Prof Carl Heneghan & Tom Jefferson

Something rather odd is happening in the two Europeans nations worst hit by Covid-19. The UK and Italy have a rising number of cases but a stable and very low number of deaths, even weeks after the cases started rising again.

At the time of writing, the UK records 1750 new cases daily and one death in a population of 67 million. With a roughly similar population and an average of 602 cases a day, Italy has had just over four deaths a day over the last month. The ratio of cases to deaths is nowhere near what it was at the height of the pandemic. The other notable feature is a shift of cases to a younger population.

UK: Covid tests vs hospital cases

There can be several explanations for this trend. First, the viral agent may have mutated to a less virulent form. Although there are some published studies showing minor mutations, these are what you would expect from an RNA virus which is inherently unstable (think of the influenza viruses, which perpetually change their suits).

Second, we may have got better at dealing with Covid-19. Apart from dexamethasone in the small population admitted to intensive care units, there are no specific treatments for the disease, and as we are not observing a substantial increase in admissions or severity of the disease, this seems also an unlikely explanation.

Third, our preventive measures may have worked, only allowing new cases when lapses have occurred. If this were the case we would expect effectiveness against all forms of acute respiratory infections, like the winter illnesses. This has indeed happened in the Southern hemisphere, but the age shift does not fit with this theory.

A fourth possible and much more complex explanation is what we call the ‘reality problem’. There is rapidly accumulating evidence that the tests used worldwide to identify cases in a binary mode ‘Yes or No’ are being used in a simplistic and uncoordinated way. We have already explained the limits of polymerase chain reaction (PCR) to carry out mass testing.

PCR is a very sensitive test, which means that it detects the smallest fragments of the virus it is looking for by amplifying the sample millions of times. However, a fragment is not a whole virus, capable of replication and of infecting other human beings. It is a small part of the viral structure that the PCR primer is looking for, not the whole microorganism. Only whole viruses can infect us.

In addition, the number of amplification cycles necessary to reach a ‘positive test’ is rarely reported. We now know that his is a vital piece of information in interpreting results. A very high number of cycles may detect fragments and give a positive result but a lower number of cycles is far more likely to identify infected and infectious individuals requiring quarantine.

You would expect all of this to be reported in a PCR results but it is not routinely done. There is worse news to come. A very sensitive test is vulnerable to contamination with extraneous genetic material (hence the need for suiting up operators). The rapid expansion of testing capacity may have degraded our capacity for sterility by increasing throughput and straining lab staff training. We also have come across studies looking at the different performance of PCR kits on the same sample and the results are not encouraging, with wide variation in cycle thresholds for the same positive results indicating the absolute requirement to standardised tests worldwide continuously comparing procedures and performance of testing against the only real gold standard for gauging a person’s contagiousness: viral culture.

Evidence is mounting that a good proportion of ‘new’ mild cases and people re-testing positives after quarantine or discharge from hospital are not infectious, but are simply clearing harmless virus particles which their immune system has efficiently dealt with. Those whose immunity is more active are exactly in the age group of observed ‘positives’ and least likely to end with severe disease.

So, we appear to have the reality of viral circulation, probably waning fast and the perceived reality of a misused and simply interpreted genial test which can be used to great effect when viral circulation is far higher (making it more likely a positive test correctly identifies the virus) or in finding traces of bugs which are good at hiding in our bodies, or their fragments in waste waters indicating their presence at some time in the past.

To avoid this dual reality and the dangers of isolating non-infectious people or whole communities we need an international effort to standardise testing, periodic calibration against culture or other recognised measures of infectiousness and strict laboratory protocols and procedures probably with a central licensing authority. A lot more work needs to be done to correlate cycle thresholds, patients’ characteristics and intelligence on virus circulation. Medicine and public health are about people, not printouts.

The scientists discovered that, despite people with Covid-19 being infectious for only around a week, one test used to detect the disease can still give a positive reading weeks after the patient has recovered.

WRITTEN BY

Prof Carl Heneghan & Tom Jefferson

Carl Heneghan is professor of evidence-based medicine at the University of Oxford and director of the Centre for Evidence-Based Medicine Tom Jefferson is a senior associate tutor and honorary research fellow at the Centre for Evidence-Based Medicine, University of Oxford

via Sputnik

Leading international scientific journal The Lancet has published the results of the first two stages of clinical trials for the Russian COVID-19 vaccine.

Sputnik has spoken to the vaccine developers at the Gamaleya Centre, Alexander Gintsburg and Denis Logunov, as well as the CEO of the Russian Direct Investment Fund Kirill Dmitriev, to find out what data the article cites and why it is so important for the global scientific community.

Today, less than a month after the Sputnik V COVID-19 vaccine was registered, the world’s most influential scientific journal The Lancet has published the results of the first two stages of clinical trials, so highly-anticipated by both the Russian and international scientific community.

The article responds to foreign criticism and provides long-awaited clarity. The Russian scientists’ development, which turned out to be the world’s first registered coronavirus vaccine, is not only effective but safe.

Start of a Series of Publications

The Lancet has published the results of the first two stages of clinical trials and, according to the vaccine developers at the Gamaleya Centre, this is going to be the first step towards a series of publications about the Sputnik V vaccine in scientific journals.

“In September, a complete study of the vaccine in animals, primates, Syrian hamsters, transgenic mice, in which the vaccine has shown 100% protective efficacy (results in primates and Syrian hamsters were obtained before clinical trials), will be published. The first results of the ongoing post-registration clinical trial involving 40,000 volunteers will be published in October-November”.

‘Vaccine With Proven Safety’

The Sputnik V vaccine’s safety is one of the main conclusions cited in the article. According to the first and second-stage clinical trial results, the scientists didn’t find any serious adverse effects from the vaccine regarding any of the evaluated criteria. Not all candidate vaccines can boast of such results, some have noted up to 25% experiencing serious adverse effects.

Long-Term Immunity

The Lancet also cites scientific evidence of the Sputnik V vaccine’s effectiveness. For example, evidence of the treatment’s ability to launch a long-term immune response to the coronavirus in 100% of those vaccinated due to its unique two-stage introduction technology. According to Denis Logunov, deputy research director at the Gamaleya Centre, a humoral and cellular immune response, which is enough to protect a person from COVID-19, has been observed in 100% of those vaccinated.

“The antibody levels in vaccinated volunteers was 1.4-1.5 times higher than in those who had recovered. For reference, Britain’s AstraZeneca vaccine showed an antibody level roughly equal to the antibody level in those who had had the coronavirus infection”.

Scientists at the Gamaleya Centre confirm that in the context of Sputnik V clinical trials, all of the volunteers developed T-cell immunity, represented by both CD4+ and CD8+ cells, making it possible to recognise and destroy coronavirus-infected cells.

‘The Vaccine Will Work in 100% of Cases’

One of the scientific community’s biggest fears regarding the use of human adenoviral vector vaccines — the technology used in Sputnik V — was the pre-existing immunity to adenoviruses in some people.

In other words, there was a concern that our immunity might not allow the required amount of human adenovirus into the body. This serves as a kind of “taxi” in the vaccine, delivering the outer shell genetic material of the coronavirus into the cells (it’s important that the coronavirus itself doesn’t enter the body with the vaccine, which completely eliminates the possibility of infection).

Due to people often getting sick with adenoviruses (like the common cold), they could have developed immunity, which theoretically could reduce the adenovirus vaccine’s effectiveness. However, the results of the trials presented by the Gamaleya Centre scientists prove otherwise: pre-existing immunity doesn’t affect the vaccine’s effectiveness.

“We’ve chosen the optimal safe dosage, providing an effective immune response in 100% of those vaccinated, including those who have recently had adenovirus infections. This reduces the urgency of developing new vaccines based on untested platforms”.

According to the representatives of the Gamaleya Centre, what is meant by unverified platforms are developments of some Western companies, that started out of concerns regarding human adenoviruses. Some of these developments, such as mRNA technology (Moderna’s vaccine) or chimpanzee adenovirus (AstraZeneca’s vaccine), have never been used to create registered vaccines.

Such drugs need long-term testing because of concerns regarding their effect on the body’s reproductive functions or the possible high carcinogenic properties that lead to cancer, the centre concluded.

In the article, Russian scientists refer to studies about the safety of the platform on which the Sputnik V vaccine is based.

“Since 1953, more than 250 clinical trials have been carried out globally, and more than 75 international articles have been published confirming the safety of vaccines and drugs based on this platform”, Denis Logunov explained.

“Human adenoviral vectors-based drugs have been used for over 15 years. In particular, these are Ebola vaccines and the anti-cancer Gendicine, which has been used in China for over 12 years”.

Unique Two-Vector Technology

According to Alexander Gintsburg, Sputnik V’s unique feature is using two adenoviruses, serotypes 5 and 26, in two separate vaccinations. Today, many experts recognise double vaccination as a factor that can significantly enhance immunity to the coronavirus.

However, if the same vector is used for two vaccinations, the immune system triggers defence mechanisms and begins rejecting the second-injection drug. This problem is solved by using two vectors in Sputnik V, which helps avoid the described neutralising effect.

Gamaleya vs AstraZeneca

Responding to criticism about the insufficient number of volunteers for the two-vector vaccine, the scientists recalled that they managed to test this system on a wider range of people than, for example, one of the leading vaccine candidates, AstraZeneca, did.

The British pharmaceutical giant used four times fewer volunteers during the first two trial stages to determine their two-vector vaccine’s effectiveness.

“The number of volunteers involved in testing the Russian Sputnik V vaccine during stages 1 and 2, carried out with two injections, was 4 times higher than the number of people AstraZeneca involved”, Kirill Dmitriev said.

‘The Only Safe Technology’

Last week, the US Food and Drug Administration announced the possible use of accelerated registration for vaccine candidates due to the current epidemiological situation, without a third phase of clinical trials on tens of thousands of volunteers.

The British authorities also spoke about the possibility of a similar approach. At the same time, according to these countries’ regulators, accelerated registration will only be possible for vaccines that have already proven their effectiveness and safety.

According to Russian specialists, there are not very many drugs that meet these requirements.

“To date, the only one meeting these criteria is a human adenoviral vector platform. It has proven its safety through several decades of numerous studies”, Kirill Dmitriev said.

The Lancet Publication is the ‘Final Answer’

Kirill Dmitriev, CEO of the Russian Direct Investment Fund, explained that The Lancet’s publication of the clinical trial results is “the final answer in the round of questions directed against Russia” following the Sputnik V’s registration in August.

“In turn, Russia can now ask some questions to the international community. We are calling to publishing official data that would prove the long-term efficacy of chimpanzee adenovirus or mRNA-based vaccines, the absence of any carcinogenic risks and effects on fertility when used. We would also like to know why AstraZeneca is pushing for a legal disclaimer for unwanted side effects”.

By Peter Andrews, Irish science journalist and writer based in London. He has a background in the life sciences, and graduated from the University of Glasgow with a degree in genetics

It has been revealed that the standard tests being used in the US to diagnose Covid-19 cases are far too sensitive, with the vast majority of people marked down as being positive actually turning out to be negative.

Top US virologists have been stunned by revelations about the laxity of the US Covid testing regimen. It turns out that tests that deliver a simple binary“positive or negative” result are not fit for purpose, as they tell us nothing about the contagiousness of each person.

Data from three US states – New York, Nevada and Massachusetts – shows that when the amount of the virus found in a person is taken into account, up to 90 percent of people who have tested positive should actually have been negative, as they are carrying only tiny amounts of the virus, are not contagious, pose no risk to others, and have no need to isolate.

This means that only a fraction of the daily “cases” being reported so hysterically in the mainstream media are actual, bona fide Covid-19 sufferers, and need treatment and to separate themselves from others.

It’s a sensitive issue

So how could this have happened? The answer has to do with the sensitivity of PCR (Polymerase chain reaction) tests for Covid, which it turns out can be ramped up according to the taste of the testing companies. Most testing companies have chosen the outrageously high sensitivity limit of 40 PCR cycles – meaning that the DNA in a sample is exponentially increased 40 times in order to amplify its signal.

Just wait for a vaccine? First confirmed REINFECTION means there may be no way to eradicate Covid

But using such a ridiculously sensitive test means that the faintest traces of a dead virus, or even leftovers from previous infections, can result in a positive. Professor Juliet Morrison, a University of California virologist, said that even a limit of 35 PCR cycles is too high, let alone 40. She said she was “shocked that people would think that 40 could represent a positive.”But apparently, pretty much everyone in the US Covid brain trust took exactly that on faith.

So the scale of the pandemic ‘problem’ is actually much smaller than we’ve been led to believe – about a tenth of what all the politicians and media have been using to justify the lockdowns, the quarantines, the mass testing. Some may be shocked that the scale of the problem is so much smaller than assumed. But for a seasoned ignorer of any and all statistics that contain Covid ‘cases’, there are no surprises here. The truth is, there was never any reason to be confident in such figures. The FDA has only now been forced to concede that they have no idea how different testing companies determine which the positive and negative tests are: they just accept whatever data they are given.

What these findings bring is absolute assurance that the testing to this point has been an utter waste of time, and that not one statistic concerning this pandemic – from cases to deaths to infection rates – can be believed. But it should not have taken some journalist to ask the right question to discover this: a bit of common sense would have been enough. What is it going to take for these professional virologists to drop their assumptions and models, and just start acting based on the facts at hand?

Scrap test and trace

It’s a virus so deadly, you need a test to tell whether you have it or not. So goes the refrain of many lockdown skeptics, Covidiots and anti-maskers, of whom I am an indignant supporter. Something has gone… not just wrong, but totally haywire… when the might of the world’s scientific establishment is trained with the zeal of a Witchfinder General on one particular microscopic particle. Not even a particularly dangerous particle; the latest data show it is the eighth most common cause of death in England, and it doesn’t make the top ten in Wales.

Meanwhile, in Wuhan, the original source of this disease, the pool partiesare in full swing. They don’t seem to be too worried about PCR tests or contact tracing, or even the virus itself. The Chinese government says that their supreme lockdown was so awesome that they now have zero Covid: a biological impossibility. Maybe they just stopped testing, and decided to get on with their lives. Everyone else should take a leaf out of their book.