metaanalysis on COVID-19 pathomechanisms

COVID-19 meta-analysis

Study on the state of knowledge on the pathomechanism of COVID-19, as of mid-April 2020
Author: Peter Dirscherl, co-authors: Heide Ritter, Steffi Wolff
Structure:
Question
Introduction: author, motivation and method
Main features of SARSCoV2
The pathomechanism(s) of COVID-19
Conclusion
Question:
How exactly does the SARSCoV2 virus damage the human body when it triggers the
disease COVID-19?
Lead author, motivation and methodology:
The author Peter Dirscherl is a doctor.
The in-depth study of scientific sources and at the same time intensive observation and
discussion of all publications available to him in the media and on various social media
channels on the subject of “new coronavirus” with a scientific background enable the author
to take a well-founded position.
The aim of the study is to optimize the way the coronavirus pandemic is dealt with in order to
ultimately be able to contribute as far as possible to preventing further infection of the
population. It is very important to be familiar with the first reports and experiences, especially
from China, although these sources have unfortunately often been retracted from being
publicly available in the meantime.
The method is descriptive and there is no meticulous citation of sources, because the time
required for this appears disproportionately high under the existing time pressure, with a
dynamically spreading epidemic, and because recipients should be well able to do research
in the age of the Internet to put up postulates and to review sources for the research results
mentioned.
Main characteristics of SARSCoV2:
Like all corona viruses, the SARSCoV2 virus is a zoonotic pathogen that can reproduce in
humans as well as in various mammals and birds. Mutual infection is possible through the
virus reservoirs in different animal species.
The virus has an extremely high affinity for human ACE2 receptors on cell surfaces and,
after binding to the angiotensin converting enzyme II, reaches the human body cells via
these receptors, where it can multiply. Due to the high binding affinity, a very small amount
of virus compared to other human pathogenic viruses is sufficient to trigger an infection.
SARSCoV2 is sensitive to alcohol and heat and becomes harmless when heated for several
minutes from 70 degrees Celsius. Recent research results that contradict these early
findings by Taiwanese scientists appear to be poorly validated. At normal room temperature,
the virus can persist infectiously on surfaces for up to several hours. Previous studies have
shown that similar coronaviruses can remain infectious in dried saliva for several weeks.
The virus genome is similar to the corona virus genome known in bats and pangolines.
A group of Indian scientists led by Prashant Pradhan published a study as a preprint on
January 30, 2020, which concluded that more than 10% of the genetic sequences of
SARSCoV2 have no similarities to known coronaviruses, but instead have similarities to
sequences of the HIV virus, what prompted these researchers to postulate the thesis that it
was a synthetically designed bio-weapon.
This study was initially withdrawn for unknown reasons. In recent weeks, however, signs of
the plausibility of the thesis of the Indian researchers have increased.
The pathomechanism(s) of COVID-19:
The virus enters the human body almost exclusively via mucous membranes, but it is
theoretically also a sanguine transmission pathway through blood products / products and
contaminated needles in i.v. Drug use possible. SARSCoV2 gets into the human body cells
through the mouth, throat, nose, and above all also the mucous membranes of the eyes,
more rarely also through the anal and genital mucous membranes. The amount of virus
initially taken in seems to play an important role in pathogenicity. SARSCoV2 is most
commonly transmitted by droplet infection of particles exhaled when speaking or coughing /
sneezing. The virus also occurs in smaller particles than aerosol in the air, but then there
must be a highly infectious person in the area to allow infection. This transmission path is
particularly relevant in hospitals, supermarkets and in public transport, which is why it can be
advantageous to wear protective goggles in these places as well as closed protective
glasses to protect yourself from infection. Lubricating infections with a fecal-oral transmission
path and via the hands also represent a not to be neglected risk of infection. SARSCoV2 is
often excreted by stool in infected people and can theoretically also spread via wastewater
disposal channels, e.g. about animals or aerosol emissions. Infection through sexual contact
with infected people does not appear to be excluded either.
After infection, if the amount of virus is too large to be immediately made harmless by the
immune system and there is an increasing virus multiplication by replication in the affected
body cells, the first symptoms of COVID-19 usually appear after a few days.
The disease usually begins with an initial respiratory phase with runny nose, sore throat,
difficulty swallowing and coughing. Headaches, loss of smell and flu-like muscle and body
aches combined with an intense feeling of exhaustion are also common early symptoms.
Sometimes digestive complaints with nausea and diarrhea occur. The gastrointestinal route
of infection does not seem to play an important role for the initial pathomechanism. It can be
assumed that the viruses are mostly made harmless by gastric acid during gastric passage.
The pronounced exhaustion is probably related to an incipient systemic immune response.
When this intensifies, fever often occurs. If additional breathing difficulties with shortness of
breath occur, this usually signals the transition from the first local respiratory illness phase to
the second, very dangerous, systemic illness phase.
The dreaded and often fatal “Wuhan pneumonia” is the central complication of an infection
with SARSCoV2. If the typical glass bottom-like finding of this pneumonia is visible in chest
CT, there is usually also a viremia and the virus gets into blood cells. In particular, the
number of leukocytes drops sharply, which contributes to a typical dysfunctional response of
the immune system and, with increased local interleukin release in the affected organs, i.e.
initially mostly in the lungs, also contributes to significant edema formation. It is not
uncommon for cytokine storms and very high fevers to occur as part of the enormous
immune balance. The faster a systemic spread of the virus occurs with a severe course of
the disease, the less the immune system is able to build up a targeted immune response
using IgG antibodies. This is particularly unsuccessful because CD-4 lymphocytes in
particular are affected and can no longer fulfill their function as memory cells.
In the systemic phase of COVID-19, when adult patients usually become ventilators,
progressive multi-organ failure quickly occurs, which process is exacerbated by the existing
lack of oxygen and by the decay of blood cells and electrolyte shifts. Lack of oxygen and
hypokalaemia alone can lead to organ damage. In addition to the reduced oxygen
absorption capacity in pulmonary edema and reduced cardiac ejection, the lack of oxygen is
also essentially caused by the virus’s binding to hemoglobin and the associated functional
impairment. The role of associated changes in iron metabolism are still controversial.
The development of pulmonary fibrosis is a serious and frequent complication of patients
with severe disease courses, but has also been reported as a late complication in milder
courses.
Kidney function is impaired by the deposition of cell decay products and immune complexes,
as well as by electrolyte shifts and by direct viral organ involvement, and kidney failure
requiring dialysis often occurs.
Heart attack causes cardiomyopathy and pericardial effusion. In addition, hypokalaemia
affects the conduction system, which can lead to sudden cardiac arrest.
Inflammation also affects liver function considerably, which can also impair the function of
the coagulation system and lead to bleeding or embolism and infarction.
It is known from post-mortem reports that fibrotic changes in the testicular tissue often occur
when COVID-19 is severe. Similarly, it can be assumed that the ovaries will also be affected.
Veterinary studies have shown that the presence of viruses in the cerebrospinal fluid is
correlated with the viral load in the blood of coronaviruses. The viruses are most likely to
enter the nervous system in immune cells. Neurological and neuropsychiatric symptoms are
not uncommon complications with COVID-19. Epileptic seizures, cognitive impairments and
affect control problems can occur. The latter may be explained by a virus uptake into the
nervous system via the olfactory bulb in the respiratory phase of the disease. As with any
infectious sepsis, dementia as a late complication is a common complication. In principle, the
SARSCoV2 virus should also be able to replicate in nerve cells, but there is as yet no
reliable scientific knowledge about the extent and the possibility of rapid virus multiplication
in nerve cells. Neurologic symptoms may also relate to endothelial inflammation.
There are findings that SARSCoV2 has bacteriophage properties and leads different
bacteria that are commonly prevalent in the mouth, nose and throat to be more harmful.
That could eventually explain why antibiotics are so essential in treatment of Covid19, as Dr
Zelenko proved with Azithromycin.
Unfortunately, effective immunity rarely develops, particularly in the case of severe courses,
so that in the event of a severe first systemic episode of COVID-19 that has been overcome,
it must be expected that renewed infection from outside is possible.
Since the SARSCoV2 virus is taken up in erythrocytes, where it cannot replicate due to a
lack of cell nucleus, a virus reservoir in the erythrocytes persists even after systemic disease
phases have subsided, which can occasionally trigger auto-re-infections in the sense of
relapse fever. There have also been reports of medication-mitigated disease-free pneumonia
that also have malaria-like relapsing symptoms that are most likely to be mild viremia.
Erythrocytes have an average survival time of approx. 100 days and are degraded by
immune cells, especially in the spleen, which, with sufficient viral load, leads to renewed
viremia, without a simultaneous antiviral medication, due to a high percentage of
virus-infected erythrocytes with a weak immune response systemic episode of disease.
Because the progression of COVID-19 disease with systemic episodes is difficult to treat and
has a poor prognosis, early drug treatment appears to be absolutely necessary in all cases
that are not associated with very mild symptoms. It is not necessarily a question of complete
virus eradication, since any relative reduction in virus replication also helps to reduce the
course of the disease and thus reduce the risk of death and the development of late
complications.
In children, severe courses with multi-organ failure and fatal outcome are less common.
Since the child’s immune system is not yet fully developed, SARSCoV2 is usually not as
targeted in children as in adults
trigger immune-regulatory processes described above, which are of central importance for
pathogenicity.
The pathogenicity is also gender-dependent, which can best be explained by the role of sex
hormones in RAS with the influence of aldosterone. The RAS is more reactive under the
influence of male sex hormones and so the SARSCoV2 viruses can find more docking sites,
which can contribute to an average faster virus multiplication after infection in men.
The public is currently often postulating that there are no effective drugs against COVID-19
and one has to wait until a vaccine is available. The opposite is the case: there are definitely
some known effective substances and medication strategies that can have a significantly
positive impact on the course of the disease or even prevent infection or triggering the
disease in the event of infection, even if these scientific mechanisms of action described with
good evidence are still due to the time pressure could not go through the regulatory approval
process.
On the other hand, there is little hope for the development of a well-effective vaccine,
because even after the appearance of SARS 17 years ago, despite intensive efforts, it has
not been possible to develop effective vaccines against coronaviruses for humans. The
ubiquitous coronaviruses, which lead to common colds, also do not have the property of
causing longer-lasting immunity in humans, which is why these infections can be acquired
again and again. Developing immunity through cross-reactions is just as unlikely as building
up herd immunity, which, just like the hope of a vaccine, will remain pious wishful thinking
without sufficient scientifically based evidence. The pathomechanism of COVID-19
described above with the targeted immunodysregulatory effect due to the preferred
involvement of lymphocytes, analogous to the pathomechanism in AIDS, usually prevents a
normal immune response, as is known from other viral infections. It would be most
conceivable that a limited effectiveness of a vaccine could have a certain chance of success
through the replication of thermolabile SARSCoV2 viruses, analogous to the veterinary
procedure in the feline coronavirus epidemic FIP.
One must therefore assume that it will only be possible to get the epidemic under control
through consistent virus isolation and drug strategies, possibly also as prophylaxis. The
alternative of allowing a “controlled epidemic” of the population appears to be undesirable for
all people due to the devastating effects described above, with a significant reduction in the
average life expectancy by several years and a massive disruption to the general quality of
life due to permanently necessary tightened hygiene measures and the associated
restrictions on fundamental rights.
Conclusion
SARSCoV2 is a zoonotic virus that carries properties of typical coronaviruses and of
HIV. Furthermore it seems to be a bacteriophage that reacts symbiotic with bacteria
that live in the mouth, nose and throat and makes them more harmful.
There seem to be more than only one pathomechanism. The different
pathomechanisms and their interactions make it very difficult to understand how
exactly Covid19 deteriorates the health of infected persons and why it’s
pathogenecty is so different in each affected human.
The immunodysregulatory effect of the pathogen means that it is very difficult for the
human body to build up a normal immune response and one cannot count on the
development of individual immunity or herd immunity. The development of a
well-effective vaccine is not very promising.
The course of the disease of COVID-19 can be differentiated into two phases: a
respiratory phase, which can pass into a second systemic phase if there is a high
initial viral load and/or a weakened immune system.
Depending on its severity, Covid-19 triggers pronounced fibrosing organ changes
with serious loss of function.
Because of the great individual and social damage, the population should be
prevented from being infected.
The systemic phase of the disease with viremia often shows a foudroyant course
with multiple organ involvement and there is a possibility that auto-reinfections occur.
Therefore COVID-19 can be described as relapsing fever. The erythrocytes play an
important role as the most likely retreat for SARSCoV2-viruses in the body.
Well-effective drug treatment methods are available with sufficient first evidence,
which should be prescribed on an outpatient basis in the early stage of the disease,
ideally contactlessly with telemedicine. This requires a easily accessible test
infrastructure. Limitations on outpatient prescription options are counterproductive.