Prof Noakes Responds: The cause of the “silent” hypoxia in severe COVID-19 infections and the value of hydroxychloroquine in the treatment of COVID-19 infections
Nathan Geffen PhD gets it wrong. Again.
by Emeritus Professor Timothy Noakes OMS, MBChB, MD, DSc, PhD (hc).
I wish to respond to the recent article by Dr Nathan Geffen PhD re-published in The Daily Maverick (1).
- Dr Geffen’s 2014 article.
This is the second time that Dr Geffen has disparaged me publicly. His most recent article follows the identical approach of a previous article of August 28th 2014 (2): the similarities are instructive. Both articles were distributed seamlessly and instantly through his well-oiled networks in the social, print and broadcast medias. Which reminds one of Jonathan Swift’s famous quote: “Falsehood flies, and the truth comes limping after it; so that when Men come to be deceiv’d, it is too late; the Jest is over, and the tale has had its Effect” (Jonathan Swift: The Examiner, 1710).
In his 2014 article (2) Geffen accused me, as he does now, of “spreading a dangerous claim”. His 2014 article spread the malicious falsehood that I am “anti-vax”. Through his efforts, that falsehood is now irrevocably embedded in Wikipedia.
But Geffin knows that I am not “anti-vax”. I received the regular childhood vaccines as did my children and grandchildren. I have never advised the general public to refuse vaccinations. On Twitter I have repeatedly stated that vaccination is one of the great achievements of modern medicine; a discovery that has saved millions of lives.
So on what basis did Geffen fabricate this particular falsehood?
The origin of his fabrication was a Tweet I posted in 2014. The Tweet drew attention to a recently released YouTube video which included allegations of scientific fraud within the Centre for Disease Control (CDC) in Atlanta Georgia. A whistleblower, subsequently identified as Dr William W. Thompson PhD (3), alleged that the CDC had suppressed evidence showing that male African-American children who received the triple Mumps Measles Rubella (MMR) vaccine before 3 years of age were at a 3.86 fold increased risk of developing autism compared to other male children of other ethnic groups (Table 3 in reference 4). The evidence proving these allegations to be correct has since been published in a peer reviewed journal, the Journal of American Physicians and Surgeons (4). Thus my original Tweet conveyed information that has since been proven to be factually correct. It is difficult to understand how factually correct information can be “dangerous”.
Indeed the author of that paper expressed his regret at the long-term consequences of the fraud that the CDC scientists had committed: “The data set used by DeStefano et al. (5) represents a huge lost opportunity to understand any role between the timing of the first MMR vaccine and autism. This re-analysis presented here elucidates effects that should at least merit further investigation. Specifically, increased risks of earlier vaccinations are observed for African-American males and among cases of autism without MR (Mumps Rubella). Both phenomena deserve additional study that could yield important clues regarding the current enormous increase in autism” (4, p.109).
(Note that the Whistle blower, Dr William Thompson PhD is a listed author of the false DeStefano et al. scientific paper (5). Thompson’s admission incriminated himself as a party to the cover-up).
Yet my Tweet was not about vaccine safety. The Tweet simply asked whether this was another example of “Bad Science”. That is why the Tweet was posed as a question and ended with a question mark. The focus of the Tweet was “Bad Science”; it just happened to involve the suppression of what proved to be legitimate findings relating to vaccine safety.
Yet Geffen manipulated that real meaning of the Tweet to serve his own dishonest purposes. From a Tweet on Bad Science he produced a litany of accusations (2). He accused me of a “flirtation with the anti-vaccination movement (that) can’t be ignored. Here is an academic with a considerable public voice and masses of supporters spreading a dangerous claim” (2, p.2)”. “After recommending that his followers watch videos that cast suspicion on the MMR vaccine, it is disingenuous for Noakes to say he has no opinion”. “To spread doubt about the vaccine as he has done is not merely arrogant, it is irresponsible” (2, p.2-3).
Again to re-iterate my focus was on Bad Science, not whether or not the MMR vaccine is associated with autism in a particular group of susceptible infants.
In the article, Geffen expresses his certainty that there was absolutely no possibility that the CDC could ever be involved in a cover-up; any such claims are just an obvious conspiracy theory: “The claims made in the videos (sic) have been debunked by David Gorski on his website…There is no evidence of a CDC cover-up, nor any evidence that the MMR vaccine causes autism….In reading Gorski’s superb article you’ll find there’s a troubling racial angle to the conspiracy theory (my emphasis) too. The anti-vaccination proponents are claiming that what is being covered up is a statistical association between the MMR vaccine and autism in black children. This is nonsense; no such association has been found” (1, p.2).
It is interesting that investigative journalist Geffen ignores the elephant in the room – that the CDC has a massive financial conflict of interest: “The CDC is the largest single buyer and distributor of vaccines in the United States” (6, p.5).
What is interesting is that even though the evidence disproving Geffen’s false claims has now been in the public domain since 2018, Geffen has made no effort to correct the falsehoods contained in his 2014 article.
My understanding is that a responsible journalist is ethically bound to correct any factual errors that he had reported and which could have serious long-term health consequences for many. After all, Geffen’s case against me is that I am guilty of exactly that: Expressing dangerously incorrect opinions that could impact the health of millions.
So now it’s Geffen’s turn to correct his “dangerously misleading” claims.
And when he does finally summon up the courage to publish a full apology for that article in his self-published online magazine Groundup – his retraction of the article would be even better – I wonder if he would also explain why he, a young man in a distant country, felt compelled to defend a major US Government agency by choosing to shoot me, an inconvenient messenger?
Also, in his article vaccine-activist Geffen refers to the work of Dr Andrew Wakefield whose “name has become synonymous with dishonesty in science”. Yet, whatever is the truth of that allegation, the reality is that Wakefield’s original paper apparently “fatally flawed both scientifically and ethically” according to Geffen, nevertheless was the first to identify the findings that the Hooker paper (4) has now confirmed. Perhaps Geffen might at the same time also apologize to Dr Wakefield.
Now that we understand how Geffen’s mind functions, we can move on to a detailed exposition of his more recent attempt to discredit me.
- Dr Geffen PhD has no training in medicine, virology, pharmacology, physiology, or in any of the biological sciences. Yet he believes that he is sufficiently expert in all these topics to offer definitive answers to his audience.
The main focus of Geffen’s criticism is that I am not sufficiently expert to offer any opinions on the COVID-19 phenomenon. Yet, if I am not sufficiently expert to offer any opinions, where does that leave Geffen? Geffen’s training is in Computer Modelling with a particular interest in HIV/AIDS for which he has received the PhD degree. He has absolutely zero training in the topics that I discussed in the radio interview on which his recent article is based.
On the other hand I have taught physiology to medical and science students for more than 35 years and during my career was an National Research Foundation A1 rated scientist, indicating an undisputed world leader in two areas – sports science and nutrition. And it was on those two specific topics that I focused my key comments in the interview. Importantly it was only those two topics which offer novel insights into how the COVID-19 pandemic is challenging aspects of modern medical practice.
The other topics I discussed were background information. Whether they are right or wrong has no bearing on what was the main message of the interview.
- The two topics on which I focused in the radio interview: (i) The “silent” hypoxia of COVID-19 that is best treated by avoiding invasive ventilation (IV), and (ii) Persons with the insulin resistance syndrome are especially liable to a fatal outcome from this viral infection.
Those two topics on which I focused in the interview were: (i) What is now called the “silent” hypoxia (7) that develops in persons in the early stages of the COVID-19 infection, and (ii) the clear evidence that persons with metabolic disease, in particular insulin resistance and its associated conditions – obesity, hypertension, type 2 diabetes mellitus and coronary heart disease – are at greatly increased risk for severe COVID-19 infections (8-15).
Predictably Geffen evades any discussion of this second point because he knows that what I said in the interview has exposed an inconvenient truth: That the COVID-19 pandemic is as much about a viral pandemic as it is about a pandemic of human metabolic ill-health produced by the dietary advice we have been receiving since 1977.
For the evidence is very clear that it is the current Dietary Guidelines that have caused the global obesity/diabetes/metabolic syndrome pandemic that is the ultimate feeding ground on which this virus thrives. And the reversal of the obesity/diabetes/metabolic syndrome requires that humans alter their diets in favour of the one that I have been advocating for the past 10 years.
But Geffen has been vigorously opposed to my promotion of that diet, beginning from its inception with the publication of the Real Meal Revolution in 2013: “Noakes’ dietary advice is highly controversial….”; “Sensational media headlines followed his recent visit to Parliament where he reportedly told MPs (that) South Africa ‘was sitting on a time bomb if diabetes and obesity were not addressed’. That’s a somewhat misleading statement, but beyond the scope of this article” (2, p.2).
Well perhaps that “time bomb” has now finally exploded? Perhaps if populations and governments had paid more attention to this issue of metabolic health, the current lockdown might not have been so necessary?
But let us return to the “silent” hypoxia that develops in this pneumonia associated with fulminant COVID-19 infections. Am I enough of an “expert” to venture an opinion on the topic of hypoxia?
My training in exercise science began in the 1970s when it was “known” that human exercise performance is limited by hypoxia (reduced oxygen partial pressure) in the exercising skeletal muscles (16). Over the next 30 years my team and I disproved this (17-21) and replaced it with what is now considered a more probable explanation that does not involve skeletal muscle hypoxia (22,23). Rather we provide the evidence that during exercise, the brain generates the symptoms of fatigue to ensure that the exercise terminates before hypoxia can occur.
Importantly this work superseded an established dogma (16) that had been believed as established fact for more than 100 years. It also explained for the first time a phenomenon that has been observed for at least as long but the elucidation of which had escaped generations of exercise scientists – the Lactate Paradox of High Altitude Hypoxia (17-19).
This body of work is considered one of two seminal contributions I made to world science and was part of the reason why I was awarded a DSc degree, the highest such award, by the University of Cape Town in 2002.
So I suspect I am rather more qualified than is Geffen to discuss the “silent” hypoxia that is one of the key defining features of fulminant COVID-10 infections.
My interest in the pathophysiology of COVID-19 infections was sparked by a YouTube presentation (22) by Clinical Care and Emergency Medicine specialist Dr Cameron Kyle-Sidell MD, then working at the Maimonides Medical Centre, Brooklyn, New York.
In his self-produced presentation, Dr Kyle-Sidell was clearly pleading for help and more understanding. He wanted to bring the world’s attention to a clinical phenomenon he had observed and which was causing him great distress. So in his desperation, he had turned to social media for assistance.
In this and subsequent presentations Dr Kyle-Sidell explains the problem that he faces as an intensive care physician treating patients with COVID-19 infections according to the protocols then in place for the treatment of Acute Respiratory Distress Syndrome (ARDS). Importantly patients then under his care would, when he recorded the video a few weeks ago, were classified as suffering from COVID-19 ARDS.
The protocols then in place for the management of ARDS and to which, as a practicing critical care intensivist he is medico-legally bound, was that any patient under his care who presented with a diagnosis of ARDS must be placed on a ventilator – so called invasive ventilation (IV) – immediately that patients’ blood oxygen content falls below a certain value.
Kyle-Sidell’s concern was that once the blood oxygen content of patients with conventional ARDS reaches levels requiring IV, they are usually semi-conscious. Which makes intubation possible without pharmacologically-induced coma, since the semi-conscious patient is less likely to resist the passage of a tube through the mouth, down the throat and into the windpipe so that IV can be performed.
So the problem Kyle-Sidell identified was that a large number of patients with COVID-19 ARDS and whose blood oxygen content was sufficiently low that the ARDS protocol mandated IV, were fully conscious – they were suffering from “silent” hypoxia as also described by Levitan (7) – and were able to converse with him or even their friends with cell phones. But in order to adhere to the medico-legal requirements of the ARDS protocol, Kyle-Sidell was legally obliged to use pharmacological agents to induce a state of semi-consciousness in these patients before he could perform IV.
With time he became increasingly unwilling to do this. Especially when he began to notice that most of the patients treated with IV did not survive (as subsequently confirmed (9)).
In his presentations Kyle-Sidell postulates that the conscious patients with COVID-19 pneumonia he was treating are “silently” hypoxic, not solely because they have a pneumonia that requires IV according to existing ARDS protocols. Instead his experience is that such patients are more likely to survive if they are given 100% oxygen at very high flow rates through some or other facial mask that does not require IV. In essence he was saying that treating COVID-19 lung infections as if the condition is identical to ARDS does not address the core problem which appears to be more than only a potentially life-threatening lung infection.
At the same time that Kyle-Sidell was describing his dilemma, Professor Luciano Gattinoni at the University of Gottingen in Germany, was observing that patients diagnosed with COVID-19 ARDS could be separated into two distinct groups, or phenotypes (23-25). Figure 1 lifted from the internet shows a key difference between the two phenotypes.
Figure 1 shows the computerized tomography (CT) scans of the chests (heart and lungs) of two patients presenting with breathing difficulties as a result of COVID-19 infections.
The left panel shows the lung involvement detected in the majority of patients (~70-80%) who present to hospital with breathing difficulties and “silent” hypoxia as a result of COVID-19 infections (Type L lung involvement); the right panel (Type H lung involvement) is the much more severe involvement found in 20-30% of these patients.
There are two key points that according to Professor Gattinoni, make this division into two separate phenotypes essential. First he discovered that the mechanical functioning of the lungs of Type L patients was barely compromised. In contrast the mechanical functioning of the lungs of Type H patients was severely affected. Yet the impairment of oxygen delivery to the blood, measured as the blood oxygen content, was not as dissimilar as their lung CT scans suggested it should be.
Second, Gattinoni argued that Type L patients did not require IV. In fact they were much more likely to survive if they were not put on a ventilator. Which was essentially what Kyle-Sidell had suggested in his YouTube presentation.
When I saw Dr Kyle-Sidell’s presentation I was sufficiently certain that he was correct. To share his hypothetical opinions to a wider audience I decided to re-tweet any material that he provided. In one such Tweet I suggested that Kyle-Sidell’s message sounded just as important as that of Professor Ignaz Semmelweis, 180 years earlier (26), but in a different context.
Whether or not those Tweets or my radio interview made any difference is immaterial. What is important is that within less than 3 weeks of Kyle-Sidell’s first appeal on social media, the management of COVID-19 lung infections has changed radically to incorporate his thinking and that of Professor Gattinoni.
Thus on April 6th 2020, the Chief of Pulmonary and Critical Care Medicine at the Eastern Virginia Medical School in Norfolk Virginia, Dr Paul Marik MD, circulated his hospital’s Critical Care COVID-19 Management Protocol (27). Included in the document are the following statements:
“If what you are doing ain’t working, change what you are doing”.
“We have zero success for patients who were intubated. Our thinking is changing to postpone intubation for as long as possible, to prevent mechanical injury from the ventilator. These patients tolerate hypoxia surprisingly well. Natural course seems to be the best”. Comments of Dr AB from New York City.
“This is not your ‘typical ARDS’. Mechanical ventilation may be doing harm. We need to think of alternative treatment strategies”
On April 21st 2020 a group of intensive care physicians from Bangkok, Oxford, Amsterdam, Hayatabad Peshawar (Pakistan) and Lalitpur (Nepal) (28) proposed that if ventilators were used more sparingly, the high death rates for COVID-19 patients treated with IV could be reduced: “The presence of only hypoxemia should in general not trigger intubation because hypoxemia is often remarkably well tolerated. Patients with fatigue and at risk for exhaustion, because of respiratory distress, will require invasive ventilation. In these patients, lung protective ventilation is essential. Severe pneumonia in COVID-19 differs in some important aspects from other causes of severe pneumonia or acute respiratory distress syndrome, and limiting the positive end- expiratory pressure level on the ventilator may be important. This ventilation strategy might reduce the currently very high case fatality rate of more than 50% in invasively ventilated COVID-19 patients” (26, p.1).
Then on April 24th 2020 the Journal of American Medical Association published new guidelines for the management of COVID-19 respiratory distress (29). The key change was to promote the use of IV only when the physiology suggests this invasive procedure will help.
A number of newspaper reports show the rapidity with which this change in medical practice, a complete reversal of an accepted practice, has occurred in no more than 10 days (30-36). This is utterly unprecedented in the history of medicine. Usually new ideas take between 10-20 years to be accepted and implemented.
Importantly, the paper from New York City (9) reported that close to 90% of patients placed on IV, died (36).
Thus what I said in my radio interview on Wednesday 8th April 2020 that there was increasing evidence that IV was not the ideal treatment for COVID-19 ARDS has proved 100% correct and is completely accepted today, less than three weeks later.
Importantly, at no time in the interview did I demean or disparage medical doctors or scientists. I simply said that the new evidence shows that the method of treating “silent” hypoxia in patients with COVID-19 infections may be causing more harm than good.
Time has proven that my statements on “silent” hypoxia are absolutely correct. And therefore, far from being “dangerously misleading”, my interview may have helped save lives by spreading Kyle-Sidell and Gattinoni’s ideas more widely on Twitter.
It is interesting that the British Prime Minister Boris Johnson was admitted to St Thomas’s Hospital in London on 5th April 2020 with severe respiratory distress due to COVID-19 infection. He subsequently praised the hospital for saving his life. It seems possible that the avoidance of IV may have been a key reason why he survived.
Yet had he fallen ill just a week or two earlier he might have been treated with IV, perhaps with a different outcome.
- The cause of the “silent” hypoxia in severe COVID-19 infections.
Both Kyle-Sidell and Gattinoni have hypothesized that an interference in blood flow distribution within the lungs – so-called ventilation/perfusion deficits – explains why persons with Type L and Type H COVID-19 lung infections have more similar reductions in their blood oxygen contents despite very different degrees of lung involvement (Figure 1).
From the start this seemed an improbable hypothesis to me. Accordingly I wondered if the real cause of the “silent” hypoxia, in addition to the clearly established lung involvement (Figure 1), might be an altered functioning of the red blood cells produced by the COVID-19 virus.
My reading soon uncovered substantial evidence that the function of red blood cells could be affected by the Coronavirus (37). Thus anaemia (36) and elevated blood ferritin concentrations (38,39) are found in at least half of patients hospitalized for COVID-19 infections. The elevated blood ferritin concentrations would likely result from release of stored iron from within red blood cells. Indeed elevated blood ferritin concentrations on hospital admission were found to be a predictor for the development of critical illness in one study (39).
A meta-analysis of all recently reported studies (40) found that blood haemoglobin concentrations were significantly lower in patients with severe COVID-19 infections than in those with milder forms. This provides further evidence that red blood cells may also be a target of the COVID-19 virus.
Using a computer modelling approach Liu and Li (41) proposed that once inside the red blood cells, the COVID-19 virus might be able to attack the haemoglobin molecule releasing iron and the released iron might then have toxic effects on the body. This hypothesis has since been vigorously attacked as being highly improbable (42). Yet as an hypothesis it remains neither proven nor disproven
The reason I broached the hypothesis of red cell involvement in the radio interview was to provide listeners with some background for the discussion of the critically important issue of “silent” hypoxia.
If the hypothesis of impaired red cell function in persons with COVID-19 infections is wrong, it does not detract from my key messages relating to how “silent” hypoxia is best treated.
- The value of hydroxychloroquine in the treatment of COVID-19 infections.
During my interview I briefly mentioned that if the red blood cells are indeed targeted by COVID-19, then the use of the anti-malarial drug, hydroxychloroquine (HCQ), might be helpful. I did not ever advocate that this should be used in treatment.
As is his practice and using the same well-oiled tactics for developing a falsehood as he did with the claim that I am “anti-vax”, Geffen again wilfully distorts what I said.
Now he writes: “Then comes the most dangerous part of the interview. Noakes punts hydroxychloroquine as a treatment for the virus. He says there is good evidence for the drug…. It is highly irresponsible and unethical for Noakes to be promoting its use to the general public”.
Which of course I was not. But that does not fit Geffen’s game plan.
He concludes with his usual character assassination: “It’s also troubling that Noakes demeans the scientific and medical community in a radio interview (and also on Twitter). If he has theories to propose, he should do so in scientific journals or even by writing articles and posting them on one of the arXiv so that other scientists can critique or debunk them”.
I have but two comments. Nowhere in my interview did I “demean” the scientific and medical community. I simply indicated that it was critical to understand the concept of what is now termed “silent” hypoxia and to avoid IV if patients’ lives are to be saved.
Second I am now happy to provide this article to be critiqued and debunked.
But let’s return to the question of HCQ use in COVID-19 infections.
Geffen well knows that the use of HCQ in COVID-19 infections is no longer a matter of science; it has become a political and economic football.
The political angle is that President Trump has publicly proposed that the use of HCQ might be of value in COVID-19 infections. From that moment, anyone supporting the use of HCQ was clearly a Trump supporter and therefore politically unacceptable in the circles in which Geffen moves.
The economic angle is that HCQ costs just $0.80 per tablet as compared to $1000 for the competitive drug, Remdesivir, naturally favoured by the pharmaceutical industry. Unfortunately Remdesivir has so far proved a spectacular disappointment.
There is also the concern that if HCQ were to prove effective, this might detract from an agenda to enforce COVID-19 vaccination on all the world’s population.
The evidence of whether HCQ is effective or not is the focus of a number of clinical trials currently underway as Geffen details. What he fails to mention is that clinicians who claim benefit of HCQ note that it must be given at the onset of symptoms and in combination with zinc and Azithromycin (AZ). Most of the clinical trials reporting HCQ failures have not adhered to those guidelines. In particular they have begun treatment when patients are already critically ill with COVID-19 pneumonia.
The largest clinical trial so far reported is that directed by Professor Didier Raoult of the IHU Mediterranee Infection, Marseille, France. Professor Raoult is rated as the world’s number 1 scientist in Infectious and Communicable Diseases.
In his recent study (43) 1061 patients were treated with the HCQ/AZ combination. Professor Raoult had concluded: “The HCQ-AZ combination, when started immediately after diagnosis, is a safe and efficient treatment for COVID-19, with a mortality rate of 0.5% in elderly patients. It avoids worsening and clears virus persistence and contagiosity in most cases”.
Thus any promotion of the appropriate use of HCQ (in appropriate combination) is not “highly irresponsible and unethical”.
In contrast, it might just be life-saving.
As maybe the advice that most people with COVID-19 pneumonia will be more likely to survive if they do not receive IV.
Oh, and by the way, a recent meta-analysis reports that chronic use of chloroquine or hydroxychloroquine by persons with rheumatic diseases was associated with a reduced risk for the development of cardiovascular disease (44), clearly an unexpected benefit.
If Dr Geffen wishes to be taken seriously in his position as the new Director of the Centre for Science and Technology Mass Communication (CENSCOM) in the Department of Journalism at the University of Stellenbosch, he really needs to learn that playing the man, on fake grounds, is not what credible journalism is all about.
Journalism needs to be about Truth.
Not about character assassinations through the wilful creation and dissemination of malicious falsehoods.
For it is as Einstein warned: “Whoever is careless with the truth in small matters, cannot be trusted with important matters”.
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