When I started my medical office in Crete 1993 allergies and auto-immune diseases in children were a rarity. This has changed radically. Allergies are on the rise.[1] Current estimates for Crete assume that 10% of the children have asthma 7% of the adults,[2] or 8% for the general population of Greece.[3] But everyday experience suggests a much higher number and international research talks of an incidence of 20% and even more.[4] Why did and does this happen?
The case of Michalis
In an article in one of the major medical Journals of the world (The New England Journal of Medicine), Eva Mantzouranis, then associate professor of pediatrics at the University of Crete, described in the year 2008 the case of the 4 year old Michalis from a Cretan village who developed asthma.[5] She attributed his disease to air pollution with open fire cooking, passive smoking (the father was a heavy smoker), biomass fuels from an olive press and the exhaust fumes from agricultural machines. There is lot of evidence that there is a point in her hypothesis as pollution is linked to higher numbers of asthma.[6] The same is true for smoking.[7] Even living at roads with a lot of traffic leads to a higher probability of asthma.[8] But this cannot be the whole story. Still 20 years ago, the internationally known “Athens paradox” said that there was a low prevalence of Asthma and allergies in Athens despite a high level of pollution.[9] Something more fundamental has happened with the immune system the last decades. Not only asthma is continuously on the rise, there is also growing number of auto-immune diseases,[10] for example Crohn disease,[11] autoimmune thyroiditis[12] and others.
Ms Mantzouranis stated in her article that pollution must be the cause for Michali’s asthma as “most aspects of Michael’s village have not changed for hundreds of years”[13] Living myself in a Cretan village since 1992 I cannot agree with her statement. In the period before the Olympic games, when Michalis was born, many factors had already changed in the villages, for example, diet. Such a change of nutrition has a major effect onto the immune system.[14] In the villages they did no longer follow the traditional Mediterranean diet. They ate processed food, often of the worst kind. In order to do something for their health, village people drank a glass of milk every day. It took me quite a time to find out what they meant – as fresh milk was unknown in the villages. A glass of milk was a glass of water with a shot of NOUNOU, a white, canned, fatty and sugary liquid, called condensed milk, only available in Greece. The health benefit of this NOUNOU water was even advertised in the TV and the TV played continuously. This was the health education of villagers, training them for a life according to the principles of BIG FOOD, as the food producing industry is called[15]. The obesity epidemics[16] raging now in Greece, started during these years.[17]
All this is important for the yet unborn Michalis, as mother’s nutrition even before conception plays a role for the health of a child.[18] Asthma seems to depend partly on the maternal nutrition before becoming pregnant.[19] Of course nutrition during pregnancy plays an important role for the development of the immune system of the child, too,[20] and village people did not care a lot about a healthy nutrition.
Drugs are another major change in the village life of last 50 years and drugs taken by the mother during pregnancy are important for the immune system of the unborn. Here just two examples of a long list.
- Paracetamol during pregnancy might increase the risk for asthma in the child.[21] Depon (Tylenol, Panadol and others) had been a basic item of every village convenience store and had been taken like vitamins by many villagers.
- Acid suppressing medications taken during pregnancy increase the risk of asthma in the child. They were and are prescribed quite often for pregnant women.[22]
These acid suppressing medications are of special interest, as one class of them, the Proton Pump Inhibitors (PPI), are regularly given to babies when they have digesting problems or heartburn. These drugs influence the immune system by changing the gut flora.[23] They increase the risk of pneumonia,[24] and they might even, although rarely, lead to fractures in children.[25] They are also related to a more severe course of a Coronavirus infection.[26] Generally it is striking how many of these factors that changed in the villages between 1980 and 2004 make more prone for a severe course of Covid-19.
Another major change in the last 50 years are Caesarean births. They lead to a reduced bacterial flora and are associated with a poorer function of the immune system.[27] The WHO regards more than 10-15% of Caesarean births as not medically justified.[28] The Greek reality is a section rate around an unacceptable 50%.[29]
Breastfeeding, which is helpful against asthma and improves immunological development in general,[30] was at an all-time low at the time when Michalis was born. Hospitals then were institutions to discourage breast-feeding. During that period, I visited a friend who had given birth to her first child a few hours before. Within half an hour the gynecologist found three reasons why the new mother should give foreign milk to her baby, with the grandmother heavily supporting this request. This was not a single case, but everyday reality. Luckily at least this has changed for better since then.
The first solid food introduced to the babies’ diet plays an important role for the immune competence of children later.[31] Then there was the general advice from many pediatricians, but also from the University hospital, to give daily either meat or egg. This is a poor diet, spoiling the gut flora even more. This bad first diet might be another factor for the current obesity epidemics.[32] Moreover, children were given all these sweetened teas and drinks, all available in the village convenience store, priming them on a sweet taste, leading them later to a sugar consumption of more than 100gr a day.[33] For example, these nice fruit yoghurts (not available in the villages then) with their appealing pictures contain up to 15% of sugar and the fine morning cereals contain up to 25%.[34] BIG FOOD even regards 30% of sugar or fat in cereals as “balanced”.[35] A tart in the kinder garden for some anniversary or names day was the rule, not the exception.
Sugar impedes directly the immune function[36] and is a main reason for the obesity in children.[37] Obesity is related with a higher insulin resistance which marks the first step for diabetes.[38] It is also responsible for an estimated quarter of all asthmatic diseases in children[39] and is one of the major risk factors for Covid-19.
Obesity is such an important risk factor in Covid-19 as it causes a chronic state of inner inflammation.[40] These inflammations are a reason why especially the elder people have severe courses of Covid-19.
Another major change in the villages are the use of plastic items. Plastics evaporate chemicals, called endocrine disrupters. These chemicals disturb the hormonic function. They lead to obesity[41] and impair the immune system.[42]
Another major change during these years is vaccinations. Vaccination is a delicate subject as it has become a topic provoking strong emotions. A kind of religious zeal prevails in debates. Scientific analysis is rare. Vaccinations provoke a reaction of the immune system. This is their purpose. To do so, many vaccines contain immunologic enhancers. These enhancers influence, as the name says, the immune system. Aluminium, mercury and others are probably responsible for the so-called non-specific effects of vaccines. These effects have been widely discussed as protective during the Covid-19 pandemic (BCG vaccination). We do not know much about these immunological enhancers. They might improve health,[43] and even prevent Alzheimer disease.[44] Logically, they might also have a negative effect.[45] As in the last 20 years the vaccination program has substantially increased and starts earlier during life, there is the question in how far this kind of immune stimulation might contribute to the development of chronic diseases. There are, indeed, some indications that they might play a role in the increase of immunological disorders like asthma.[46]
These are just a few of the many factors that might explain why the immune system does not work properly anymore in today’s children and adolescents. We do not know in how far these factors apply to Michalis. We do not know, either, whether Michalis was obese when he was diagnosed with asthma. The probability that he is obese today, he must be in the high school right now, is very high.
What we know, however, from Michalis’ health record is that he suffered regularly from bronchial infections and most of them will have been treated with antibiotics. If not prescribed by the physician, people bought it by their own as self-medication with antibiotics in rural Greece was very high.[47] Antibiotics are harmful for the gut flora[48] and increase obesity.[49] Moreover, they are superfluous in most bronchial infections.[50] We also know that Michalis had been described sprays to control the symptoms of his asthma, but probably never received health promoting measures. Therefore, Michalis might already belong to the susceptible group for Covid-19.[51]
Covid and Asthma
It had been assumed that asthma predisposes for a more severe course of Covid-19. There is a lot of evidence pointing into this direction. People with asthma are more prone to suffer from viral infections and they tend to have a more severe outcome with common cold viruses. [52]
The symptoms of asthma are mostly controlled by bronchodilatation drugs and cortisone, as prescribed to Michalis. Especially cortisone increases the risk of viral infections of the respiratory system and make them severer[53], either given topically[54] or in oral form.[55]
Astonishingly people suffering from asthma are under-represented in the severe courses of Covid-19.[56] There are different explanations for this finding. For sure, asthmatic persons are more cautious. Discussed is also a beneficial effect from cortisone as it reduces the hyperinflammation seen in severe cases of Covid-19. The official advice for people with asthma is to stay on steroids, [57] but to use the lowest possible dose to avoid exacerbation,[58] as the beneficial effect of cortisone depends on the dosage.[59] A higher dose of cortisone leads to more severe courses. In contrast to asthma, the benefits of inhaled corticosteroids in COPD patients are less clear and they should be avoided unless the patients are very symptomatic. Moreover, COPD patients tend to have more severe courses of Covid-19[60] as the cleaning mechanism, the mucociliary clearance is damaged.
Although this news is soothing for asthmatics, it might be just a statistical accident. We often see that first preliminary results give a different picture than a more solid statistical analysis with a larger number of patients. For example, hypertension was accused to be a major risk factor for Covid-19. Newer research does not support this impression anymore. It was just an accidental finding as people with risk factors have often also hypertension.[61]
Covid in Children
When the pandemic started there was the comforting news from China that the disease would not affect children, or if, they would only have minor symptoms. Then rumors started that children with Covid-19 were hospitalized with a mysterious illness,[62] resembling the Kawasaki syndrome. Kawasaki disease is not that rare. In Greece there several dozen cases every year.[63] But during the first phase of the Coronavirus pandemic the syndrome appeared 30 times more often,[64] and some of these children died.[65] It was not like the usual Kawasaki syndrome, but is today regarded as a different, new disease, called the Multisystem Inflammatory Syndrome, or pediatric multisystem inflammatory syndrome (PIMS) or pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS).[66] It has been described as “a serious and life-threatening illness in previously healthy children and adolescents associated with a SARS-CoV-2 infection”.[67] The known cases might only be the tip of the iceberg,[68] as only children with severe symptoms were diagnosed.
The Multisystem Inflammatory Syndrome does not appear during the infection. It is ‘postinfectious,’ probably due to an abnormal immune response after the viral infection.”[69] That is, this disease is just another immunological disorder where, due to an infection, the immune system overreacts and creates a wide range of symptoms.[70] Probably it will become diagnosed more often in the future as the immune system of the children tends to deteriorate continuously and it might not be only caused by SarsCoV2, but other viruses as well.
The other articles about the coronavirus pandemic are
- The Coronavirus and the Everyday Life in the Quarantine
- What does robustness mean in the time of the coronavirus?
- Fever and the Use of Antipyretics
- After the First Covid-19 Wave – What we have learned and what we have to learn
- Understanding Covid-19
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