English

Understanding Covid-19

By Sunday October 4th, 2020October 15th, 2020No Comments

 

The coronavirus is here to stay with us as its eradication is impossible. Therefore, it is important to prepare for a second wave or for an eventual infection. The coronavirus is a virus of middle danger. An infection might be very light or not be felt at all. However, under certain circumstances an infection might become very serious and lethal. It is therefore important to improve the circumstances.

The official approach to the Covid pandemic has been the approach of avoidance. But the usually propagated measures (wash your hands, keep distance, wear a mask) are simply not enough. Moreover, people become tired of them.[1] The usual appeals “be responsible!”, “take care!”, etc., strengthen the extrinsic motivation, as it is called. But the extrinsic motivation has the tendency to decline soon. We know this with our intentions to lose weight or to exercise more. Extrinsic motivation mostly does not provide the necessary energy to change our behavior. Moreover, the usual coronavirus instructions give us no means to take part in any active process. They leave us in a passive state and they ultimately infantilize people.[2]  All this does not lead to a sustainable and responsible behavior. More effective is to strengthen the intrinsic motivation. Intrinsic motivation is based on a positive experience. One must feel good and alive. Intrinsic motivation needs choices and the ability to participate in certain activities. The best way to face the Covid pandemic would be to improve our immune system, our health and our psychosomatic well-being. But just to follow certain advices and recipes is not enough. To understand what is happening with us would be a major step towards an intrinsic motivation.

The complexity of medicine

“The coronavirus acts like no pathogen humanity has ever seen.” This is the conclusion of the most influential scientific magazine SCIENCE.[3] Indeed, the disease Covid 19 has many different faces. Besides the disease of the lung, it might lead to an inflammation of the vessels, the heart, the brain, to acute kidney injury[4] and even necroses of the intestine are seen.[5] It is a multiorgan-virus.[6] However, others believe that also the flu, a disease Covid 19 is regularly compared with, would have as many faces, if we would look at it with the same care. [7]

In fact, all middle to severe infections create different clinical pictures in the infected person and might have a wide range of short-and long-term impacts. We only must observe carefully. Syphilis is probably the most versatile. However, Covid 19 is such a star among the diseases that even a rare symptomatology might become an international topic. Covid 19 makes many people for the first time aware of a major characteristic of medicine: its complexity.

No other science is as complex as medicine.[8] It is so complex that many do not consider medicine as a science at all. Physicians, since the time of Hippocrates, are more often regarded as artists. Richard Smith, the former editor of the British Medical Journal, one of the leading medical journals of the world, compared physicians even with Jazz musicians.[9] Smith later became very critical about the officially published medicine, doubting their scientific value. For him medical journals have lost their creditability and have become an extension of the marketing arm of pharmaceutical companies.[10]

This is an important topic as medical journals play a crucial role in how scientific medicine is seen. They are – to a big share – responsible that medicine has become a profession with the main task to give drugs or to vaccinate. This restriction becomes painfully sensible during the Covid pandemic as drugs hardly work and a vaccination is not in reach.  Moreover, both, vaccines and drugs had no major contribution to the improvement of the public health of the last 150 years. The so-called curative medical measures played only a little role in the mortality decline.[11]

 

The Hygiene Movement

The main change in the public health came with what is called hygiene. Washing hands and body, safe drinking water, sewerage and good hospital care were the best ways to treat infectious disease in former times. This was complemented with quarantine and social distancing during epidemics.

In the year 1885 the English city of Leicester decided to abandon vaccination against the smallpox, because of the serious side effects. The ill were isolated and provided a special, intensive hospital care. With these measures they had better results and a better public health than comparable cities that just vaccinated without such minute measures of hygiene.[12]

Yet hygiene was always much more than that. It included the improvement of the individual robustness and health. Body exercise, clothing, nutrition and child upbringing were an essential part of the hygiene movement. The terms sleep-hygiene, psychosomatic hygiene, or even psychosocial hygiene are common expression demonstrating the wide range of topics hygiene is concerned with.

From the end of the 19th century, the hygiene movement was mainly in the hands of lay organizations. Especially the socialist movement tried to improve the health of the workers with the whole range of hygiene measures. Germany was the country where the principles of hygiene led to a movement called reform of life (Lebensreform) that had a major impact on social life. The best-known society (Kneipp-Verein) dated back to the German priest Sebastian Kneipp (1821-1897) with a major impact on society, from leisure hours, to working time to school activities. His society had been still very active until the 1960. When I was young, I took part in many of these activities to improve the robustness. It was a natural part of our life then. We who did this in our youth belong today to the susceptible group for Covid-19. May be the low mortality of Covid in German is also a result of these early health trainings that shaped in one way or another our health and our health behavior. This would make much more sense than postulating an immunological dark matter for Germany,[13] to explain why Germany did quite well during this pandemic.

 

Germ theory and hygiene hypothesis

Hygiene as a medical science dates to the End of the 19th century and the Bavarian Max von Pettenkofer (1818-1901) is regarded its father. Von Pettenkofer had a bizarre dispute with the father of infectiology, Robert Koch (1843–1910). Koch was the first to investigate microorganisms as the cause of diseases (Koch’s postulate). For example, he discovered the germ of tuberculosis (Mycobacterium tuberculosis) and described its role in the disease. This dispute is not only of historical interest. It demonstrates a fundamental tension between the view of infectiology (a disease is caused by a microorganism) and the view of the hygienists (living organisms have the means cope with diseases).

For von Pettenkofer a disease was not caused by a microorganism but was the result of bad hygiene. To prove that Koch is wrong, he and his pupils drank water contaminated with Cholera bacteria. As they had no or only slight symptoms, they felt confirmed. [14]

Although the hygiene provided more to the public health, for example in the reduction of tuberculosis, Koch’s postulate became the norm and the principles of hygiene were forgotten. We observe this during this Coronavirus pandemic where virologists and infectiologists are the stars and official advice for the improvement of health are rare.

But under the surface this old discussion lingers on and became more prominent during the last 20 years where chronic diseases became the major problem in the medical world. They also play an important role during this coronavirus pandemic, as people with a chronic disease are more prone for a severe course of Covid.

The so-called germ theory postulates that many if not all chronic diseases are caused by infectious agents (microbes).[15] Diseases attributed to infections are diabetes, asthma, cancer, rheumatic diseases, multiple sclerosis, chronic fatigue, depression, obesity, and even psychiatric diseases.[16] That is, an infection sets forth an immunological process that leads to severe diseases. That there are attempts to treat even depression with antibiotics[17] makes absolutely sense in the frame of the germ-theory.

On the other side is the hygiene hypothesis. It postulates that the reduced contact with infectious agents leads e.g., to allergic disease and that the contact with a lot of microbes is helpful for the function of the immune system,[18] thus contributing to a better health. The extensive research on our microbiological flora, the so-called microbiome, during the last decade shows the importance of having contact with a wide range of bacteria. We have trillions of microbes in and on us. The right composition of this flora is important for our health. This has been established in chronic bowel diseases like colitis or Morbus Crohn,[19] in vaginal infections or in infections of the skin.[20] Some bacteria help to fight off infections.[21] The healthy microbiome also influences our behavior,[22] our mood[23] and might prevent dementia.[24] Diseases like multiple sclerosis might start with a spoiled gut flora.[25]

The study of the microbiome explained also why Pettenkofer and his pupils did not get ill from ingesting Cholera bacteria. According to the microbiome the susceptibility to Cholera changes.[26] As our microbiome depends on nutrition, exercise, stress management[27] and many other life-style factors, we might say that Pettenkofer was right, or at least not wrong.

The course of Covid 19

The typical symptoms for Covid are those of a common cold, mostly mild symptoms of the upper respiratory system, hoarseness, pharyngitis (not so regularly rhinitis). A peculiar symptom of the infection with the coronavirus is the loss of smell in more than half of patients with mild symptoms. The severer the disease, the higher the percentage of smell loss.[28] In these times, a sudden loss of smell should lead to self-isolation and testing.

After a few days these symptoms of a cold decrease and the so-called viral load falls. One has recovered and is not infective anymore. This happens in general after 5-9 days.[29] Many people have no symptoms at all. In all these cases, the immune system is able to fight the disease.

If this first line of defense in the upper respiratory system is not effective enough, the virus goes down the bronchi, creating cough and a shortness of breath. If the immune system is not able to stop the disease at this level, the consequence is an inflammation of the lungs, a pneumonia. This happens mostly on day 7-9. The Covid pneumonia is often quite severe and might lead to a major damage of the tissues of the lungs[30] with continuing problems for months and may be for lifetime.

A patient with pneumonia is still infective as the immune system had not been able to control the disease. The virus load is still high. Then a switch happens. The immune system that had not been able to fight the disease sufficiently goes into a hyperfunction producing an uncontrolled inflammation, the so-called cytokine storm.[31]  Many deaths, especially in younger people are attributed to this hyper-inflammation. The cortisone Dexamethasone slows down this process and has shown to be of some benefit such cases. [32]

There is some discussion whether one might be infected through the eyes.[33] For sure infection by ingesting viruses is possible, although this seems to be quite rare.

Although not really reliable, some estimates say that approximately 15% of individuals showing symptoms COVID-19 will develop a severe disease, and 5% to 6% will become critically ill.[34]

Why do some people get only slightly ill and some severe?

One reason is the number of viruses one gets infected with. The more viruses one is infected with, the more difficult it is for the immune system to fend off a disease. Some believe that the severity of the disease depends on the so-called ACE2 receptors. As virus needs a door to enter the body, a receptor to dock at, it might create a more severe disease if there are many doors. These doors (ACE2 receptors) are increased in certain diseases as diabetes, hypertension, smoking or COPD.[35] On the other side, young children have fewer receptors in the nose and the upper respiratory system, a fact that some regard as reason why they do not get severely ill.[36]

But all these models are far too simple. Obesity, a major risk factor,[37]  does not increase the ACE2 receptors, nor does pollution.[38] Moreover, it turned out that hypertension with its increased number of ACE2 receptors is not an ‘independent risk factor’ for a severe course of Covid-19.[39] People with risk factors just have very often hypertension, too. Some assume that the blood-group might play a role.[40] But all these factors do not explain why in many patients the immune system that is usually prepared to fight off this coronavirus infection[41] is not able to work appropriately.

The immune system is not an organ

There is much confusion about what the immune system is. For example, patients come and want to boost their immune system. But allergies and auto-immune diseases are a hyperfunction of the immune system. Or as with the Coronavirus, the reduced function of the immune system leads to the disease and its hyperfunction is killing many. There are even indications that a more potent immune system leads to more severe cases of Covid-19.[42]

The problem is that the term immune system does not refer to something specific. It is no integral function. Very different functions and processes are subsumed under the umbrella of the immune system. We might compare it with the security system of a society. It comprises the army, the secret service, the police, but also the street-cleaning, the sewerage disposal, or the aliens department, etc.

To make an example:

A major mechanism to fight respiratory infections is the so-called mucociliary clearance. In the walls of the bronchi there are some cells producing mucus, the goblet cells. This mucus works like a vacuum cleaner. Whatever comes into the lungs sticks to this mucus. Rhythmically moving hair, the cilia of the bronchi, push this mucus towards the throat. If this cleaning system is impaired, due to smoking or pollution,[43] it is much easier to have a more severe course of Covid-19. The environmental pollution might be one of the reasons for the severe development in Bergamo, one of Italy’s most polluted provinces.[44]

During the Covid-19 pandemic only a tiny fraction of the immune system is publicly discussed, the antibodies. We might compare the antibodies with the snipers of the army. They are able to attack a certain microbes quickly and effectively and thus they constitute an important part of the immune system. After an infection the antibodies are still high for some time or even for lifetime, the snipers still patrolling.

In Covid-19 there had been much confusion about these antibodies. The WHO declared that people with antibodies against Covid-19 might not be protected against the disease.[45] That might be true. We do not know it, just as we do not know whether the light in the fridge is out when the fridge is closed. But we should expect it as this is exactly what we see in other diseases. Moreover, antibodies after a vaccination are regarded as the landmark of effectivity.[46] Yet antibodies should not be the sign of the effectiveness of a vaccine.[47] They might not remain for long. In Covid-19 there are indications that antibodies wane after a few months. [48]

Imagine that with a hastily produced vaccine the whole world (seven billion people) is vaccinated in a very short time, as Bill Gates dreams of,[49] but the vaccine has only a duration of a few months and has severe side-effects in 1 of 100.000 people as with the hastily introduced vaccination against swine flu. [50] It would be the perfect medical disaster.

When the antibodies wane, does this mean that we have no protection anymore? No. It is not necessary that the snipers patrol continuously. Some immune cells, the so-called T- memory cells, remember the infection and are able to produce antibodies very quickly if necessary. Moreover, there are other immunologically active cells to fight off such an infection. The presence of some of these cells even allow to predict whether Covid-19 will have a mild or severe form,[51]

It is not even necessary to have had an infection with the same virus to be protected. During a new flu, many elder people had only light symptoms as they had been infected with a comparable or slightly different strain during their youth. [52] This is also how it is explained that during the Spanish Flu the elder people mostly had been spared.[53] Comparingly, people who had an infection with other coronaviruses, only causing a little cold, had been better prepared for the infection with SarsCoV2.[54]  This is a typical example of the hygiene hypothesis. The infection with a lot of germs is good for health.

An infection or a vaccination creates a reaction of the immune system against this or similar diseases. This is called a specific effect. But there are also non-specific effects and the current medical world has a problem with these non-specific effects. This led to the most bizarre of the many bizarre chapters in the medical discourse about Covid-19. It is worth to tell, as it leads to the core of the misunderstanding of medicine by the current medical science.

About 15 years ago a study found that the vaccination against tuberculosis (BCG) and diphtheria, tetanus and poliomyelitis (DPT) lead to a decrease in overall mortality in Burkina Faso, an African country.[55] That is, the vaccinated children did not only perform better in their ability to fight tuberculosis, diphtheria, tetanus or poliomyelitis. All-cause mortality was less. It was correctly assumed that the vaccination produced a specific and a non-specific effect. This unspecific effect lead to some research by the WHO.[56] As it was assumed that this vaccine is able to boost the immune reaction in general,[57] the medical community considered to vaccinate against tuberculosis in order to improve the course of Covid-19 outcomes.[58] Even Tsiodras referred to it in one of his briefings[59] and in South Africa it was even tried it out.[60]

Besides the fact that this idea does not seem to work as a study in Israel suggests,[61] it is a problem to play with the immune system. It might be harmful. For example, a survey found that the vaccination of children in Guinea Bissau, a country a little West of Burkina Faso, lead to an increased all-cause mortality.[62]

Why should one vaccinate with BCG, a notoriously ineffective vaccine[63], in order to provoke an unspecific health effect when body exercise,[64] singing,[65] stress reduction,[66] a lot of psychosocial interventions[67] and many of the naturopathic methods[68] have the same effect? The only reason is that the whole medical community is so obsessed with drugs and vaccinations that they have become unable to think outside their box.

Imagine the following scene: Tsiodras in one of his evening briefings standing up, saying: “Dear fellow citizens at the screens, I want you all to stand up now and to do some exercise with me. Yes, also you grannies on the sofa, come, come. Now we will fight the Coronavirus.” Then singing, dancing and clapping ‘we will, we will rock you’. With his popularity, he could have had a major impact on public health. But he just recommend elders to stay at home, something that will deteriorate their health further[69], or he explained that it might be a good idea when children stay home if there is a person belonging to an susceptible group in the household.[70] He even explained that a heat wave is not caused by the coronavirus.[71]

Infections, inflammation and the immune system

The immune system has to protect the organism against infections, to fight cancer cells, to clear off debris and has many other tasks. One of the means to do all this work is inflammation. Inflammation is not a nuisance or a problem. It is the attempt of the body to solve a problem. All these anti-inflammatory drugs might therefore do much more harm than good as they impede the body’s ability to do its work properly. If the immune system works efficiently, challenges like an infection of light or middle danger are easily encountered. Moreover, with each challenge the immune system learns something for lifetime. It is afterwards better off.

Sometimes the immune system is unable to terminate an infection. The infection becomes chronic and the inflammation continues. Classical examples are the Syphilis, Lyme disease or some forms of viral Hepatitis. At other times although the infection is terminated, the immune system starts to behave inappropriately. A dysfunction might be observed starting with the infection. But, more often, it starts slowly. We might compare this with a family quarrel. Such quarrels are normal. In contrary, families that don’t quarrel are prone to destabilize under demanding conditions. They are not used to face challenges.[72] As a result, families are mostly better off afterwards. Sometimes however, an event cuts deep wounds and alters the behavior of the family. Something fundamentally changes. The relationship becomes dysfunctional. Although everything seems to be fine for the moment, an inner grudge slowly poisons the relationship. Then problems of all sorts arise, and the couple becomes incapable to solve them. Comparingly, many chronic diseases start after an infection. The inflammation does not resolve and leads to all kind of diseases, even to depression,[73]  just as the germ theory describes. In such a case the immune system is no longer able to solve upcoming problems, it has become part of the problem.

Just as we carry a lot of little psychological traumas with us, we have a lot of unresolved inflammations inside us. We see this regularly in the naturopathic treatment. During an effective treatment, people might improve for some weeks or even months and then, suddenly, old problems arise, problems that might had been forgotten for decades. Old wounds hurt, joints get inflamed, a headache which had started after an accident a few decades ago but then vanished, reappears, etc. This is the activation of old inflammations that had never been totally resolved. As soon as the organism works better, it tries to bring these old and unsolved problems in order. In naturopathy we call this ‘from chronic to acute’ and is a sign of an improved health.

Just as with our little psychological scars, we are able to live normally with many of our little inflammations. However, the more of them we have, the more we are more prone to act inappropriately or even decompensate during a major challenge. In older people there is a higher level of inflammation processes.[74] This is one reason why they are more prone for a severe course of Covid-19. But this is not only true for the old. Although children have normally no problem to fight off the Coronavirus, in rare cases their immune system decompensates (the so-called Multisystem Inflammatory Syndrome which resembles the Kawasaki syndrome). There is strong evidence that this immunological decompensation might be the result of a bothered immune system.  But this will be discussed more in detail in the next article.

The virus SarsCoV2 belongs to the germs that creates a major challenge to the immune system. There are severe courses and deaths. Covid-19 is able to affect many organs, might even lead to diabetes.[75] But it is also able to set forth an inflammatory a process leading to chronification. First indications show that the disease might lead, for example, to a broad spectrum of neurological consequences.[76] But there is something very special about Covid. Up to 15% of all Covid-19 patients seem to recover slowly with a clinical picture that resemble chronic fatigue syndrome, a continuous malfunction of the autonomous nervous system probably due to the continuation of an inflammation. [77]

Covid-19 is a perfect example how the germ theory and the hygiene hypothesis are both correct. A virus might cause an acute disease that leads to chronic disease. A good hygiene prevents from becoming ill. It helps to stay resilient (e.g. with less inherent inflammation) and it has many means to recover.

20.7.20

The other articles about the coronavirus pandemic are

  1. The Coronavirus and the Everyday Life in the Quarantine
  2. What does robustness mean in the time of the coronavirus?
  3. Fever and the Use of Antipyretics
  4. After the First Covid-19 Wave – What we have learned and what we have to learn

[1] Brody JE (2020): How to Maintain Motivation in a Pandemic, The New York Times May 18, 2020

https://www.nytimes.com/2020/05/18/well/mind/motivation-pandemic-coronavirus.html?campaign_id=18&emc=edit_hh_20200710&instance_id=20181&nl=well&regi_id=25107315&segment_id=33055&te=1&user_id=40c079be9dfcb373c7c5ade9c3155285

[2]Kutzner F, “Wenn ich mein Verhalten ändere, muss mir das möglichst viel bringen”, Süddeutsche Zeitung, 7.6.20

https://www.sueddeutsche.de/politik/psychologie-und-coronavirus-wenn-ich-mein-verhalten-aendere-muss-mir-das-moeglichst-viel-bringen-1.4925667

[3] Wadman M, Couzin-Frankel J, Kaiser J, Matacic C (2020): How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes, Science Apr. 17, 2020 , 6:45 PM

https://www.sciencemag.org/news/2020/04/how-does-coronavirus-kill-clinicians-trace-ferocious-rampage-through-body-brain-toes#

[4] Meghan E. Sise, M.D., Meridale V. Baggett, M.D., Jo-Anne O. Shepard, M.D., Jacob S. Stevens, M.D., and Eugene P. Rhee, M.D. (2002): Case 17-2020: A 68-Year-Old Man with Covid-19 and Acute Kidney Injury, NEJM DOI: 10.1056/NEJMcpc2002418

[5] Bhayana R, Som A et al. (2020): Abdominal Imaging Findings in COVID-19: Preliminary Observations, Radiology, Published Online:May 11 2020https://doi.org/10.1148/radiol.2020201908

[6] Puelles VG,  Lütgehetmann M et al (2020):  Multiorgan and Renal Tropism of SARS-CoV-2,  NEJM DOI: 10.1056/NEJMc2011400

[7] The Economist (2020): Covid-19 has many faces, May 9th 2020 edition

https://www.economist.com/science-and-technology/2020/05/09/covid-19-has-many-faces

[8] Ivanovas G  (2010): Contributions of Systems – Theory to the Understanding of Therapy and Health, Doctoral thesis at the University of Crete, Medical Faculty p.50

[9] Smith R (2004c): Doctors are not scientists; BMJ  328: 0-h

[10] Smith R (2005b) Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies. PLoS Med 2(5): e138

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0020138

[11] Wikipedia contributors. (2020, April 17). Thomas McKeown (physician). In Wikipedia, The Free Encyclopedia. Retrieved 08:24, June 3, 2020, from https://en.wikipedia.org/w/index.php?title=Thomas_McKeown_(physician)&oldid=951412434

Illich I (1999):  Limits to medicine: Medical Nemisis – the expropration of health Boyars, London

[12] Humphries S, Bystrianyk R (2013): Dissolving Illusions: Disease, Vaccines, and The Forgotten History,  CreateSpace Independent Publishing Platform  pp. 124-141

[13] Covid-19 expert Karl Friston: ‘Germany may have more immunological “dark matter”’, The Guardian 31.5.20

https://www.theguardian.com/world/2020/may/31/covid-19-expert-karl-friston-germany-may-have-more-immunological-dark-matter

[14] Seite „Max von Pettenkofer“. In: Wikipedia, Die freie Enzyklopädie. Bearbeitungsstand: 17. Mai 2020, 16:06 UTC. URL: https://de.wikipedia.org/w/index.php?title=Max_von_Pettenkofer&oldid=200044073 (Abgerufen: 7. Juni 2020, 03:37 UTC)

[15] Ewald PW (2002):Plague Time: How Stealth Infections Cause Cancers, Heart Disease, and Other Deadly Ailments, Anchor Books, New York

[16] Ivanovas G (2010): Contributions of Systems – Theory to the Understanding of Therapy and Health, Doctoral thesis at the University of Crete, Medical Faculty, p. 164

[17] https://www.zeit.de/2017/29/depressionen-chronische-entzuendungen-psychologie-forschung

[18] Watts G (2004): The defence of dirt, BMJ 328: 1226

Ivanovas G (2010): Contributions of Systems – Theory to the Understanding of Therapy and Health, Doctoral thesis at the University of Crete, Medical Faculty, σελ. 102

[19] Kostic AD, Xavier, RJ,  Gevers D (2014): The Microbiome in Inflammatory Bowel Disease: Current Status and the Future Ahead, Gastroenterology 146, 6: 1489-1499

[20] Scales B, Huffnagle GB (2012): The microbiome in wound repair and tissue fibrosis, J. Pathol., 229: 323-331. doi:10.1002/path.4118

[21] Korpela, K., Salonen, A., Virta, L. et al. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun 7, 10410 (2016). https://doi.org/10.1038/ncomms10410

Iwase, T., Uehara, Y., Shinji, H. et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465, 346–349 (2010). https://doi.org/10.1038/nature09074

[22] Alcock, J., Maley, C.C. and Aktipis, C.A. (2014), Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. BioEssays, 36: 940-949. doi:10.1002/bies.201400071

[23] Valles-Colomer, M., Falony, G., Darzi, Y. et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol 4, 623–632 (2019). https://doi.org/10.1038

[24] More Evidence Links Gut Bacteria to Dementia – Medscape – Feb 06, 2019.

https://www.medscape.com/viewarticle/908769

Jiah Pearson-Leary, Chunyu Zhao, Kyle Bittinger, Darrell Eacret, Sandra Luz, Abigail S. Vigderman, Gabriel Dayanim, Seema Bhatnagar. The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats. Molecular Psychiatry, 2019; DOI: 10.1038/s41380-019-0380-x

[25] Planas R, Santos R, Tomas-Ojer P, et al.: GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis. Science Translational Medicine, 10 Oct 2018. doi: 10.1126/scitranslmed.aat4301

[26] Alavi S, Mitchell JD et al. (2020): Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection. Cell, 2020; 181 (7): 1533 DOI: 10.1016/j.cell.2020.05.036

[27] Stothart Mason R., Bobbie Colleen B., Schulte-Hostedde Albrecht I., Boonstra Rudy, Palme Rupert, Mykytczuk Nadia C. S. and Newman Amy E. M. (2016): Stress and the microbiome: linking glucocorticoids to bacterial community dynamics in wild red squirrelsBiol. Lett.1220150875

[28] Whitcroft KL, Hummel T. Olfactory Dysfunction in COVID-19: Diagnosis and Management. JAMA. 2020;323(24):2512–2514. doi:10.1001/jama.2020.8391

[29] Zou L, Ruan F et al. (2020): SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients, n engl j med 382;12

[30] Kommoss FKF, Schwab C, Tavernar L, Schreck J, Wagner WL, Merle U, Jonigk D, Schirmacher P, Longerich T: The pathology of severe COVID-19 related lung damage— mechanistic and therapeutic implications. Dtsch Arztebl Int 2020; 117: 500–6. DOI: 10.3238/arztebl.2020.0500

[31] Sinha P, Matthay MA, Calfee CS. Is a “Cytokine Storm” Relevant to COVID-19? JAMA Intern Med. Published online June 30, 2020. doi:10.1001/jamainternmed.2020.3313

[32]  Johnson RM, Vinetz JM. Dexamethasone in the management of covid -19 BMJ 2020; 370 :m2648

[33] Can You Catch COVID-19 Through Your Eyes? – Medscape – May 26, 2020.

https://www.medscape.com/viewarticle/931145?nlid=135722_4663&src=WNL_mdplsnews_200529_mscpedit_fmed&uac=290363HR&spon=34&impID=2399612&faf=1

[34] Schaller T, Hirschbühl K, Burkhardt K, et al. Postmortem Examination of Patients With COVID-19. JAMA. 2020;323(24):2518–2520. doi:10.1001/jama.2020.8907

[35] Alqahtani JS, Oyelade T et.al (2020): Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis, PLOS One, May 11, 2020 https://doi.org/10.1371/journal.pone.0233147

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233147

[36] Tsiodras Evening Bulletin 21.5.20

Bunyavanich S, Do A, Vicencio A. Nasal gene expression of angiotensin-converting enzyme 2 in children and adults. JAMA. Published online May 20, 2020. doi:10.1001/jama.2020.8707

[37] Petrilli CM, Jones SA et al. (2020): Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study BMJ 2020; 369 :m1966

https://www.bmj.com/content/369/bmj.m1966

[38] https://www.ethnos.gr/ellada/109811_kathigitis-apth-i-atmosfairiki-rypansi-enishyei-nosirotita-kai-thnitotita-apo-ton

[39] Grasselli G, Greco M, Zanella A, et al. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med. Published online July 15, 2020. doi:10.1001/jamainternmed.2020.3539

Williamson, E.J., Walker, A.J., Bhaskaran, K. et al. OpenSAFELY: factors associated with COVID-19 death in 17 million patients. Nature (2020). https://doi.org/10.1038/s41586-020-2521-4

[40] Ellinghaus D, Degenhardt F, Bujanda L et al. (2020): Genomewide Association Study of Severe Covid-19 with Respiratory Failure, N Engl J Med. 2020 Jun 17:NEJMoa2020283. doi: 10.1056/NEJMoa2020283

[41] Thevarajan, I., Nguyen, T.H.O., Koutsakos, M. et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 26, 453–455 (2020). https://doi.org/10.1038/s41591-020-0819-2

[42] Mathew D, Giles JR et al. (2020): Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications, Science  15 Jul 2020: eabc8511 DOI: 10.1126/science.abc8511

[43] Wang M, Aaron CP, Madrigano J, et al. Association Between Long-term Exposure to Ambient Air Pollution and Change in Quantitatively Assessed Emphysema and Lung Function. JAMA. 2019;322(6):546–556. doi:10.1001/jama.2019.10255

[44] Setti L, Passarini F, et al. (2020): SARS-Cov-2 RNA Found on Particulate Matter of Bergamo

in Northern Italy: First Preliminary Evidence, medRxiv preprint https://www.medrxiv.org/content/10.1101/2020.04.15.20065995v2

[45] https://www.who.int/news-room/commentaries/detail/immunity-passports-in-the-context-of-covid-19

[46] Π.χ.: https://www.ft.com/content/65d0b33a-f12a-4878-ac87-da4835683949

https://www.theguardian.com/society/2020/may/18/first-human-trial-results-raise-hopes-for-coronavirus-vaccine

[47] Lurie N, Sharfstein JM, Goodman JL. The Development of COVID-19 Vaccines: Safeguards Needed. JAMA. Published online July 06, 2020. doi:10.1001/jama.2020.12461

[48] Long, Q., Tang, X., Shi, Q. et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med (2020). https://doi.org/10.1038/s41591-020-0965-6

Seow J, Graham C et al. (2020): Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection, medRxiv 2020.07.09.20148429; doi: https://doi.org/10.1101/2020.07.09.20148429

[49] https://www.gatesnotes.com/Health/What-you-need-to-know-about-the-COVID-19-vaccine

[50] Lurie N, Sharfstein JM, Goodman JL. The Development of COVID-19 Vaccines: Safeguards Needed. JAMA. Published online July 06, 2020. doi:10.1001/jama.2020.12461

[51] Liu J, Li S et al. (2020): Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients, EBioMedicine  DOI: 10.1016/j.ebiom.2020.102763

[52] Bingyi Yang, Justin Lessler et al. (2020): Life course exposures continually shape antibody profiles and risk of seroconversion to influenza. PLOS Pathogens, 2020; 16 (7): e1008635 DOI: 10.1371/journal.ppat.1008635

[53] Gostic K, Ambrose M, Worobey M, Lloyd-Smith JO (2016): Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting, Science11 Nov 2016 : 722-726

[54] Braun, J., Loyal, L., Frentsch, M. et al. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature (2020). https://doi.org/10.1038/s41586-020-2598-9

Kreer, C., Zehner, M. et al. (2020):  Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients, Cell, doi: https://doi.org/10.1016/j.cell.2020.06.044

[55] Vaugelade J, Pinchinat S, Guiella G, Elguero E, Simondon F (2004): Non-specific effects of vaccination on child survival: prospective cohort study in Burkina Faso, BMJ 329:1309

[56] Higgins JPT, Soares-Weiser K, Reingold A (2014): Systematic review of the non-specific effects of BCG, DTP and measles containing vaccines

https://www.who.int/immunization/sage/meetings/2014/april/3_NSE_Epidemiology_review_Report_to_SAGE_14_Mar_FINAL.pdf

WHO Working Group (2020): Evidence based recommendations on non-specific effects of  BCG, DTP-containing and measles-containing vaccineson mortality in children under 5 years of age,

https://www.who.int/immunization/sage/meetings/2014/april/1_NSE_Backgroundpaper_final.pdf?ua=1

[57] University of Bonn. (2020, June 15). Tuberculosis vaccine strengthens immune system. ScienceDaily. Retrieved July 4, 2020 from www.sciencedaily.com/releases/2020/06/200615140855.htm

[58] Curtis N, Sparrow A, Ghebreyesus TH, Nete MG (2020): Considering BCG vaccination to reduce the impact of COVID-19, The Lancet April 30, 2020DOI:https://doi.org/10.1016/S0140-6736(20)31025-4

[59] Tsiodras Evening Bulletin 8.5.20

[60] https://www.africanews.com/2020/05/05/south-africa-trial-using-tb-vaccine-against-covid-19/

[61] Hamiel U, Kozer E, Youngster I. SARS-CoV-2 Rates in BCG-Vaccinated and Unvaccinated Young Adults. JAMA. Published online May 13, 2020. doi:10.1001/jama.2020.8189

[62] Kristensen I, Aaby P, Jensen H (2000): Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa.  BMJ  321: 1435-39

[63] Nemes E, Geldenhuys H et al. (2018): Prevention of M. tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination, N Engl J Med. 2018 Jul 12;379(2):138-149. doi: 10.1056/NEJMoa1714021.

[64] Nieman DC. Exercise, upper respiratory tract infection, and the immune system. Medicine and Science in Sports and Exercise. 1994 Feb;26(2):128-139. DOI: 10.1249/00005768-199402000-00002.

Romeo, J., Wärnberg, J., Pozo, T., & Marcos, A. (2010). Physical activity, immunity and infection. Proceedings of the Nutrition Society, 69(3), 390-399. doi:10.1017/S0029665110001795

[65] Kreutz G, Bongard S, Rohrmann S, Grebe D, Bastian HG, Hodapp V (2004): Effects of choir singing or listening on secretory IgA, cortisol, and emotional state, Journal of Behavioral Medicine, 27; 6: 623-635

Stacy R, Brittain K, Kerr S (2002): Singing for health: an exploration of the issues, Health Education, Vol. 102 No. 4, pp. 156-162. https://doi.org/10.1108/09654280210434228

[66] Alessi, MG, Bennett, JM. Mental health is the health of the whole body: How psychoneuroimmunology & health psychology can inform & improve treatment. J Eval Clin Pract. 2020; 1– 9. https://doi.org/10.1111/jep.13386

[67] Shields GS, Spahr CM, Slavich GM. Psychosocial Interventions and Immune System Function: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Psychiatry. Published online June 03, 2020. doi:10.1001/jamapsychiatry.2020.043

[68] Kreutzfeldt A, Müller K (2001): Verbesserung der Immunregulation durch Methoden der Physikalischen Therapie, Phys Rehab Kur Med 2001: 188-195

Kreutzfeldt A, Albrecht B, Müller K (2003): Einfluss des Wassertretens nach Kneipp auf die Immunregulation, Phys Rehab Kur Med 2003

[69] Bowden Davies, K. A., Pickles, S., Sprung, V. S., Kemp, G. J., Alam, U., Moore, D. R., … Cuthbertson, D. J. (2019). Reduced physical activity in young and older adults: metabolic and musculoskeletal implications. Therapeutic Advances in Endocrinology and Metabolism. https://doi.org/10.1177/2042018819888824

[70] Evening Bulletin 14.5.20

[71] Evening Bulletin 15.5.20

[72] Minuchin S,Fishman CC (1981): Family Therapy Techniques. Harvard University Press, Cambridge, Mass. p. 22

[73] Engler, H., Brendt, P., Wischermann, J. et al. Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms. Mol Psychiatry 22, 1448–1454 (2017). https://doi.org/10.1038/mp.2016.264

[74] Max-Planck-Gesellschaft. “Changes in the immune system can promote healthy aging.” ScienceDaily. ScienceDaily, 10 July 2020. www.sciencedaily.com/releases/2020/07/200710121810.htm

[75] Rubino F, Amiel SA et al. (2020): New-Onset Diabetes in Covid-19, N Engl J Med. 2020 Jun 12:NEJMc2018688. doi: 10.1056/NEJMc2018688

[76] Paterson RW, Brown RL et al. (2020): The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings, Brain, , awaa240, https://doi.org/10.1093/brain/awaa240

Ameres, M., Brandstetter, S., Toncheva, A.A. et al. Association of neuronal injury blood marker neurofilament light chain with mild-to-moderate COVID-19. J Neurol (2020). https://doi.org/10.1007/s00415-020-10050-y

[77] Reddy S (2020): Three Months In, Still Ravaged By Covid’s Fallout, Wall Street Journal July 1, 2020 10:00 am ET

https://www.wsj.com/articles/three-months-in-these-patients-are-still-ravaged-by-covids-fallout-11593612004?mod=searchresults&page=1&pos=1

Carfì A, Bernabei R, Landi F, for the Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. Published online July 09, 2020. doi:10.1001/jama.2020.12603