Tag Archives: SARS-CoV-2

Dr Robert Hess: Antiviral drugs – One more strategic option in the fight against SARS-CoV-2.

Dr Robert HEss

Dr Robert Hess – 11/12/2021

Dr Robert Hess: Antiviral drugs – One more strategic option in the fight against SARS-CoV-2.

The development of effective drugs against COVID-19 has lagged behind that of vaccines. Recently, however, two major manufacturers have reported promising results from studies they have conducted. The UK has already granted approval to one of the new drugs. We assess the current state of play below.

On 4th November 2021, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) gave official approval to the world’s first tablet for treating persons infected with COVID-19. The antiviral drug molnupiravir, was developed by the pharmaceutical giant Merck Sharp & Dohme. This was followed one day later by an announcement from US-based competitor Pfizer that its paxlovid anti-corona pill had also shown high efficacy in interim clinical tests. Pfizer is now also trying to get its own offering approved quickly.


Just how effective are the new anti-corona drugs?

According to Pfizer, paxlovid, which is used in combination with an older antiviral drug called ritonavir, is very successful in preventing severe disease progression in high-risk patients. An interim analysis of test results showed that the drug reduced the risk of hospitalization and death by 89 percent in COVID-19 patients. This rate of success applied to cases where treatment was given within three days of the first COVID-19 symptoms manifesting themselves; similar encouraging results were observed for treatment within five days of the first symptoms appearing.

According to the preliminary results, paxlovid would appear to be more effective than Merck Sharp & Dohme’s molnupiravir. On the basis of a clinical study conducted by the manufacturer, this drug is claimed to reduce the risk of hospitalization and a fatal outcome by 50%, i.e. half of the rate for untreated patients. The drug has been approved in the UK for individuals who have at least one risk factor for succumbing to a severe course of the disease; these include a weakened or suppressed immune system, obesity, advanced age, diabetes and heart disease. The MHRA recommends that the medicament is administered within five days of the onset of symptoms.


How do the new antiviral drugs work?

Paxlovid belongs to the class of protease inhibitors. The active substance blocks an enzyme that SARS-CoV-2 needs to multiply. As a result, the virus cannot replicate itself in the cell and is therefore not able to infect any other cells. The viral load is thus very quickly reduced.


Molnupiravir from Merck has a different mechanism of action, which is designed to introduce errors into the gene code of the virus during replication. These mutations remove the virus’s ability to reproduce further. Because molnupiravir and paxlovid attack viral replication at different sites, it might even be possible to combine the two drugs. This is a conceivable scenario for exceptionally severe cases.


What are the advantages of antiviral drugs against COVID-19?

Molnupiravir and paxlovid are administered in pill form. This is a big advantage compared to previous therapy options – both remdesivir (the only drug approved in the EU for the treatment of COVID-19) and monoclonal antibodies have to be administered intravenously. Consequently, administration as a tablet is simpler, easier to manage and more manageable in an outpatient context.


What are the disadvantages of these two anti-corona pills?

Both paxlovid and molnupiravir must be taken in the first three to five days after the first COVID-19 symptoms appear. However, most infected people do not go to the doctor promptly, waiting until they feel really ill. By then, however, it may already be too late for treatment with antiviral tablets. According to Pfizer, paxlovid will not help save a patient who is already in intensive care.

Not much is known about possible side-effects of the tablets at the moment. The only information from Pfizer in this regard is that severe side-effects were less frequent in the treatment group than in the placebo group. This is a good sign for the time being. Before prescribing paxlovid, however, it is necessary to clarify the extent to which the protease inhibitors are compatible with other drugs, especially those that patients have to take because of pre-existing conditions.


When can approval be expected in the EU and the USA?

The European Medicines Agency (EMA) announced at the end of October that it would review the use of molnupiravir. After the drug was approved in the UK, the EMA stated that it now intended to speed up the review process. Molnupiravir is also pending approval in the USA.

In the case of paxlovid, Pfizer had already submitted an application for emergency approval to the US Food and Drug Administration (FDA) in October. The results of the clinical trials are now to be submitted to the FDA as speedily as possible using the fast-track procedure. Because of the impressive results, the trial involving around 1,200 volunteers has been brought to an early conclusion. Although approval is still pending, President Biden has announced that the USA has already placed an advance order for millions of units of the drug. The UK and Israel have also secured their first batches.


Will vaccinations become superfluous after the anti-Corona pills are approved?

The new COVID-19 drugs from Pfizer and Merck are so far no more than another weapon in our armory for combating the pandemic and, for the time being, should not be regarded as a substitute for vaccination. Declining the opportunity to get vaccinated at the moment is not a good option. However, we do not see the current vaccination regime as the ultimate solution.

The current crop of antiviral drugs are intended to treat those who actually contract the disease and do not yet offer any benefit in the area of prevention. The timing is also crucial: antiviral drugs cannot be used to treat patients in intensive care, because they have passed the point at which the medication might have worked. Furthermore, we cannot yet assess the extent to which the virus can be repressed by antiviral drugs or whether it could even form a resistance to their active substances. We know that individual treatments with inhibitors often lead to the development of resistance in viral diseases. For now, we have to wait and see how they complement the vaccines that are already available.


Whether the manufacturers’ claims will be substantiated in the long term remains to be seen. We see two main possibilities for the future, one of which is the familiar route of vaccination. However, provided we make further progress in the research area of antiviral medication, vaccination could recede somewhat into the background over time or become a bridging solution. Because, as we see it at the moment, vaccination is not the ultimate way out of the pandemic. The effect of vaccination does not last long enough to guarantee comprehensive protection, and it cannot be the goal to keep vaccinating the global population against coronavirus every 4-5 months. Vaccination compliance among the general public will decrease over time due to continued vaccine skepticism, vaccine breakthroughs and also undesirable side-effects. This situation could possibly be mitigated with effective antiviral drugs. Currently, antiviral pills are specific, but if it proves possible in the future to produce non-specific broad-spectrum antivirals, this could be a gamechanger.

We will continue to keep an eye on developments in this area and inform you about further research findings.

Dr Robert Hess: In case of Covid-19 infection – overview of current MAB treatment options.

Dr Robert HEss

Dr Robert Hess – 11/11/2021

Dr Robert Hess: In case of Covid-19 infection – overview of current MAB treatment options.

Currently, three anti-SARS-CoV-2 MAB products have received Emergency Use Authorization (EUA) from the FDA for the treatment of mild to moderate COVID-19 in non-hospitalized patients with laboratory-confirmed SARS-CoV-2 infection who are at high risk for progressing to severe disease and/or hospitalization. The issuance of an EUA does not constitute FDA approval.  

These products are:  

– Bamlanivimab plus etesevimab (US manufacturer Eli Lilly): These are neutralizing MABs that bind to different, but overlapping, epitopes in the spike protein RBD of SARS-CoV-2. The distribution of bamlanivimab plus etesevimab was paused in the United States because both the Gamma (P.1) and Beta (B.1.351) variants have reduced susceptibility to bamlanivimab and etesevimab. However, distribution of the agents has been reinstated in states with low rates of these and other variants that have reduced susceptibility to bamlanivimab and etesevimab.

– Casirivimab plus imdevimab: REGEN-COV. These are recombinant human MABs that bind to nonoverlapping epitopes of the spike protein RBD of SARS-CoV-2.

– Sotrovimab. This MAB was originally identified in 2003 from a SARS-CoV survivor. It targets an epitope in the RBD of the spike protein that is conserved between SARS-CoV and SARS-CoV-2.

Post- Exposure Prophylaxis:
The FDA has expanded the EUAs for bamlanivimab plus etesevimab and casirivimab plus imdevimab (REGEN-COV) to authorize their use as post-exposure prophylaxis (PEP) for certain individuals who are at high risk of acquiring SARS-CoV-2 infection and, if infected, are at high risk of progressing to serious illness.

Recommendations and Dosage:
The COVID-19 Treatment Guidelines Panel recommends using one of the anti-SARS-CoV-2 MAB products listed above (listed alphabetically and not in order of preference) to treat non-hospitalized patients with mild to moderate COVID-19 who are at high risk of clinical progression:

Bamlanivimab 700 mg plus etesevimab 1,400 mg administered as an intravenous (IV) infusion in regions where the combined frequency of potentially resistant SARS-CoV-2 variants is low

Casirivimab 600 mg plus imdevimab 600 mg administered as an IV infusion or as subcutaneous (SQ) injections

Sotrovimab 500 mg administered as an IV infusion.

When using anti-SARS-CoV-2 MABs, treatment should be started as soon as possible after the patient receives a positive result on a SARS-CoV-2 test and within 10 days of symptom onset.

The authorized anti-SARS-CoV-2 MABs should be administered by IV infusion or SQ injections and should only be administered in health care settings by qualified health care providers who have immediate access to emergency medical services and medications that treat infusion-related reactions. Patients should be monitored during the IV infusion or SQ injections and for at least 1 hour after the infusion or injections are completed.

This is an overview information sheet. If you find yourself in the position of having a Covid-19 infection or needing MAB therapy, please contact us immediately.
In addition to MAB therapy, there are other factors that need to be considered and therefore it is important that you contact us to help you manage such a situation as best you can.

Dr Robert Hess: What next for the SARS-CoV-2 pandemic?

Dr Robert HEss

Dr Robert Hess – 11/02/2021

What next for the SARS-CoV-2 pandemic?

The number of infections worldwide is on the increase, and with it, the number of vaccine breakthroughs. However, it is not only the rising rate of infection that is the root cause of this, but also the waning effect of the vaccines themselves. Nevertheless, individuals without any form of immunization are significantly less protected against COVID‑19 disease, and the mRNA booster jabs seem to be delivering on their promise of offering almost complete protection. There are multiple factors at play here that will continue to occupy our attention this winter. In the meantime, this is how we see the current situation. 

How prevalent are vaccine breakthroughs, and has their number increased? The number of vaccine breakthroughs worldwide is increasing. All manufacturers and vaccines are affected. A vaccine breakthrough occurs when a fully vaccinated person contracts a coronavirus infection with clinical symptoms.

According to the weekly report issued by the Robert Koch Institute (RKI), 95,487 fully vaccinated persons in Germany, have already been infected with the coronavirus since February. In the week of 27th September ‑ 24 October alone, almost 41,000 vaccine breakthroughs occurred among 18- to 59-year-olds. Measured across the entire period since the start of the vaccination campaign in Germany, the percentage of vaccine breakthroughs among symptomatic COVID‑19 cases in this age group has risen to 10.9. However, if we look only at the last four weeks, the ratio is significantly higher at 37.5 percent.
Increases can also be observed in the over‑60s age group, where the percentage of vaccine breakthroughs among symptomatic COVID‑19 cases is 16.1 for the period since the start of the vaccination campaign. And when we take the figures from only the last four weeks, this percentage increases to 58.9.
Other European health authorities are also reporting that, in some regions, half of the new infections are among the fully vaccinated, and the trend is unfortunately upwards. According to the UK government, four out of ten new hospital patients currently being admitted for coronavirus infection have been vaccinated.
In the USA, breakthrough infections were studied in six states – California, Colorado, Massachusetts, Oregon, Utah, Vermont and Virginia – as the authorities there collect the most detailed data on the disease. Whether their findings can be extrapolated to the entire USA is therefore unclear, but breakthrough infections in those six states accounted for 18 to 28 percent of registered cases during September. Among those who had been vaccinated, Johnson & Johnson recipients displayed slightly higher rates of vaccine breakthrough and of related deaths. Additionally, those vaccinated with Pfizer-BioNTech had slightly higher rates than recipients of Moderna, which can most likely be attributed to dosage differences.

Which age groups are affected?
Vaccination breakthroughs are occurring in all age groups. The proportion of breakthroughs is highest among individuals over 60 years of age. In both the EU and the USA, it appears that it is mainly older persons who are being hospitalized with the more acute infections, as well as individuals whose immune system is relatively weak or who have some sort of immunodeficiency. According to CDC data, 74 percent of vaccine breakthroughs occur in adults aged 65 and older.

Why are there so many vaccine breakthroughs?
The statistics show that vaccine breakthroughs tend to increase as more people are vaccinated against a particular pathogen. In the case of SARS-CoV-2, however, this is not the only reason, as multiple factors are involved here. Firstly, the virus now has renewed opportunities to spread, because most countries have relaxed their regulations on social distancing and face coverings, and because the northern hemisphere is entering the colder winter months. Secondly, the dominant form of the virus is still the Delta variant which is more contagious than the original “wild type” (i.e. Wuhan) or successor Alpha variant and also more successful in undermining vaccine efficacy.

In our opinion, the reason why vaccine breakthroughs have increased so rapidly, especially in recent weeks, is due to dwindling vaccine protection. Current studies even indicate that protection could be as low as 20 per cent only four months after the second dose of a COVID‑19 vaccine. Although a double dose is effective against the Delta variant, the protection it affords begins to diminish after only 30 days. A British study in August found that the effectiveness of the vaccine dropped to 90%, 85% and 78% after 30, 60 and 90 days, respectively. The data from such studies may vary, but the take-home message is that we too have observed the phenomenon of rapidly declining protection during the regular antibody level checks we perform on our clients. We therefore have to assume that the antibodies developed as a result of vaccination wane more quickly than was previously thought and generally published.

So, what are the causes of vaccine breakthrough?
Weakened immune system and age: An already weakened immune system will often be a decisive factor. This mostly affects cancer patients undergoing chemotherapy, patients with autoimmune diseases or the elderly. Especially in senior citizens, it is often the case that the immune system no longer responds adequately to immunization.

Mutations: Mutations also impair the effectiveness of the vaccine. The aggressive and significantly more contagious Delta variant reduces the efficacy of the vaccines. This is because this mutation is better adapted than its predecessors to evade the antibodies that are formed after vaccination. Although the current crop of vaccines are also effective against the Delta variant, more antibodies are needed to neutralize it.

Waning effect: As with almost all vaccines, the effect wears off after some time. This seems to be happening somewhat faster with the COVID‑19 vaccines than initially thought. Data from Israel gathered around mid-July 2021 was already indicating that the effectiveness of the BioNTech/Pfizer vaccine had begun to diminish. Israel was therefore one of the first countries to recognize the need for a follow-up booster jab. Their data showed that, after three months, antibody concentration was reduced by about half.

So, is vaccination pointless?
No, on the contrary. Vaccination protects against infection and, above all, staves off a severe course of the disease. Even if the protection against infection declines over time, protection against the potentially severe consequences remains. According to the CDC study, vaccinated people are eight times less likely to become infected and 25 times less likely to be hospitalized and/or die. A survey of intensive care units also confirms that most COVID‑19 patients admitted are unvaccinated. Data from the UK and Europe suggests that vaccination affords 90% protection against hospitalization. Among those aged 60 and older, protection against the risk of hospitalization is 86 percent. Corona vaccines protect against a fatal outcome by as much as 98 percent (87 percent in the over-60s). But in any case, the only sensible way to drive down the rising number of infections is to refresh vaccine protection with a booster jab.

How important are booster jabs?
Due to the rising numbers of vaccine breakthroughs, booster vaccination has taken on a new urgency. Some countries fear they will be entering a fourth wave around Christmas time, and governments are appealing to their citizens to get their booster without delay. But the vaccination program is faltering in many places, and the approach taken by individual countries also varies greatly. In Germany, the booster vaccine is so far only recommended for the over-70s and the immunocompromised. On Friday, however, the German health minister spoke out in favor of offering booster vaccination to all citizens. Sweden and the USA currently offer a booster jab to everyone over the age of 65 and the UK to everyone over 50 (as well as the immunocompromised, health workers, the occupationally exposed, etc.). Israel has already completed the majority of its booster vaccinations. The country was already battling a fourth coronavirus wave in the summer but now seems to have survived the immediate crisis. According to the Israeli health authorities, this is mainly due to the widely administered third vaccination against the virus.

Until now, all booster vaccinations have been given at least six months after the second dose of Pfizer/BioNTech or Moderna. The length of this interval is now up for debate, especially in view of rapidly declining antibody levels. Thanks to our capacity for monitoring the individual antibody levels of our clients, we have been able to ascertain that some would benefit from a booster jab as early as four months after the second dose. If the vaccine administered was J&J, a booster is already appropriate after only four weeks. This is an option that we also recommend, as we have found that the antibody gain from vaccination with J&J is insufficient.

With governments adopting so many different approaches and also national graphs peaking at different times, it will be interesting to see what stage the pandemic has reached in different countries two or three months further along the line.

What do initial data on the effectiveness of the Pfizer/BioNTech booster tell us?
The first full study has shown that a third dose of the Pfizer vaccine provides an “excellent” level of immunity. On 21st October, Pfizer/BioNTech shared results from their Phase 3 study involving more than 10,000 volunteers. These showed that the booster jab conferred 95.6 percent efficacy. In the half cohort who did not receive booster vaccination, 109 persons later became symptomatically infected. In the half who had received booster vaccination, this number was only five. It also showed that those who received a third dose of the Pfizer vaccine almost a year after their first two had higher protection against symptomatic infections than those who had received only two doses. An earlier study based on real-world population data from Israel found a similar increase in protection against serious illness.

Scientists believe that a decrease in the protection afforded by the first two doses is more than compensated for by the third. However, this refers only to a complete and exclusive series of Pfizer/BioNTech vaccination; there are no comparable data yet on the effectiveness of a third dose of Pfizer/BioNTech to top up a course of AstraZeneca or J&J. Two further studies on booster vaccines were also published in the October edition of New England Journal of Medicine. One found that antibody levels to the Delta variant increased almost tenfold after a booster shot of the Pfizer vaccine. We too have observed this antibody increase in our clients who had already received a booster vaccination.

The long-term prospects may at first seem somewhat daunting, but the data speak for themselves. SARS-CoV-2 will remain with us for the foreseeable future, and we will therefore have to learn how best to live with it. Although we may have hoped for even more ways to combat the coronavirus at this point, science never sleeps and we expect that there will be more to come in the future, including not only new vaccines but also drugs to treat a COVID‑19 infection. Apart from having a well-armed immune system, our defenses against a SARS-CoV-2 infection are “limited” to the best available vaccines. But this weapon seems to be effective enough when applied correctly and affords satisfactory protection for the time being. The realization that antibody levels decrease more rapidly than expected after a second dose of vaccine came as a surprise to many, but the phenomenon of diminishing protection over time is nothing new and can also be observed with many other vaccines.

Vaccines and subsequent responses by the immune system are under permanent review and subject to reinterpretation. While constant chopping and changing of rules and regulations may not always be entirely understandable and can at times be unsettling and demoralizing, it is the only realistic way to tackle the pandemic. We learn something new every day. The biggest advantage we see for our clients in this context is that we are not only privy to the latest research findings but can also incorporate them directly into our individual client concept. The specific data on each individual enables us to make precisely tailored recommendations regarding optimal protection against COVID‑19 and to use our own A.I. data sets in the process. Especially against the background of faster than expected decline in antibody levels and T-cell immunity, this puts us at an enormous advantage.

As we cannot yet predict how severe the coming winter will be, we would urge you to continue to maintain your immunity by following our general recommendations and taking your individually formulated supplements regularly. We will keep you informed and continue to advise you individually on booster vaccinations. If you have any questions, do not hesitate to contact our team of consultants.


Dr Robert Hess: The flu season is just around the corner

Dr Robert HEss

Dr Robert Hess – 10/28/2021

Dr Robert Hess: The flu season is just around the corner: What you need to know about the influenza season in general and high-dose vaccines in particular.

Social distancing, face coverings and strict hygiene controls not only reduced the spread of SARS-CoV-2 last year but also of influenza viruses. Flu activity is currently still at a low level, but nonetheless slightly higher than at this time in previous years. Researchers and authorities in the USA and Europe are predicting that a particularly virulent wave of influenza will hit the northern hemisphere in the winter months of 2021/22 and are therefore advising senior citizens to get a shot of the relatively new high-dose vaccines. What exactly are high-dose vaccines? And what can we expect from this year’s crop of flu vaccines?

Are we really in for a tough flu winter?

When a vaccinated or recovered individual is next exposed to the relevant pathogen, his or her immune system learns to attack in a speedier and more targeted manner. Last year, the flu season failed to materialize, and our immune systems missed out on the annual refresher course in combating the flu. Consequently, the influenza viruses may find it easier to spread this winter. Moreover, in the absence of the customary training, individuals are also less able to defend themselves against the flu because their own immune response is no longer as broad and effective. This is certainly the case for the unvaccinated.

Which flu vaccines will be deployed in the 2021/22 season?

Multiple influenza vaccines from different manufacturers are available in the USA and Europe. All vaccines contain the antigens specified by the WHO. Most licensed influenza vaccines for children and adults are of the inactivated kind, containing “killed” viruses or virus components, the only exception being Fluenz Tetra which is an inhaled live vaccine. The so-called tetravalent (alternatively quadrivalent) influenza vaccines protect against four different virus subtypes, namely H3N2, H1N1 (both of influenza A origin) and the two influenza B pathogens.

In Germany, a high-dose vaccine is now recommended for the first time this season for people aged 60 and above. In the United States, the high-dose flu vaccine has already been available since 2019. Containing four times the number of antigens, it could make a big difference in the coming winter season. Generally, any influenza vaccine takes up to 14 days to build up full protection.

What is the high-dose vaccine?

In Germany, the high-dose influenza vaccine goes by the name of Efluelda and is manufactured by Sanofi-Pasteur. Like the other influenza vaccines being made available this season, Efluelda is of the tetravalent variety and contains the vaccine antigens of the influenza strains as recommended by the World Health Organization. However, the dose of aCommittee on Vaccination (STIKO).ntigens is four times higher than in conventional influenza vaccines (i.e. 60 µg instead of 15 µg of hemagglutinin) for each of the four influenza strains. The EU Commission approved Efluelda for people aged 65 and over in May 2020, which was then extended to everyone aged 60 and over in February 2021. It is therefore fully compliant with the directions of the German Standing Committee on Vaccination (STIKO).

In the USA, Sanofi already markets the high-dose flu vaccine under the name Fluzone High-Dose Quadrivalent Influenza Vaccine. It was approved by the FDA (Food and Drug Administration) in July 2019. Sanofi Pasteur also previously had a high-dose flu vaccine in the USA, but it only protected against three strains of influenza. The trade name was Fluzone High Dose.

Why is a high-dose vaccine recommended for the elderly (60 or 65 years plus)?

Globally, nine out of ten people who are hospitalized or even die from influenza infection are older than 65 years. In the United States, between 70% and 85% of deaths and between 50% and 70% of hospital admissions related to seasonal flu occur in people aged 65 and above. This is partly because the human immune system declines with age. The weakening of the immune system can result in older people no longer responding well to the flu vaccine. The effectiveness of conventional influenza vaccines is as much as one-third lower in this group.

A study published in the New England Journal of Medicine showed that the administration of a high-dose vaccine in this group reduced the number of laboratory-confirmed influenza cases by 24% compared to a standard vaccine. In addition, the risk of hospitalization was reduced by almost 7%. A stronger immune response (i.e. higher antibody levels) was demonstrated, thereby vindicating the use of the vaccine to stimulate an aging immune system.

What about possible side-effects?

Due to its increased strength, a high-dose vaccine has a higher reactogenicity, so that local side-effects at the injection site (pain, redness, swelling) may occur more frequently. The symptoms usually disappear after a few days. As part of an Australian study, scientists conducted a survey on side-effects among almost 20,000 individuals who had received the high-dose vaccine. Around nine percent said they had some sort of reaction to the vaccine. The most common complaints were local pain, swelling with redness, and a high temperature.

Overall, the side-effect rate for the high-dose vaccine was about 30 percent greater than that for the conventional flu vaccine. Yet only 56 out of 20,000 high-dose vaccine recipients felt it was necessary to seek medical attention because of this. It is entirely to be expected that the immune system is stimulated more strongly by an increase in dose. This can be observed with almost all vaccinations. Researchers in European countries such as Germany can also draw on data from the USA, which has already been using the high-dose influenza vaccine for several years without any major problems.

To what extent are the high-dose vaccines compatible with other vaccines?

When injected in combination with other vaccines, the unpleasant side-effects are somewhat more noticeable. According to one study, this is especially true for the pneumococcal vaccine, which is often administered together with the influenza vaccine. The combination tripled the rate of those reporting temporary local pain or high temperature to 18%. When the influenza vaccine was combined with a herpes zoster virus vaccine against shingles, there were no increased side-effects. Regarding concurrent vaccination with a coronavirus vaccine (which is an approved method), we can expect reactions to be more common than when administered separately. However, unpublished data from the UK showed only slightly increased vaccine reactions. The immune response to both pathogens was also not reduced.

What level of protection do flu vaccines offer this year?

There are influenza A and influenza B viruses in circulation. The former are considered particularly dangerous. Influenza A viruses are divided into H3N2 and H1N1 viruses (H stands for the enzyme hemagglutinin and N for neuraminidase, the numerical element denoting different subgroups of the enzymes). Hemagglutinin and neuraminidase are the spikes that protrude from the surface of the virus and the most important recognition features for the defense cells. An immune system trained for H3N2 is therefore less able to defend itself against H1N1 pathogens.

Unfortunately, H3N2 and H1N1 pathogens regularly change details on their spikes, which is one of the reasons why a flu infection or vaccination does not necessarily provide immunity against the pathogens that come around the following season. For vaccine developers, the mutability of the flu virus means that they constantly have to adapt their vaccines.

Because production starts months in advance, the WHO closely monitors flu viruses circulating in more than 150 different geographical locations. Based on the data gathered, the organization identifies the pathogens for which the vaccines have to be formulated. The success of this forecast is variable and is the main reason why the effectiveness of vaccines fluctuates between 10 and 60 percent from season to season. An efficacy of 60% was last achieved in the 2010/11 season; in recent years, the efficacy has been between 30 and 45%.

The same applies to the influenza B viruses, except that they are less prone to change. They are divided into two types, the so-called Yamagata lineage and the Victoria lineage. However, the Yamagata lineage has disappeared from the scene since the pandemic and is possibly extinct.

The accuracy of the forecast for this winter can be gauged from Australian data. The current vaccine seems to protect very well against H1N1 and the B viruses, but for H3N2, the prognosis was less encouraging: according to the Australian Government Department of Health, all 20 H3N2 samples showed significant antigenic differences from the vaccine, indicating that protection against H3N2 could be in the low percentage range.

If you have any further questions on this topic or are unsure which flu vaccine you should choose (or indeed whether you should get vaccinated at all against influenza), please do not hesitate to get in touch with us. In the case of individual clients for whom we strongly recommend a high-dose vaccine, we will be contacting them privately.

Dr Robert Hess: Could the Novavax vaccine candidate be a viable

Dr Robert HEss

Dr Robert Hess – 10/22/2021

Dr Robert Hess: Could the Novavax vaccine candidate be a viable alternative for skeptics wary of mRNA technology? We take a look at new data on the protein-based inactivated vaccine.

Many people who are skeptical of mRNA technology have been waiting for a conventional vaccine against coronavirus to come along. “Classic” vaccines are traditionally based on proteins. However, the one formulated by Novavax has a major disadvantage, specifically its ability to provide long-term protection against virus variants. 

On 10th October, scientists presented the results of a Phase 3 trial involving almost 30,000 adults resident in the USA and Mexico. In the preprint, they report an efficacy of 90.4 percent against symptomatic infection with SARS-CoV-2. In September, the New England Journal of Medicine published results from a trial involving 15,000 volunteers in the UK which came to the same conclusion. Both studies were conducted before the Delta variant became the dominant form of the virus. It was observed that the direct side-effects of vaccination in the Phase 3 study were less noticeable with the Novavax candidate than with the mRNA vaccines. Novavax is also injected in two doses. Among the manufacturers of protein-based vaccines, the US pharmaceuticals giant is the furthest along in the approval process; its application has been running in the EU rolling review process since February of this year. The EU Commission has secured 200 million doses in anticipation of approval. Novavax plans to submit an application for approval of its vaccine in the USA this year. This was the state of play as of 15th October 2021. On closer inspection, however, the Novavax vaccine is somewhat less than conventional. The company itself makes reference to “innovative proprietary recombinant nanoparticle technology.” Although NVX-CoV2373 is a “killed” (i.e. inactivated) vaccine and is thus consistent with an established vaccination principle, it has also been given a new type of adjuvant to boost its effectiveness. This is based on a saponin extract obtained from the soap bark tree native to Chile. It is significant that the COVID-19 vaccines approved so far do not contain an active adjuvant.

The vaccine is produced in insect cell cultures, with up to 14 SARS-CoV-2 spike proteins being combined to form a nanoparticle which, for the immune system, resembles the virus itself. But the nanoparticle does not contain any genetic material – which is not only an advantage, but also a problem. This is because RNA or DNA content strengthens the immune response. This is part of the natural defense against infection, because regular pathogens also contain genetic material.

The adjuvant of the protein-based Novavax vaccine is apparently very effective, as indicated by the high efficacy in the studies. However, it cannot solve one problem of protein vaccines: they neither penetrate body cells nor do the multiply there. This means that the stimulation of the second arm of our immune system – the cellular immune defense – does not take place.

Vaccination can initiate a cellular immune defense response (T-killer cells, memory cells) as long as the vaccine enters body cells, something that Vector and mRNA vaccines are capable of. With protein-based vaccines, on the other hand, the cytotoxic T-cells are only marginally stimulated, with the main thrust coming in the form of antibody response. This makes it easier for the virus to become resistant to these vaccines because the immune response is not as broad.

This may also explain the results of a phase 3 trial in South Africa, where the efficacy of the Novavax vaccine NVX-CoV2373 against symptomatic SARS-CoV-2 infections was only around 50 per cent – possibly because of the local dominance of SARS-Cov-2 Beta which is the most efficient variant at evading neutralizing antibodies.

There are still some gaps in our knowledge about the various Covid-19 protein-based vaccines on the horizon. Furthermore, Novavax currently seems to be having problems with its manufacturing process. It is not yet clear if and when approval will be granted, but we will continue to monitor developments. We expect more news on this front in early 2022. Also on our radar is the vaccine from the French-Austrian company Valneva. They too have recently published the results of a Phase 3 trial of their inactivated vaccine VLA2001 and are likely to submit an application for marketing authorization soon.

By contrast, we already have extensive knowledge about mRNA vaccines. They are safe and have the best efficacy rate. In our opinion, there is no good reason to wait for future marketing authorizations before getting vaccinated.

Dr Robert Hess: Evidence that Delta does not make children more ill

Dr Robert HEss

Dr Robert Hess – 10/20/2021

Dr Robert Hess: Evidence that Delta does not make children more ill than other variants of the coronavirus.

The Delta variant of coronavirus does not appear to lead to a more severe course of disease in children than earlier forms of the virus, such as the Alpha or Beta variants. This finding emerged from a prospective symptom study conducted in the UK, in which British school-aged children were compared for symptomatic COVID-19 courses over different time periods.

Study results coming in earlier this year had already indicated that the Alpha variant of the SARS-CoV-2 virus does not appear to make children more ill than the “wild” form of the virus which first appeared in China. The prospective COVID-19 symptom study, the results of which were published last week, compared two groups of school-aged children with confirmed SARS-CoV-2 infection: 694 children infected with the Alpha variant between late December 2020 and early May 2021, and 706 children infected with the Delta variant between late May and early July.

Disease profiles (prevalence of symptoms, duration and sevon the course taken by the disease. erity), hospitalization and presence of prolonged (≥ 28 days) illness were assessed. In both groups, half of the children were ill for no longer than five days. Although the Delta variant displayed slightly more symptoms than the Alpha, especially in older children, this was offset by a similar duration of symptoms, whether these were considered individually or for the illness as a whole. Furthermore, very few children in either group required hospitalization, and long periods of illness were rare. The study was, however, limited by the lack of information on differences between the groups that might have influenced the results, such as whether lockdowns were in force and the impact of different seasons on the course taken by the disease.

However, the data suggests that the clinical symptoms of COVID-19 caused by the Delta variant in children are broadly comparable to those of the disease caused by other variants. This also appears to be consistent with data from the US Centers for Disease Control and Prevention (CDC). That is to say, although we are seeing more cases in children, the severity of the disease is not increasing. The reason why more children are contracting COVID-19 is mainly because there are more COVID-19 cases in the population as a whole.

The study contributes quantitative information to the debate on whether there are significant clinical differences in COVID-19 due to the Alpha and Delta variants, and to the discussion on whether it is appropriate or necessary to vaccinate children (especially those in the younger age bracket) against SARS-CoV-2. We will continue to monitor developments here, especially with regard to new approvals for the vaccination of children.

Dr Robert Hess: Booster jabs are contributing

Dr Robert HEss

Dr Robert Hess – 10/08/2021

Dr Robert Hess: Booster jabs are contributing to the individualization of the vaccination concept: Weighing up the potential side-effects of the Covid-19 vaccines and deciding the “price” we are willing to pay.

As winter approaches in the northern hemisphere, booster vaccinations are being rolled out with the aim of giving maximum protection to the elderly, the immunocompromised and professionals exposed to the virus. The administration of booster jabs against Covid-19 is a new concept and one that is likely to be with us for the foreseeable future, as the efficacy of the vaccines against Covid-19 wears off over time. According to the manufacturer of the Pfizer/BioNTech vaccine, it loses approximately six percent of its effectiveness every two months, but our experience has shown that this is a conservative estimate.

This is a game changer, as we are no longer dealing with primary protection, but rather with the boosting of immune status which is composed of antibodies, T-cell reactions and much more besides. However, this attempt at maintenance also entails certain risks. Although the documentary evidence for short-term side-effects of booster vaccination does not give cause for concern so far, we cannot yet clearly assess what the cumulative effect of repeated vaccine doses on our bodies might be in the long term. Repetitive vaccination (and we are not just talking about SARS-CoV-2) puts everyone at increased risk of an adverse dose reaction, for example in the form of anaphylaxis. The bioaccumulation of LNPs (= lipid nanoparticles, an adjuvant of the mRNA vaccines, which enclose the RNA and transport it) could also trigger immune reactions, a potential outcome that is becoming ever more relevant with the booster shots.

All of these considerations have to be weighed up against the alternative: absolute renunciation of the booster vaccine could mean accepting the risk of infection with Covid-19 and possible long-term sequelae. There are, of course, no circumstances under which death from Covid-19 is an acceptable risk, but the long-term consequential damage from Long Covid may well be such. Along with permanent optimization of the immune system, vaccination is currently the most potent means of strengthening our immune status.

In summary, we wish to make you aware that, with every vaccine dose you receive, there is a certain “price” to be paid. This can range from minimal side-effects to hypersensitivity reactions, triggering of autoimmune diseases and symptoms of toxicity. How high this price ultimately goes and whether we should consider it reasonable is not always obvious and is a matter for each individual to decide. Depending on age, immune status and various other factors, the recommendation will vary. Our SARS-CoV-2 Task Force will continue to use your data analyses and our A.I. system to advise on the acceptable “price” (i.e. level of risk) for you.

Dr Robert Hess: Corona drug molnupiravir

Dr Robert HEss

Dr Robert Hess – 10/05/2021

Dr Robert Hess: Corona drug molnupiravir significantly reduces number of severe cases of disease and raises hopes, says manufacturer.

Merck Sharp and Dohme (MSD), the US pharmaceutical giant based in Kenilworth, New York, last week reported positive results from a Phase III trial of its new corona drug, molnupiravir. The manufacturer claim that it alleviates the course of the COVID-19 disease and halves the risk of hospitalization or death from a coronavirus infection. The potentially groundbreaking results promise a new way of treating COVID-19 and herald the first of hopefully many more antiviral drugs.

Until now, COVID-19 has been treated with steroids such as dexamethasone and intravenous antibodies (MAB). Both are administered to patients who are already extremely ill. This is not the case with molnupiravir: according to the manufacturer, the medication helps most when it is taken within five days of the onset of symptoms, i.e. in the early phase of the disease.

Molnupiravir has not yet been fully approved, but an Emergency Use Authorization (EUA) from the FDA is expected. Could this antiviral pill bring the world a little closer to normal again?

What is molnupiravir and what are its origins? Molnupiravir was initially developed for the treatment of flu, but has not yet made it to the approval stage for this particular disease. The medication was developed at Emory University in Atlanta, Georgia, in the course of drug discovery research, and in late July 2020, Merck and Ridgeback Biotherapeutics announced plans to study the efficacy of molnupiravir against COVID-19 in trials that would begin in September 2020. On 19th October 2020, Merck then commenced the one-year Phase II/III study of hospitalized COVID-19 patients in the United States.

Molnupiravir itself is a prodrug of N4‑hydroxycytidine, a long-established virustatic agent. As early as the 1970s, scientists were studying the effectiveness of N4‑hydroxycytidine against smallpox viruses. N4‑hydroxycytidine is a ribonucleoside analogue that is inserted into the viral RNA as a “bad” building block, which leads to considerable errors in the copying process with the RNA polymerase (a protein complex that initiates the formation of RNA on the basis of an RNA or DNA template). The mechanism of action is similar to that of the nucleotide analogue remdesivir. However, the effects seem to be more pronounced. The researchers observed lethal viral mutagenesis with catastrophic consequences for the virus (RNA virus error catastrophe). N4‑hydroxycytidine is claimed to be effective against coronaviruses such as SARS-CoV, MERS-CoV and SARS-CoV-2.

What do the results of the trials tell us? The Phase 1 trial of molnupiravir was conducted by the Miami-based manufacturer Ridgeback Biotherapeutics, which had acquired the rights to molnupiravir from Emory University. Molnupiravir was tested on healthy volunteers at a center in the UK at a single ascending dose of 50 to 1,600 mg. No serious adverse events occurred.

Molnupiravir was then tested in a Phase 2 trial on 202 patients who had been infected with SARS-CoV-2 but had only mild COVID-19 symptoms. Patients were given 200 mg to 800 mg of either molnupiravir or a placebo twice daily for five days. At the end of this 5-day period, all patients who had taken tablets containing 400 mg or 800 mg of molnupiravir were virus-free, while the smear test in the placebo group was positive in 11% of patients. As in the Phase 1 trial, molnupiravir was well tolerated. The rate of treatment-induced or serious side-effects was not higher than in the placebo group.

Merck (MSD) has since acquired the license and is currently investigating molnupiravir in multiple international Phase 3 trials at 170 separate centers. The MOVe-OUT trial involved 775 patients displaying mild to moderate COVID-19 symptoms, whose infection had been confirmed no more than five days before. All patients had at least one risk factor for adverse disease progression such as obesity, old age, diabetes mellitus or heart disease. Patients were randomized to five days of treatment with either molnupiravir or a placebo.

An interim analysis in early August found that molnupiravir had reduced the risk of hospitalization or death by around 50%. According to the manufacturer’s press release, this primary endpoint occurred in 28 out of 385 patients (7.3%) in the molnupiravir group as compared with 53 out of 377 patients (14.1%) in the placebo group. There were no deaths in the molnupiravir group compared with eight deaths in the placebo group, so that continuation of the trial was suspended after consultation with the FDA.

What are current expectations? Based on the above results, the manufacturer Merck (MSD) hopes for an emergency approval (EUA) in the near future. Corresponding applications are also to be submitted to other regulatory authorities worldwide. If the medication is approved by the US Food and Drug Administration (FDA), the US government plans to purchase 1.7 million doses.

According to MSD, the company could produce ten million doses by the end of the year. MSD has already entered into licensing agreements with five Indian generic manufacturers, which means that the drug could be made available quickly in large quantities if it is successful.

The latest results from the Phase 3 trial look very promising. The fact that molnupiravir is a drug that is most effective in the early phase of the disease is also a great advantage. We are working on the assumption that the results of the trials will indeed lead to an EUA from the FDA. When this will come is not yet entirely foreseeable, especially since the data have not yet been published and subjected to peer review.

We will continue to keep an eye on what is happening and keep you informed about this. We will also find out when the drug would be available at the earliest and whether it might make sense to be able to have access to it in the event of an infection. Depending on your personal situation, we will contact you again individually as soon as this drug is approved.

Dr Robert Hess: Current status and news of new concepts

Dr Robert HEss

Dr Robert Hess – 09/16/2021

Dr Robert Hess: Current status and news of new concepts such as antibody therapy and vaccination by inhalation against COVID-19 infection.

Dr Robert Hess has a special interest in this topic, because for some of our premium members the conventional vaccination against Covid-19 is not an option or even can be counterproductive. We see these new concepts as possible solutions for additional protection against coronavirus infection without the need for vaccination.

In certain cases, monoclonal antibodies (MAK) are considered to be a promising drug against severe disease progression in SARS-CoV-2 infection and have been used in the clinical setting for some time. In this context, we are particularly interested in the question of whether and, if so, when antibody therapy might also be used in the context of prophylaxis against a covid infection.

What exactly are monoclonal antibodies (MAK)?

Monoclonal antibodies (MAK) against the SARS-CoV-2 coronavirus are proteins of the immune system that have been biotechnologically engineered to dock to specific surface structures of the SARS-CoV-2 coronavirus. The engineered antibodies bind structures on the coronavirus or block receptors on human cells, preventing SARS-CoV-2 viruses from entering human cells. MAK-containing drugs may also contain combinations of multiple monoclonal antibodies. Monoclonal antibodies were previously only intended as drugs for early therapy in persons infected with SARS-CoV-2 at risk of a severe course, but in August of this year, the FDA approved the first monoclonal antibody therapy for post-exposure prophylaxis as part of the emergency use authorization (EUA).

The FDA revised the EUA for REGEN-COV, which consists of the monoclonal antibodies casirivimab and imdevimab administered together, authorizing REGEN-COV for emergency use as post-exposure prophylaxis (prevention) for COVID-19 in adults and adolescents (12 years of age and older) who are at high risk of progression to severe COVID-19, including hospitalization or death. It remains the case that REGEN-COV has not been authorized for pre-exposure prophylaxis to prevent COVID-19 (i.e. before being exposed to the SARS-CoV-2 virus) – only after exposure to the virus. REGEN-COV was already approved earlier this year for the treatment of mild-to-moderate COVID-19 in adults and adolescents (12 years of age and older) who have tested positive for SARS-CoV-2 and are at high risk of progression to severe COVID-19, and it remains authorized for that.

The FDA emphasizes that prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19. REGEN-COV may only be used as post-exposure prophylaxis for adults and adolescents who are:

– at high risk of progression to severe COVID-19, including hospitalization or death, and

– not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, people with immunocompromising conditions, including those taking immunosuppressive medications), and

– have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria or

– who are at high risk of exposure to an individual infected with SARS-CoV-2 because of other individuals in the same institutional setting becoming infected with SARS‑CoV‑2.

How is close contact to an individual infected with SARS-CoV-2 defined?

The CDC defines close contact as someone who has been within six feet of an infected person (laboratory-confirmed or a clinically compatible illness) for a cumulative total of 15 minutes or more over a 24-hour period.

What are the possible side effects of receiving a treatment with monoclonal antibodies, such as REGEN-COV?

The most common side-effects were injection site reactions. The signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were skin redness (erythema), pruritus, and ecchymosis (discoloration of the skin resulting from bleeding underneath, caused by bruising). There were no cases of severe hypersensitivity reactions, or potentially life-threatening allergic reactions such as anaphylaxis.

Vaccination by inhalation:

Inhaled vaccines aren’t unheard of — they exist for other viruses such as flu. But they are a relatively new technology, arriving on the market in the early 2000s. The Covid-19 pandemic, however, requires the largest mass-vaccination campaign in history, which means all options need to be on the table for first-round vaccines and any boosters that may be required. Inhaled vaccines should be easier to administer as well as being more accessible and are claimed to have fewer systemic side-effects.

There are currently several research facilities and drug companies testing and evaluating possible intranasal and inhaled COVID-19 vaccines. CanSino Biologics, a Chinese drug company; just finished their phase 1 clinical trial on the world’s first aerosolized adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) and announced its safety and effectiveness after administration of two doses. Phase 2 clinical studies of the vaccine are ongoing.

In the UK, scientists at the University of Oxford have begun phase 1 clinical trials on 54 healthy adults to investigate intranasal vaccination with Covishield following positive findings from studies done on hamsters, while Codagenix, a biotech startup, is currently evaluating a novel inhaled COVID-19 vaccine candidate called COVI-VAC in phase 1 clinical trials involving 48 participants. COVI-VAC is a single-dose, intranasal, live-attenuated vaccine against COVID-19. Unlike many other COVID-19 vaccines, COVI-VAC is designed to produce immunity against all SARS-CoV-2 proteins, not just the spike surface protein, positioning it to protect against a range of SARS-CoV-2 strains.

And in the US, the startups Phage Novo Bio and Precision Virologics have also shown through animal trials that their inhaled candidates for Covid-19 vaccines were safe and effective. In a new study assessing the potential of a single-dose intranasal COVID-19 vaccine, a team from the University of Iowa found that the vaccine fully protects mice against lethal COVID-19 infection. The vaccine also blocks animal-to-animal transmission of the virus.

So far, all of the inhaled Covid-19 vaccine candidates are either in the animal testing phase, or the first stages of clinical trials testing the safety and effectiveness of these sprays in a small group of healthy people. We can therefore only provide an overview of this topic but will continue to keep an eye on what is happening. The publications and findings to date seem promising. Ordinarily, it can take years for vaccines to go from early clinical trials to the market. At the moment, drug regulators have accelerated the authorization process by laying out the exact kinds of data companies need to generate to prove their products are safe and effective. The urgency of vaccinating the world may keep these high-speed processes in place to get the much-needed approvals.


Dr Robert Hess: Update on new mutations

Dr Robert HEss

Dr Robert Hess – 09/14/2021

Dr Robert Hess: Update on new mutations and what you need to know about COVID-19 variants.

As experts in the field of human and molecular genetics and thus also on the topic of mutations, we provide regular updates and forecasts of where the pandemic might be heading. Recently, new discoveries have come into the frame, so we have summarized these findings for you and added our own assessment.

Several thousand COVID-19 variants exist around the world, but most of them do not change the way the virus acts. So far, only a few mutants have evolved from the original strain that have given the virus an advantage and accelerated the course of the pandemic. Experts are constantly working to figure out which variants we should focus on and how they change the way in which we combat COVID-19. At the moment, there are only a handful of COVID-19 variants that give us cause for concern. The current “variants of concern” (VOCs) all have mutations in the virus’s spike protein, which acts as a key to break into cells and infect them. This is a source of concern because the spike protein from the original version of the virus is what the scientists have used to design all three authorized vaccines. It is also what monoclonal antibody treatments latch on to so the virus is unable to get into your cells, effectively neutralizing the threat. So far, none of these mutations have changed the virus enough to undercut the vaccines. The current VOCs listed by the WHO are Alpha, Beta, Delta and Gamma SARS-Cov-2 variants.

The Delta variant is our biggest concern at the moment. Identified in India in October 2020, it gained dominance quickly after it was first reported in the U.S. in March 2021. In fact, Delta has now spread to such an extent that it has splintered into several subvariants, referred to as “Delta plus”. Delta plus variants have a mutation in the spike protein found in both the Beta and Gamma variants that may help to evade neutralizing antibodies. While around 13% of infections in the U.S. are from Delta plus variants (AY.1, AY.2, and AY.3), they still behave similarly to the Delta variant. The AY.3 subtype is one of the most recent descendants of Delta but among the most notable. Experts suspect that it is potentially better at escaping the immune system. The variant is most dominant in the US where it makes up roughly 9% of all cases. Along with AY.1 and AY.2, it is now also a variant of concern (VOC). Together, the Delta lineages make up 80-95% of sequenced infections in the U.S. Like other VOCs, Delta has multiple mutations in its spike protein. What makes Delta unique is that it is much more efficient at latching onto your cells and is much more contagious. As already stated, Delta is about twice as infectious as the original strain and estimated to be 60% more infectious than Alpha. People infected with the Delta variant have been reported to have viral loads 1,000 times higher than other variants. Besides the above, five variants of interest (VOI) are currently (as of 09/07/2021) listed and followed with special attention: Eta, Iota, Kappa, Lambda und Mu. While the first four have been under special observation for at least one and a half months, Mu was only classified as a variant of interest by the WHO towards the end of August 2021 due to outbreaks in Europe and increasing infections in Colombia and Ecuador, where the Mu variant is responsible for 39% and 13% of COVID-19 infections. Mu was first sequenced in Colombia in January 2021. So far, it has been documented in 39 countries, including the U.S. However, the percentage of COVID-19 cases triggered by the Mu variant in the U.S. has been falling since July, and the Mu variant caused only about 0.2% of COVID-19 infections in the country in the week of 20th ‑ 27th August. What worries scientists is that the Mu mutations could indicate possible resistance to vaccines. Early research from Italy shows Mu is susceptible to antibodies produced by the Pfizer-BioNTech vaccine, but they don’t work as well as they do against the original Wuhan strain or Alpha variant. In addition, the combinations these mutations indicate a risk of immune resistance. Early research from the U.K. found the specific mutations may help Mu escape the immune system. Further studies are needed for an accurate assessment.

While much of the world’s focus has been on the Delta variant of coronavirus, a new variant was identified in South Africa in May 2021. Currently referred to as the C.1.2 variant, it is yet to be called a VOI or VOC by the WHO, but is drawing the attention of scientists due to the number and types of mutations it contains and the speed at which the mutations have occurred. With 59 detected mutations, C.1.2 is reported to be the variant carrying the most mutations since the original “wild” variant emerged in China. The variant has emerged from the C.1 lineage which was one of the coronavirus lineages that dominated during the first wave of infections in South Africa in mid-May 2020. Although levels of the C.1.2 variant are still low among the South African population, it remains a concern to local public health experts and scientists across the world. Currently, Delta remains the dominant variant in Europe, the U.S. and much of the world. For a variant to become dominant it will have to outcompete Delta. That will mean increased transmissibility, being able to bind to human host cells and infect people quicker than Delta currently does. Time will tell whether any of the variants mentioned here will prevail against Delta and, if so, to what extent. The WHO, public health experts and scientists will continue to closely monitor the course of events. We will also continue to keep you informed about any news on this front.