A non-blog by Luca Ammendola

EVERYTHING YOU ALWAYS WANTED TO KNOW ABOUT COVID* (*BUT WERE AFRAID TO ASK) – PART ONE

From the film “Everything you always wanted to know about sex* (*but were afraid to ask)”
by Woody Allen

DISCLAIMER: The following article is the result of the work of Mauro Scardovelli (university rector of Unialeph, an Italian university founded with the goal of teaching and implement the values of the Italian Constitution) and his team. All the information you will find was presented by some of the best medical minds Italy has to offer, most of them have been on the frontline of the Covid crisis since it’s beginning. I stand on the shoulders of giants. All I’ve tried to do is to summarise, organise and simplify (wherever possible) the information they provided in an attempt to make it understandable to all. Most statistics are based on the situation in Italy (which is the worst in Europe and therefore a good case study). The following is an exercise in reasoning (from the latin rationem: to understand the causes). This article does NOT constitute an official medical protocol. If you have any symptoms you MUST contact your doctor. The article is divided in two parts. PART 1 is an overview of the medical aspects of the crisis. PART 2 covers the political, social and economic consequences. 

OVERVIEW

Let’s begin with the basics: a new virus has made it’s way into nature; it’ called SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), it belongs to the family of coronaviruses and causes the “Coronavirus disease 2019” (COVID-19). The first case was identified in Wuhan, China in December 2019 (although both the timing and the location are subject of debate). The World Health Organization (WHO) declared the outbreak a pandemic on 11 March 2020.

The origins of this virus are as of today still unclear. It exist three main hypothesis. One: the virus is of animal origin (the famous wet market bat hypothesis) and then mutated to infect humans. Two: it is a man made virus (near Wuhan there is a laboratory that studies viruses, namely bat related viruses) that escaped from researcher’s control. Three: it is a biological weapon released on purpose on the population (we don’t know by whom or why). The three options are very much a possibility but, like I said, we don’t yet know for sure and any conclusion, as of now, would be purely speculative.

Whatever it’s origin the virus EXISTS and is moderately to highly contagious(depending on who you talk to). 

In the overwhelmingly majority of cases the virus provokes no reactions (asymptomatic) or very light reactions (paucisymptomatic) in the infected person. BUT in some cases it provokes a very serious pulmonary hyper-inflammation that can lead to a so called “cytokine storm” (more about this later). In some cases this can lead to death.  

PATHOGENESIS OF THE VIRUS

(Pathogenesis: the mode of production or development of a disease.)

The Covid disease has three development phases.

PHASE 1: Viral response phase

An initial phase, purely virological, in which viral replication prevails. It is usually a phase characterised by a clinical symptomatology that isn’t particularly serious such as fever, bone-aches, headaches, nausea, diarrhea… This viral phase tends to diminish because the host’s inflammatory response is triggered. (For most patients this is useful because it helps control the infection. That’s why fever exists in the first place: it is a natural defence mechanism. High temperatures, over 38 degrees celsius, kill viruses.)

PHASE 2: Pulmonary phase

As the inflammatory response takes hold, the virological response yields. This is what happens in all Infectious diseases. Up to this point (halfway into the second phase) the disease is no worse than the common flu. In most cases (between 80% and 90% of the infected symptomatic patients) it is a mild disease which heals by itself in about ten days and without complications. BUT in a number of patients (the remaining 10%-20%) a dysregulated inflammatory response (an excessive inflammatory response) is triggered, leading to the third phase of the disease.

PHASE 3: Hyper-inflammation phase

In some patients an excessive and dysregulated inflammatory response is triggered. A real “cytokine storm” (Disseminated intravascular coagulation), which leads the patients to a haemophagocytic syndrome (disorder of immunoregulatory abilities), to respiratory failure, to intensive care and in some cases to their death.

GOAL OF THE THERAPIES

If there is one thing all doctors seem to agree on this is the time factor. The fight against the Covid disease is a race against time, the medical intervention must be prompt. Medical intervention must be aimed at the first and second phase of the disease. When patients enter the hyper-inflammation phase it becomes much more difficult to help them. 

So, basically, the antiviral therapy should be concentrated at the beginning of the disease. When we move into the hyper-inflammatory phase of the disease, antiviral drugs are no longer of any use. At that point all therapy is based on the modulation of the excessive inflammatory response, on turning off this “cytokine storm” that generated in the patient’s lungs.

In between these two extremes, of course, there is an intermediate zone which, in the opinion of many doctors, is the zone in which the maximum therapeutic effort should be concentrated.

The goal of the therapies should be to intercept patients in the initial phase of the disease and immediately treat them with antiviral therapy.

If the patient evolves towards the hyper-inflammatory phase, the other goal is to intercept the onset of this excessive inflammatory response early to avoid being faced with patients in whom the containment of the excessive inflammatory response is very difficult. At that point the whole game is played on their resistance to ventilatory therapy. 

So being precocious with the therapy should ideally avoid the evolution towards the third phase of the disease, therefore save lives and reduce hospitals/intensive care admissions.

THERAPIES

Most doctors are confused about treatment because, as of today, no one has provided an official therapeutic plan. The government and health institutions have been suggesting what treatments NOT to use but nobody took the responsibility to advise the use of a specific therapy. 

So doctors on the frontline had to invent/create one using the fruits of the experience and observation they acquired by the bed of the patients; outside the laboratories, outside mental ruminations. And this is what they found:

Drugs play different roles at different times. Different drugs are needed during the three phases of the disease.

PHASE 1: Antiviral therapy should be concentrated at the beginning of the disease. Doctors cannot remain idle and allow people to stay in bed without having a proper therapy or, even worse, with a therapy, for instance Paracetamol, which can be harmful (Paracetamol is dangerous in Covid patients because it creates a depletion of glutathione reserves, which is essential as an antioxidant and is very useful in anti-inflammatory reactions. Removing glutathione means opening the doors to the advancement of the inflammation.) Phase 1 must be addressed with anti-viral and anti-inflammatory remedies that block or reduce the inflammatory state (for instance vitamin C and D). There is one specific drug that has been shown (on the field) to be the most effective at this stage. But we will cover this (extensively) in the next chapter.

PHASE 2: anti-viral remedies must be continued for a while but they begin to lose effectiveness. Low-molecular-weight-heparin (an anticoagulant with a strong immunomodulatory activity) must be started as soon as the first signs of hyper-inflammation appear, together with antibiotics. The use of antibiotics is needed because it has an action on possible bacterial super-infections. Why? because an inflamed lung is predisposed to the colonisation of pathogenic bacteria. An inflamed, mucus producing, lung is a fantastic breeding ground for pathogens. We cannot stress enough that timing is essential. The dead patients in March and April were, in most cases, patients on which no intervention was made. They were patients left home alone.

PHASE 3: As we’ve already mentioned patients that reach phase three of the disease are strongly compromised. The medical goal here is to “turn off” the hyper inflammation. This is done with anti-inflammatory and anticoagulant remedies. But these take time to have effect and many patients that reach phase 3 are unable to breath normally. Therefore they most be intubated. Oral-tracheal intubation is a medical practice that can only be done by an intensive care doctor. It is an invasive medical procedure, extremely delicate, that no doctor uses with a light heart; it is literally the last thing they want to (and can) do. It is worth noting that intensive care is seen by most doctors as the failure of the therapeutic strategy and NOT, like it is promoted by governments and in the media, an intelligent and structural answer to the disease. In light of that, having more intensive care as the main response of the system to a viral infection is profoundly worrying.

HYDROXYCHLOROQUINE

As I mentioned earlier there is one specific drug that has been shown (on the field) to be the most effective as an antiviral during the first phase and the first half of the second phase of the disease. This drug is called Hydroxychloroquine and it is one of the most controversial drugs in the Covid affair (some call it the smoking gun, the irrefutable proof of the mismanagement of the crisis).

Hydroxychloroquine is a derivate of Chloroquine. It is drug that has been in use for a long time, the American FPA approved it in 1955 and it is the 128th most prescribed drug in the United States. It is a particularly tested drug, has a very low cost (a few euros per box) and is easy to supply (it’s a common medicine). It is most commonly used to prevent Malaria and anyone who has travelled in malaria risk areas has taken it (I know for certain I have, multiple times in my life).

The drug can have adverse/side effects (of course it does, all drugs do, even aspirin) but these are negligible. The most common adverse effects are nausea, stomach cramps, and diarrhea. Other common adverse effects include itching and headache. The most serious possible side effects affect the eye, with dose-related retinopathy (damage to the retina). 

Before prescribing the drug the doctor must always ask the patient a few questions (this is the case with ANY drug). The patient must not be affected, for example, by Long QT syndrome (a heart disease) or so-called Favism (an inborn error of metabolism that predisposes to red blood cell breakdown) or other conditions that interact with Hydroxychloroquine. But this it is the ABC of medicine.

The AIFA (the Italian Drug Association – a public authority) initially gave the green light to the use of Hydroxychloroquine but then withdrew it from the market. This was supported by a series of studies conducted in the USA claiming that it can lead to very harmful side effects. But these studies are highly problematic (so much so that The Lancet, the oldest scientific publication in the world, had to retract the one they recklessly and hastily published). Many doctors have no problems calling these studies bogus studies. This because these studies were made on hospitalised patients (patients that had reached the second half of phase two or even phase three of the disease) and with very very high dosages (overdose). In this case it is obvious patients will show harmful side effects. As we’ve seen earlier Hydroxychloroquine is most useful in the early stage of the disease and should be used with the correct dosage. It is worth pointing out the obvious: any drug, if used in very high dosage, can be harmful.

Worse yet (in the writer’s opinion) clinical evidence of thousands of people healed with Hydroxychloroquine has been ignored and/or obstructed by AIFA and the WHO.

Hydroxychloroquine has been used on thousands of patients in Italy at a reasonable dosage and for a reasonable period. The clinical observation of many, authoritative and above all experienced doctors, led to say that in their clinical experience Hydroxychloroquine has been able to positively change the progress of the disease in patients.

Honest doctors talk about the centrality of timing (we’ve covered this many times now). The drug is useful at the onset of the disease. And must not exceed the dosage of 800 mg per day for a maximum of 7 days.

Andrea Mangiagalli, just to give a practical example, one of the first family doctors to test “on the ground” the effectiveness of Hydroxychloroquine, treated 300 patients. He never saw any complications apart from a few patients who had a modest diarrhea (very modest grade 1 or 2). Out of these 300 patients 3 were hospitalised, 1 died and 297 were CURED (I don’t know about you but I’d take those odds any day of the week).

The evidence provided by doctors on the frontline of the crisis has not been small, it is strong positive evidence of the utility of Hydroxychloroquine in the fight against COVID. The kindest thing I can say about the failure to use Hydroxychloroquine is that it’s danger was overestimated by the authorities. Nevertheless it is the writer’s opinion that the failure (because of incompetence or connivance) to use a cure that could have potentially saved thousands and thousands of people is a crime against humanity and must be judged in a court of law.

(UPDATE: on December 11, 2020, after an arduous seven-month legal battle carried out by a group of general practitioners, the Italian Council of State approved the use of hydroxychloroquine as a therapy for Covid-19. The ordinance reads: “The continuing uncertainty about the therapeutic efficacy of hydroxychloroquine, admitted by the AIFA itself to justify the further evaluation in randomised clinical trials, is not sufficient legal reason to justify the unreasonable suspension of its use on the National territory”. Better late than never!)

LETHALITY, MORTALITY AND OTHER STATISTICS

The Italian population is approximately 60,360,000.

At the time of writing (December 5, 2020) according to the Ministry of Health, the total number of PCR tests carried out is equal to 22,767,130 that is 37.7% of the population.

The PCR test positives for Covid-19 are 754,169 or 1.24% of all Italians.

94% of the infected are asymptomatic (no symptoms) or paucisymptomatic (light symptoms).

Patients hospitalised with symptoms are 31,200 that is 4.1% of those tested positive or 0.05% of all Italians.

Of those hospitalised, 3,567 people are in intensive care, that is 11.4% of the hospitalised, or 0.47% of all positives, or 0.05% of all Italians.

The total deaths from/with (hard to say) Covid-19 are 60,078.

The virus therefore has a lethality rate (number of deaths divided by the total of positive PCR tests) of 7.9% and a mortality rate (number of people who died due to the disease divided by the total population) of 0.09% .

The lethality rate of the virus is difficult to interpret due to various problems with PCR testing (which we will cover in the next chapter).

But we can safely say that Covid-19 is a fatal disease but its mortality rate is, percentage-wise, very low. So it is a disease to be taken seriously but not to panic about.

Let’s be clear: Covid-19 is not the “Black death” nor the “Spanish flu” (that in 1918-20, in a time we had no penicillin, Hydroxychloroquine, heparin, antibiotics, cortisone or intensive care, killed between 50 and 100 million people in the space of two years). Covid’s lethality is also much much lower than two modern coronaviruses: Sars-Cov1 (10% lethality during the 2002-04 outbreak) or Mers (37% lethality during the 2002 outbreak). And is incomparable to the lethality of extremely dangerous viruses such as the Avian flu (60% lethality) or Ebola (65% lethality).

To put things further in perspective Covid has a lower annual lethality than road accidents, suicides and respiratory diseases (due to nano-dust/pollution).

It is also worth noting that today (fall 2020) only 0.5% of all positive cases end up in intensive care (this is 30 times less than in March).

The latest survival rate estimates from the Center for Disease Control (CDC-National public health institute in the United States) are:

  • Age 0-19 … 99.997%
  • Age 20-49 … 99.98%
  • Age 50-69 … 99.5%
  • Age 70+ … 94.6%

Finally please consider that 90% of the dead were over the age of eighty and/or had other preexisting diseases (respiratory, cardio vascular, metabolic diseases and/or obesity, diabetes… in short, everything that produces inflammation in our body). This is why healthy children and young people do not get sick or show very very mild symptoms: they have little to no preexisting inflammations in their bodies.

To conclude Covid is a serious disease but we will not all die from it (unlike most propaganda wants you to believe).With this in mind all further reasoning must impose a “risk and benefit” analysis.

PCR TESTING

The most common test (there are others) to test the positivity for Covid-19 is the Polymerase chain reaction test (PCR). It is a method used to rapidly make millions to billions of copies of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it to a large enough amount to study in detail.

To begin I believe it is important to clarify what “being positive to PCR testing” means. Being positive means that the person has, in his body, some nucleic acid (DNA and RNA) of the virus. BUT a positive subject does not mean that the subject is sick. Nor does it necessarily mean that the subject is contagious.

This is because the nucleic acid found does not necessarily represent an infecting viral particle, it can be a residue, a dead virus. Furthermore the nucleic acid found does not necessarily represents a concentration of virus sufficient to infect (yourself and others).

In vitro studies have shown that for infection to occur there must be at least one million equivalent genomes in a clinical sample (the viral load). In other words it is the viral load (and not the presence of nucleic acid) that determines if you’re sick and how sick. BUT the PCR test is unable to measure viral load correctly. This is one of the core problems with PCR testing. 

The second problem has to do with the cycles of amplification and it’s a problem of misusage. In PCR testing the DNA sequences taken from the subject being tested are exponentially amplified in a series of cycles. Imagine (to simplify) a zoom lens: the more you amplify the zoom the closer and more detailed you see. Still simplifying, each degree of zoom amplification is equivalent to one amplification cycle. Now the problem is that when the test is run at 35 cycles or higher it is useless and misleading. I quote Anthony Fauci: “If you get a cycle threshold of 35 or more…the chances of it being replication-competent are minuscule…you almost never can culture virus from a 37 threshold cycle…even 36…it’s just dead nucleoids, period.” This is a generous estimation by the way. The more conservative scientists suggest a maximum of 20 to 30 cycles.

In other words, too many cycles and the test will turn up all sorts of irrelevant material that will be wrongly interpreted as relevant. That’s called a false positive. A PCR test that was run over 35 cycles of amplification will give anything between 50% and 91% of false positives (from the most optimistic to the most pessimistic possibility). 

On 11 November 2020, the Lisbon Court of Appeal in Portugal declared the quarantine of four Portuguese citizens illegal. They gave this reason: “Based on the scientific evidence currently available, this test [the RT-PCR test] is not in itself capable of establishing beyond doubt whether positivity is actually equivalent to infection with the SARS CoV-2 virus. And this for several reasons, two of which are of primary importance: the reliability of the test depends on the number of cycles used; the reliability of the test depends on the viral load present “

The problem of the cycles amplification also explains with we see disparate difference in numbers of contagions between different countries. Germany and Austria, for example, use 25 cycles of amplifications (and therefore have the lowest numbers of contagions in Europe) Italy and France use anything between 35 and 45 cycles (the exact number is difficult to say because the authorities are not clear on this).

I close this chapter leaving the floor to Kary Mullis, the inventor of the PCR test, for which he won the Nobel prize in 1993: “With PCR anyone can be tested positive for just about anything, if you do it long enough (enough cycles of amplification). For this reason, we must be very careful to use PCR as a diagnostic test”.

FACE MASKS

The topic of face masks is a minefield. This is because first, for many people, the masks have become a symbol, a totem of a semi-religious nature. Secondly, and this is more important, because the use of masks produces benefits in certain circumstances but serious damages in others.

The perception most people commonly have is that masks are something uncomfortable, a nuisance, but they must be worn because they are good for your health (since they protect from the virus). This is not correct: masks are a compromise. It is therefore a question of always calculating costs and benefits.

Prolonged use of the mask leads to a worsening of cardio-pulmonary performance and a reduction in respiratory function. This is harmless in healthy subjects who wear the mask for short periods but dangerous in subject with heart diseases. This is because the heart must make up for the fact that the lungs don’t work as well as they should. So the heart is under considerable stress while a subject wears a mask

Also the few studies available have shown that wearing a mask for prolonged period of time leads to worsening in respiratory virosis (respiratory diseases caused by a virus), which is exactly what should be reduced or avoided. In other words subjects wearing masks show more symptoms of respiratory infections. 

We must understand what happens in a person’s lungs when you wear the mask: the Italian Ministry of Health says that 95% of what a potentially infectious subject emits is shielded. So the crucial question is: where does that shielded 95% of emissions go? Well, it simply stays inside the mask, moistening it and creating a favourable environment for the development of germs, but above all it is partially re-inhaled. This creates the risk that a person wearing a mask for a long time, which screens and prevents a free exhalation, does amplification cycles of the virus all by himself. By continuing to re-inhale his own viruses, he can push them deep into the lungs and alveoli where viruses shouldn’t reach. In the upper respiratory tract there are the innate adaptive defences that “kill” most of the germs with which we enter into contact while breathing. But in the pulmonary alveoli, deep down in the lungs, these defences are lacking, precisely because the germs should not make their way there. If too many viruses arrive in the pulmonary alveoli and multiply without resistance, when the the antibodies finally arrive, after 10-14 days, instead of finding a little amount of virus, they find huge quantities. A formidable battle follows which creates a very high inflammation. This is exactly what is seen in many cases of subjects who, after a mild onset, after 10-14 days, have an inflammatory explosion and an aggravation.

We should therefore avoid worsening the situation of an asymptomatic by imposing a barrier to exhalation. Because the risk is to turn the subject into a symptomatic, or a paucisymptomatic, by continuing to breathe-in his viruses for a long time.

Wearing a mask is a compromise. Therefore, its use must be modulated and not imposed in circumstances in which it is more harmful than beneficial.

Of course in some cases wearing a mask is a very good idea (for as short a period of time as possible): inside hospitals, in environments with a high concentration of potentially infectious subjects, near COVID patients, in crowds, in public transport…

But outdoors, except in very special circumstances, wearing a mask is totally unreasonable. You cannot receive a sufficient viral load to get infected just walking by a person. The WHO says that you have to stay at close range of an infected person for at least 15 minutes (this even outdoors) to receive enough viral load to get infected. Occasional contact is of no particular importance, it constitutes a potential risk that is absolutely irrelevant compared to the risks of life. So outdoors, except in special circumstances (crowding etc.) masks are of no use at all. The only thing they can do is possibly harm people who have respiratory and heart problems and so on. The former Director of Microbiology in Bern said: “It would be wiser to wear a helmet because something is more likely to fall on your head than getting infected by walking around without a mask”. 

Wearing a mask is a compromise and like all compromises, it is right to push to the point where the harms are outweighed by the benefits and stop when the risks overcome the benefits.

PREVENTION

Almost no one talks about prevention and this is very dangerous because one of the absolutely incontrovertible facts of the COVID affair is that so-called “healthy” patients generally do not get sick and if they do they have no complications. Healthy patients fight COVID with their immune system without much need of therapy. And this is a huge difference. Therefore one of the main goals should be to promote healthy life styles that naturally reduce inflammation inside our bodies. These are basic things like eating healthy, not smoking, drink little to no alcohol, eat little red meat, loose weight if overweight, do regular physical activity and so on. Vitamin C, D and B12 have also shown to be very useful in preventing COVID. In short, anything that can be done to reduce inflammation in the body and increase the effectiveness of the immune system should be done!

Another fundamental aspect that is rarely touched upon is that this disease must be fought on the territory and not in the hospital. It must be fought with and by local family doctors who get to the patients early and begin to apply therapies early. Local medicine must be implemented.

Because very often patients who get to the hospital they do so after having wasted time and show up in complicated conditions. Furthermore the hospitals are places where the disease spreads even more, it becomes a nosocomial infection (an infection that is acquired in a hospital). This makes doctors and nurses sick, reduces their numbers and their work becomes unmanageable.

The sick must be treated early and at home, freeing hospital beds to patients with much more serious diseases such as cardiovascular diseases, tumors, etc.

MEDIUM/LONG MEDICAL CONSEQUENCES OF THE CRISIS

Hospitals today have stopped most activity that is not COVID related. Most screenings, check-ups, medical visits and so on have been reduced or postponed. This means thousands and thousands of people who didn’t have their heart checked, that didn’t screen for cancer and/or other pathologies. The prevention of highly lethal pathologies is in stand by and this is very very dangerous.

Furthermore sick people don’t go into surgery. This is obviously a huge problem. Imagine a patient with an operable cancer. If 15-20 days pass without surgery, nothing happens, but if 3-4 months pass, the problems are accentuated and this can lead to some very very serious problems down the line. Because the tumor will not stand still; it will progress (and likely become inoperable). The same can be said for patients with acute myocardial infarction, or cerebral stroke and so on and so on. All these other pathologies still exist and need to be treated. In the coming months thousands of people will die from lack of treatment

It is also worth considering that the Italian National Institute of Health (Istituto Superiore di Sanità) signed a report on motor activity in 2018 in Italy based on which during that year there were an estimate 88,200 deaths due to the fact that not enough physical activity was done in the average population. A little less than double the deaths that are today attributed to Covid19 (which are 36,000 and some). If we think about the limitation of motor activity that occurred with the lockdown, it is likely that the situation in 2020, in regard to deaths from insufficient physical activity, will increase.

Finally the consequences of the extreme measures taken by the authorities (lockdowns, freezing the economy…) will have profound consequences on the “social health” of the population. We’ve already seen spikes in the numbers of deaths by suicide, overdose and so on

If the economic crisis continues we will see more and more of these problems and things like malnutrition and possibly starvation will become serious health risks. 

END OF PART 1

In part 2 of this article we will cover the social, economical and political aspects of the COVID-19 crisis. 

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