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Covid-19 and the Local Defense

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

Health is an orphan in current medicine. It is an orphan sitting in a corner who’s presence is occasional acknowledged and then shouted at. Stop smoking! Move a bit more! Lose weight! All this is not especially helpful. An even more neglected orphan is the topic of the local immune function or local resistance.

In the case of the Coronavirus, local resistance concerns mainly the function of the respiratory system. Other ways of infection are possible, but rare. Understanding the protective mechanisms of the respiratory system helps to support them in the case of an infection with the coronavirus SarsCoV2 or as preventive measure.  But let us start with the skin.

The local defense of the skin

The skin is affected in about 2% to 20% of patients with Covid-19.[1] This happens because the skin possesses the so-called ACE2 receptors. Theoretically an infection with coronavirus through the skin should be possible, although it is questionable whether this happens.[2] The skin has good protective mechanisms. It separates much better the inner of the body from the outer world compared to the mucosa of the respiratory tract or the digestive system. But the skin and the mucosa share common principles.

Many children suffer from the bacterium Staphylococcus aureus (Impetigo) and they do so mostly in summer. In general, people think this happens because the child gets infected at this very moment. It might be so. Some children also infect some of their siblings, but rarely their parents. This does not happen because the parents don’t catch the bacterium. They are exposed to it. It just does not do any harm to them. About 50% of people and up to 90% of health care professionals have this bacterium as a normal inhabitant on their skin. Germs that might or might not create a problem are called facultative pathogens. Depending on the function of the skin a bacterium might be neutral, or friendly or it might become harmful. That is, Impetigo is not about the bacteria alone, it is also about the function of the skin.

A healthy person is inhabited by 10.000.000 germs on every square centimeter skin.[3] We live fine with all these bacteria, viruses and fungi, even with the Staphylococcus aureus. Only under certain circumstances, when the local immune defense is deteriorated, the bacterium will proliferate and create the picture of Impetigo.

Many factors influence the local immune defense of the skin. Nutrition, the gut flora, the hormonic regulation, exercise, in short, all life-style factors play a role. Children are infected more easily as their hormonic system and therefore the function of the skin is different. [4] As the Staphylococcus likes a moist atmosphere, children mainly become symptomatic in summer.

Staphylococcus aureus often starts to proliferate on wounds, that is, at places where the integrity of the skin is traumatized. Through scratching the skin is further traumatized and the germ is transferred to other parts of the body.

In general, the organism can cope with such a damage.  Affected spots heal on their own. Skin healing is a complex phenomenon [5] only partly understood.[6] When the healing process is impaired, the Staphylococcus proliferates, and we might see terrible pictures.

The usual treatment with local antibiotics kills the bacterium at the applicated places. This does not mean that the microbe vanishes. The reduction of its number, however, gives the healing mechanisms the chance to do their work. If these mechanisms do not work properly, the infection persists or might spread despite the local antibiotic therapy. A phototherapeutic treatment with, let’s say propolis, although effective against the germ,[7] might not be that effective in killing the bacteria. But Propolis improves the function of the skin and its local defense more generally.[8] This is a better middle and long-term strategy.

Parents often use Betadine or another antiseptic to treat Impetigo. In my experience this makes things worse. Healing depends on a healthy skin flora. [9] Antiseptics just destroy this flora, for example also the bacterium Staphylococcus epidermidis, a cousin of the Staphylococcus aureus. Staphylococcus epidermidis inhibits and kills Staphylococcus aureus and supports the healing process.[10] It is also helpful against many other infections, e.g., the HPV virus.[11]

Harming the microbiome has many long-term disadvantages that still are not taken seriously enough from the medical world. This is especially true for the oral antibiotics that are given, when the Impetigo has covered a larger part of the body. We should be cautious and not give them unnecessarily for skin affections. For example, research does not support a positive effect of antibiotic therapy for chronic wound healing.[12]

In Covid-19, some dermatologists uttered the concern that masks, gloves and other protective measures might mechanically disturb the integrity of the skin, thus making the skin more vulnerable.[13] Moreover, all these disinfectants distort the microbiome, and both might be an important factor to facilitate a percutaneous infection with SarsCoV2.[14]

This concern might be a bit exaggerated, but it is a good example of how the local defense might be impaired, also of the respiratory system.

 The local defense of the nose

The nose is a neglected organ. Normally it is just seen as two pipes with our main task is to keep these pipes open, just like with the drain of the kitchen sink. If clogged, we must unblock them mechanically or chemically. Nothing could be more wrong than this view.

The nose and paranasal sinuses cover an area of 100-200 cm2 and about 10 000-15 000 l air flow daily through a healthy nose.

In the nose’s entrance hair filters bigger particles. In the first part of the nose a thick mucus is produced, able to trap substances and germs. Deeper inside we find the mucociliary system, the common cleaning mechanism of all the respiratory tract (nose, paranasal sinuses, bronchi, ears). Certain cells, the Goblet cells produce a mucus and the cilia of the epithelium push them forward.

This mucus consists of two layers, one is thinner to allow the movement of the cilia. The other layer is thicker to catch small particles and germs. The mucus has antimicrobial compounds [15] and the cilia move quicker when they have contact with foreign bacteria.[16] That is, the cleaning mechanism reacts to infections and works according to the needs of the immune defense. These two videos demonstrate the function of the muco-ciliary cleaning system

https://www.youtube.com/watch?v=HMB6flEaZwI

https://www.youtube.com/watch?v=Zi9RcyYbeGc&t=110s

We should be aware that the mucus is the attempt of the body to solve a problem. It is not the problem on its own.

To improve the function of the nose most people use physiological saline solution or a comparable nasal douche. The nasal rinse removes mucus and other matter. It increases hydration of the deeper aqueous layer, thereby improving underlying ciliary beat frequency and reducing local inflammatory substances.[17] This is the theory. In practice some parents are obsessed with nasal rinse, using half a liter or more a day. No mucusς is so much irritated as the nasal. Even vacuum cleaners are used to clean the nose, although the mucociliary system is directed into the other direction, towards the esophagus.[18] Comparingly to the skin, this mechanic damage might make the nose more prone for a viral infection. Moreover, all these practices also disturb the flora of the nose.

Just as with the skin, the flora of the nose is of major importance for the local immune defense. There are facultative pathogens, for example the well-known Staphylococcus aureus. In the nose, the role of the good guy has the Staphylococcus lugdunensis.[19] Comparingly to the skin, the nasal microbiome influences viral infections,[20] for good or for bad. The susceptibility to influenza infection depends on the microbiome of the nose (and throat) at the time of exposure.[21]

The flora of the nose also plays an important role in the development of chronic diseases. Asthma and allergies strongly depend on a healthy nose[22] and probiotics are known to reduce allergic symptoms.[23]

The sinuses also contribute to the immune defense,[24] although their function is not totally clear until today.

Another strange mechanism is the nasal cycle, which is part of immune defense, too.[25] The nose congests and decongests on one side and then on the other side approximately every 3 hours, leading to an alternate airflow between the two nostrils.[26]

The sad reality is that there are so many problems with the health of the nose. A clogged nose is a well-known topic in small children (snotty nose). If not chronic, there is no problem with this repeating rhinitis as children have to encounter many (mainly viral) infections. These infections educate the immune system and help to train it for more severe infections.[27] The often-seen adenoids are nothing else than augmented immunological tissue. They are a sign that the immune system struggles, but it is not necessarily a bad sign. To keep the nose technically open does not solve any immunological problem and the removal of adenoids, for example, tends not to be helpful for children’s’ health in the mid- and long-term.[28] More important is to improve the function of the immune system of the children locally and generally.

Many environmental factors disturb the nasal health, like pollution, too dry and too warm sleeping rooms (they should not be over 18 degrees in winter), too little contact with fresh air and many others. But probably nothing harms so much as the excessive nasal rinse and all these nasal decongestants.

The decongestants impede the local immune function, they alter the flora, they do little to improve a cold and they might have severe side effects. The international advice is not to give nasal decongestions to children under the age of 6, as even deaths due to their use have occurred.[29]

All this gives us an idea of how to face a Coronavirus infection. Cautious nasal rinsing might be helpful.[30] Inhalations (see below) and other health measures might improve the local immune function and the clearing mechanism or the nasal flora. Alternating temperatures, exercise and so many other activities influence the nasal function for good in order to prevent a severe course of Covid-19. But the only thing the medical world came up with was to treat the nose with iodine (e.g., Betadine) as it quickly inactivates the SarsCoV-2 virus. [31]

 The local defense of the mouth

The oral microbiome has a similarly important impact on health.[32] Its quality depends on life-style factors like nutrition. Sugar is especially damaging.[33] Smoking and vaping not only disturb the microbiome profoundly or damage the mucosa. They also lead to periodontitis,[34] with tooth sanity as another important factor for the oral microbiome and for the local immune response.[35]

The mouth itself does not possess such sophisticated immune measures like the nose or the bronchi. The guards are situated deeper inside. At the entrance of the throat there are protective immune tissues (Waldeyer’s tonsillar ring) part of which are the tonsils.

These tissues protect the lower respiratory system from many health threats and are especially important during a Coronavirus infection. The pharynx and the salivary glands are a major sources of coronavirus replication. If the local defence does not work correctly, the viral load will be higher, and the disease will spread more easily to the bronchi. A high viral load of the mouth makes the person more infective for others, too. [36] This is why the care of the mouth and the nose play such an important role in Covid-19.

It had been discussed in how far mouth washing might be beneficial to prevent an infection with the Coronavirus. Many different substances had been tested, including the notorious iodine (Betadine). [37] Most of the commercially available oral rinses inactivate the Coronavirus, at least in the laboratory. Among the tested was also a rinse based on essential oils.[38] Theoretically, propolis should have a similar good effect but had not been tested yet.

Even when the infection with the Coronavirus goes deeper inside the bronchi, mouth’s sanity is still important. Bacteria coming from the mouth might lead to a bacterial superinfection in the lungs. Especially Staphylococcus aureus is feared,[39] and its presence depends on the microbiome of the mouth.

The local defense of the bronchi and the lower respiratory tract

The local defense of bronchial system follows the already discussed principles. A functioning mucociliary clearance and a healthy microbiome are important. The bronchial microbiome depends on the microbiome of the upper respiratory tract as the bacteria of the nose and the mouth disperses into the bronchi.[40] The only difference is that there are less microbes in the bronchi. [41]

Wherever we look, we see the same motive. Lifestyle factors, like nutrition and exercise play an important role in the resilience of the bronchial system. This has been extensively investigated in asthma.[42] Even the microbiome of the gut stimulates the function of the lungs and the bronchi.[43] It is fascinating, how all these different functions are so minutely connected.

Obviously smoking[44] and vaping[45] heavily disturb these defense mechanisms, they disturb the mucociliary clearance, might traumatize the bronchi and make more prone for a severe course of Covid-19.

How to improve the local defense mechanisms

The measures to improve our health and our immune system to be more fit for a coronavirus infection are quite simple. It is a healthy lifestyle. Nutrition provides the nutrients for a good function of the body. It improves the microbiome which improves the immune function. Fresh air and exercise in a natural environment keep the respiratory system in a good shape. Sleep provides the necessary maintenance of all organs and is important for local repair mechanisms, and so on. All these are the principles of hygiene.

More specific measures to prevent a viral infection like that of the SarsCoV2 virus are drug based immunostimulants (discussed in the former article).

During a pharyngitis or a sore throat, it is a good idea to treat locally. Oral rinses might be helpful. The better they cope with the local microbiome, the higher their benefit. Probably plant based rinses are better. Even gargling with sage tea might be protective.

Probiotics might improve the local microbiome and the local immune defense. But they should not be used mechanically. There should be a clear idea why they are necessary and what their aim should be.

A good therapeutic measure is inhalation. It might be done just with saline solution or with herbs. Herbs should only cautiously be used. A very light herbal tea is fine for inhalation. The process of inhalation leads to a better clearance of the nose and the bronchi, just as described above for the saline solution of the nose. But inhalation has the advantage not to irritate the mucosa.

The traditional style of inhaling (over a pot with a towel) has further advantages. It not only improves the function of the mucociliary clearance. The heat and the water on the face stimulate a reactive process that improves the local function of the mucosa.

Such reactive processes are also the main aim of the footbaths. Typically, an increasing-temperature foot bath leads to a running nose during a rhinitis and often a clogged nose just opens. That is, local functions can be stimulated with interventions on other parts of the body.

There are many ways to start with. In trying out different techniques one quickly realizes what fits best to oneself. The first step, however, is to take responsibility for the own health.

 

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
  5. Understanding Covid-19
  6. Covid-19 and the Battered Immune System
  7. Facing the Coronavirus – Taking on Responsibility

 

[1] Ring J. (2020). The skin in the era of coronavirus pandemic. Journal of the European Academy of Dermatology and Venereology : JEADV, 34(7), 1384–1385. https://doi.org/10.1111/jdv.16718

[2] Xue, X., Mi, Z., Wang, Z., Pang, Z., Liu, H., & Zhang, F. (2020). High Expression of ACE2 on Keratinocytes Reveals Skin as a Potential Target for SARS-CoV-2. The Journal of investigative dermatology, S0022-202X(20)31602-X. Advance online publication. https://doi.org/10.1016/j.jid.2020.05.087

[3] SanMiguel, A., & Grice, E. A. (2015). Interactions between host factors and the skin microbiome. Cellular and molecular life sciences : CMLS, 72(8), 1499–1515. https://doi.org/10.1007/s00018-014-1812-z

[4] Grice EA, Segre JA. The skin microbiome [published correction appears in Nat Rev Microbiol. 2011 Aug;9(8):626]. Nat Rev Microbiol. 2011;9(4):244-253. doi:10.1038/nrmicro2537

[5] Scales BS, Huffnagle GB (2013): The Microbiome in Wound Repair and Tissue Fibrosis, J Pathol. 2013 January ; 229(2): 323–331. doi:10.1002/path.4118.

[6] Fuentes, I., Guttmann-Gruber, C., Tockner, B. et al. Cells from discarded dressings differentiate chronic from acute wounds in patients with Epidermolysis Bullosa. Sci Rep 10, 15064 (2020). https://doi.org/10.1038/s41598-020-71794-1

[7] Martinotti S, Ranzato E. Propolis: a new frontier for wound healing?. Burns Trauma. 2015;3:9. Published 2015 Jul 22. doi:10.1186/s41038-015-0010-z

[8] Bankova V, Popova M, Trusheva B. Propolis volatile compounds: chemical diversity and biological activity: a review. Chem Cent J. 2014;8:28. Published 2014 May 2. doi:10.1186/1752-153X-8-28

[9] Grice EA, Segre JA. The skin microbiome [published correction appears in Nat Rev Microbiol. 2011 Aug;9(8):626]. Nat Rev Microbiol. 2011;9(4):244-253. doi:10.1038/nrmicro2537

[10] Chen YE, Fischbach MA, Belkaid Y. Skin microbiota-host interactions [published correction appears in Nature. 2018 Mar 21;555(7697):543]. Nature. 2018;553(7689):427-436. doi:10.1038/nature25177

[11] SanMiguel, A., & Grice, E. A. (2015). Interactions between host factors and the skin microbiome. Cellular and molecular life sciences : CMLS, 72(8), 1499–1515. https://doi.org/10.1007/s00018-014-1812-z

[12] O’Meara S, Al-Kurdi D, Ologun Y, et al. Antibiotics and antiseptics for venous leg ulcers.

Cochrane Database Syst Rev. 2010:CD003557.

[13] Ring J. (2020). The skin in the era of coronavirus pandemic. Journal of the European Academy of Dermatology and Venereology : JEADV, 34(7), 1384–1385. https://doi.org/10.1111/jdv.16718

[14] Xue, X., Mi, Z., Wang, Z., Pang, Z., Liu, H., & Zhang, F. (2020). High Expression of ACE2 on Keratinocytes Reveals Skin as a Potential Target for SARS-CoV-2. The Journal of investigative dermatology, S0022-202X(20)31602-X. Advance online publication. https://doi.org/10.1016/j.jid.2020.05.087

[15] Kumpitsch C, Koskinen K, Schöpf V, Moissl-Eichinger C. The microbiome of the upper respiratory tract in health and disease. BMC Biol. 2019;17(1):87. Published 2019 Nov 7. doi:10.1186/s12915-019-0703-z

[16] Perniss A, Liu S, Boonen B, et al. Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides. Immunity. 2020;52(4):683-699.e11. doi:10.1016/j.immuni.2020.03.005

[17] Is Nasal Irrigation Beneficial in COVID-19? – Medscape – Jul 29, 2020.

https://www.medscape.com/viewarticle/934807?nlid=136745_4663&src=WNL_mdplsnews_200807_mscpedit_fmed&uac=290363HR&spon=34&impID=2495938&faf=1

[18] Is Nasal Irrigation Beneficial in COVID-19? – Medscape – Jul 29, 2020.

https://www.medscape.com/viewarticle/934807?nlid=136745_4663&src=WNL_mdplsnews_200807_mscpedit_fmed&uac=290363HR&spon=34&impID=2495938&faf=1

[19] Zipperer A, Laux M  et al. (2016). Human commensals producing a novel antibiotic impair pathogen colonization. Nature. 535. 511-516. 10.1038/nature18634.

[20] Dimitri-Pinheiro S, Soares R, Barata P. The Microbiome of the Nose-Friend or Foe?. Allergy Rhinol (Providence). 2020;11:2152656720911605. Published 2020 Mar 13. doi:10.1177/2152656720911605

[21] Tsang TK, Lee KH, Foxman B, et al. Association between the respiratory microbiome and susceptibility to influenza virus infection [published online ahead of print, 2019 Sep 28]. Clin Infect Dis. 2019;ciz968. doi:10.1093/cid/ciz968

[22] Zhou Y, Jackson D, Bacharier LB, et al. The upper-airway microbiota and loss of asthma control among asthmatic children. Nat Commun. 2019;10(1):5714. Published 2019 Dec 16. doi:10.1038/s41467-019-13698-x

Fazlollahi M, Lee TD, Andrade J, et al. The nasal microbiome in asthma. J Allergy Clin Immunol. 2018;142(3):834-843.e2. doi:10.1016/j.jaci.2018.02.020

[23] Probiotics Reduce Allergic Rhinitis in Children and Adults – Medscape – Jun 18, 2020.

https://www.medscape.com/viewarticle/932591?src=wnl_edit_tpal&uac=290363HR&impID=2426938&faf=1#vp_2

[24] Keir J. Why do we have paranasal sinuses?. J Laryngol Otol. 2009;123(1):4-8. doi:10.1017/S0022215108003976

[25] Eccles RB. The nasal cycle in respiratory defence. Acta Otorhinolaryngol Belg. 2000;54(3):281-286.

[26] Pendolino AF, Lund VJ, Ennio Nardello E, Ottaviano G (2018): The nasal cycle: a comprehensive review, Rhinology Online, Vol 1: 67-76, 2018, http://doi.org/10.4193/RHINOL/18.021

[27] Wu A, Mihaylova VT et al. (2020):  Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study, The Lancet Microbe, Published: September 04, 2020, DOI:https://doi.org/10.1016/S2666-5247(20)30114-2

[28]  van den Aardweg M T A, Boonacker C W B, Rovers M M, Hoes A W, Schilder A G M. Effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections: open randomised controlled trial BMJ 2011; 343 :d5154

[29] Do Not Use Decongestants for Colds in Children Younger Than Age 6 – Medscape – Oct 12, 2018.

https://www.medscape.com/viewarticle/903384#vp_1

[30] Is Nasal Irrigation Beneficial in COVID-19? – Medscape – Jul 29, 2020.

https://www.medscape.com/viewarticle/934807

[31] Khan MM, Parab SR, Paranjape M. Repurposing 0.5% povidone iodine solution in otorhinolaryngology practice in Covid 19 pandemic [published online ahead of print, 2020 Jun 18]. Am J Otolaryngol. 2020;41(5):102618. doi:10.1016/j.amjoto.2020.102618

[32] Han YW, Wang X. Mobile microbiome: oral bacteria in extra-oral infections and inflammation. J Dent Res. 2013;92(6):485-491. doi:10.1177/0022034513487559

[33] Marsh PD. In Sickness and in Health-What Does the Oral Microbiome Mean to Us? An Ecological Perspective. Adv Dent Res. 2018;29(1):60-65. doi:10.1177/0022034517735295

[34] Ganesan SM, Dabdoub SM, Nagaraja HN, et al. Adverse effects of electronic cigarettes on the disease-naive oral microbiome. Sci Adv. 2020;6(22):eaaz0108. Published online 2020 May 27. https://advances.sciencemag.org/content/6/22/eaaz0108.full. Accessed May 28, 2020.

[35] Costalonga M, Herzberg MC. The oral microbiome and the immunobiology of periodontal disease and caries. Immunol Lett. 2014;162(2 Pt A):22-38. doi:10.1016/j.imlet.2014.08.017

[36] Meister TL, Brüggemann Y, Todt D, et al. Virucidal Efficacy of Different Oral Rinses Against Severe Acute Respiratory Syndrome Coronavirus 2. J Infect Dis. 2020;222(8):1289-1292. doi:10.1093/infdis/jiaa471

[37] Can Mouthwash Douse the Spread of COVID-19? – Medscape – Jun 12, 2020.

https://www.medscape.com/viewarticle/932214?src=mkm_ret_200625_mscpmrk_eumonthly_int&uac=290363HR&impID=2432534&faf=1

[38] Meister TL, Brüggemann Y, Todt D, et al. Virucidal efficacy of different oral rinses against SARS-CoV-2 [published online ahead of print, 2020 Jul 29]. J Infect Dis. 2020;jiaa471. doi:10.1093/infdis/jiaa471

[39] Sampson V, Kamona N, Sampson A. Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections?. Br Dent J. 2020;228(12):971-975. doi:10.1038/s41415-020-1747-8

[40] Mathieu, E., Escribano-Vazquez, U., Descamps, D., Cherbuy, C., Langella, P., Riffault, S., Remot, A., & Thomas, M. (2018). Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma. Frontiers in physiology, 9, 1168. https://doi.org/10.3389/fphys.2018.01168

[41] Mathieu, E., Escribano-Vazquez, U., Descamps, D., Cherbuy, C., Langella, P., Riffault, S., Remot, A., & Thomas, M. (2018). Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma. Frontiers in physiology, 9, 1168. https://doi.org/10.3389/fphys.2018.01168

[42] Lang JE. The impact of exercise on asthma. Curr Opin Allergy Clin Immunol. 2019;19(2):118-125. doi:10.1097/ACI.0000000000000510

Francisco CO, Bhatawadekar SA, Babineau J, Reid WD, Yadollahi A. Effects of physical exercise training on nocturnal symptoms in asthma: Systematic review. PLoS One. 2018;13(10):e0204953. Published 2018 Oct 22. doi:10.1371/journal.pone.0204953

[43] Barcik, W., Boutin, R., Sokolowska, M., & Finlay, B. B. (2020). The Role of Lung and Gut Microbiota in the Pathology of Asthma. Immunity, 52(2), 241–255. https://doi.org/10.1016/j.immuni.2020.01.007

[44] Kaur G, Lungarella G, Rahman I. SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping. J Inflamm (Lond). 2020;17:21. Published 2020 Jun 10. doi:10.1186/s12950-020-00250-8

[45] Gaiha SM, Cheng J, Halpern-Felsher B (2020): Association Between Youth Smoking, Electronic Cigarette Use, and Coronavirus Disease 2019. Journal of Adolescent Health, 2020; DOI: 10.1016/j.jadohealth.2020.07.002