In the face of pandemic we are looking for solutions that will help us to fight with the pathogen. Scientists observe course of infection among different patients to find out what decides of gentle or severe progression of COVID-19. How to identify high risk group? Is only age decisive for the severe course of COVID-19? And if so, how to explain the phenomenon of recovering 100 year olds?

At the beginning it must be mentioned that direct cause of death from COVID-19 I often not the infection itself, but suicidal attack of immune system on infected tissues. Situation like this is known as cytokine storm and is caused by dysregulation of immune response. Knowing this, we can conclude that the proper regulatory mechanisms and the good condition of the immune system can determine whether we can get to the infection without much damage.

One of the hypothesis taken under consideration right now is impact of microbiom on course of infection with novel coronavirus. Where did this idea come from? Everything started from Chinese publication indicating incorrect microbiom status among patients with severe course of COVID-19.

Another argument, convincing scientists to take a closer look on the situation in the gut , is increasing number of publications showing presence of gastrointestinal symptoms among patients with COVID-19 [1]. At the beginning indicated percentage of ill with gastrointestinal symptoms oscillated around 5-10% but later along with development of events it shown 50-60%. Turned out that intestinal symptoms precede development of respiratory symptoms and predispose to more severe infection [2,3].

Later, thanks to a team of researchers from the Netherlands, we learned that the receptor for COVID-19 (ACE-2) is present in the intestines and that the virus is able to actively replicate in the intestinal mucosa [4].

Turned out also, that intestinal microbiom can have an impact on development of cytokine storm [5]. Metabolites of intestinal bacteria have an effect on production of proinflammatory cytokines. Microbiom can sometimes increase amount of acute phase proteins and interferon signalling in lung cells, to protect organism against infection. Unfortunately sometimes in course of CIVID-19 immunological response gets out of control. Excessive release of proinflammatory cytokines leads to hyperinflammation and ultimately to acute respiratory distress syndrome (SARDS) and multiorgan failure [6].

Many experimental and clinical observations suggest that intestinal microbiom is crucial in pathogenesis of sepsis and SARDS [7]. t has also been shown that the intestinal microbiome affects lung health through a significant interaction between the microbiome and the lungs, which is referred to as the “gut-lung axis” [8].

Hypothesis based on importance of microbiom could partially explain, why elderly are more prone to develop acute respiratory failure and lose their lives due to coronavirus infection. Older people experience significant changes in the microbiome profile, which may predispose to an increased inflammatory response and worse tolerance of viral infections. It would also explain why some seniors cope well with infection, especially if they are in good health despite their age.

Studies show that longevous and healthy people, heathy centerians, have a microbiome similar in composition to the healthy microbiome of 30-year-olds [9]. Their microbiome “does not age” as researchers suppose due to a healthy lifestyle and a proper diet. There is also a concept of age-related inflammation caused by microbiome disorders. This phenomenon was first observed in an animal model study where a young mouse was transplanted with an old mouse microbiome. As a result, young mice developed inflammaging and increased TNF-alpha production [10].

We can also find examples of the protective effect of probiotic bacteria on the development of a viral infection. A meta-analysis study of 1244 publications showed a significant effect of probiotic supplementation on shortening the duration and relief of symptoms during rotavirus infection [11]. A healthy intestinal microbiome can also produce substances protecting us against the virus. One study in an animal model concerned influenza infection. It has been found that LPS from commensal microbiota can bind and destabilize influenza virions, thus reducing overall stability of the virus [12].

It may turn out that healthy lifestyle, correct diet and fibre intake can have impact not only on our weight and prevention of diet related illnesses but also our immunity and longevity. Keeping the microbiome in good condition can pay off not only not only in times of pandemics.

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Bibliography:

1. Jin, X., et al. (2020). Epidemiological, clinical and virological 847 characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with 848 gastrointestinal symptoms. Gut

2. Lin, L., et al. (2020). Gastrointestinal symptoms of 95 cases with SARS-CoV-2 863 infection. Gut.

3. Ng, S.C., and Tilg, H. (2020). COVID-19 and the gastrointestinal tract: more than 881 meets the eye. Gut.

4. Science 10.1126/science.abc1669 (2020). SARS-CoV-2 productively infects human gut enterocytes Mart M. Lamers, Joep Beumer, Jelte van der Vaart, Kèvin Knoops

5. Microbiota-dependent signals are required to sustain TLR-mediated immune responses. Weaver LK, Minichino D, Biswas C, Chu N, Lee JJ, Bittinger K, Albeituni S, Nichols KE, Behrens EM. JCI Insight. 2019 Jan 10;4(1)

6. 5. Front Immunol. 2019 Jul 4;10:1551. doi: 10.3389/fimmu.2019.01551. eCollection 2019,The Commensal Microbiota and Viral Infection: A Comprehensive Review. Li N1, Ma WT1, Pang M1, Fan QL2, Hua JL1

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8. S. Keely, N.J. Talley, P.M. Hansbro Pulmonary-intestinal cross-talk in mucosal inflammatory disease Mucosal Immunol., 5 (1) (2012), pp. 7-18

9. Bian G, Gloor GB, Gong A, et al. The gut microbiota of healthy aged Chinese is similar to that of the healthy young. mSphere. 2017; 2(5). doi: 10.1128/mSphere.00327-17.

10. Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice, Front. Immunol., 02 November 2017 Floris Fransen, Adriaan A. van Beek, Theo Borghuis

11. Efficacy of probiotic use in acute rotavirus diarrhea in children: A systematic review and meta-analysis. Ahmadi E, Alizadeh-Navaei R, Rezai MS. Caspian J Intern Med. 2015 Fall;6(4):187-95

12. Bandoro C, Runstadler JA. Bacterial lipopolysaccharide destabilizes influenza viruses. mSphere. (2017) 2:17