August 2021 -

Differing opinions about the Lambda variant

Dr Robert Hess – 07/29/2021

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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.

The SARS-CoV-2 T-Cell immunity analysis

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 analysis is to be introduced as standard in the Covid-19 Immunization Program for Dr Robert Hess clients with immediate effect.

CureVac were our great hope

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.

How long does the protection afforded by vaccination last?

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.

Monthly Archives: August 2021