, China imposed a gagging order, whereby no one in the country was allowed to say or publish anything about the origin of the virus. Nevertheless, there is a body of evidence to be found outside of China.

We believe that, if more information comes to light, it should be possible to deduce the origin of the pandemic by scientific means. At the same time, it is known that U.S. intelligence agencies, as well as other Western intelligence agencies, are beginning to trawl through human and electronic sources, which may eventually provide the basis for science to get to the bottom of the whole affair.

It is possibly also a matter of significance that the pace of mutation has accelerated in the last fortnight, which is due to the vaccination programs. As we have already pointed out many times before, the virus is forced by the vaccines to activate, adapt and optimize itself by means of escape mutations. Unfortunately, there is very little awareness or acceptance among political leaders that it is precisely the vaccinated population who should be tested because of this issue and that more sequencing should be carried out as part of the tests.

The latest variant to have been detected in Vietnam is ultimately a combination of the British and Indian virus strains. It disperses very quickly through the air, so that the viral load in the throat increases much faster after infection and thus spreads very strongly in the environment. This makes it much more contagious than the previously known variants. The race between virus mutations and vaccine development goes on …