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COVID-19: Gut barrier functions and lung injury

According to a retrospective study 86,7% of COVID-19 patients have gastrointestinal symptoms. (1) With the help of angiotensin converting enzyme-2 (ACE2) protein the virus has access to the human cells. It is abundantly present in the gastrointestinal tract and mostly in the epithelia of the small intestine and lung and in arterial and venous endothelial cells. (2) The barrier tissues of the small intestine and lung can be injured in two ways: the virus can directly attack the tissues and injure barrier functions or the over activated immune cells by cytokine storm can harm these tissues. Infected people have a worse disease course if their gastrointestinal injury is more severe. They have higher septic shock incidence, and higher hospital mortality. This may be also explained by secondary bacterial infections. According to one of the largest retrospective study 50% of the fatal cases had secondary bacterial infection acquired in the hospital. (3) The secondary bacterial infections and antibiotic resistance may be caused by the injury of gut barrier, tight junction functions that may be also exacerbated by mechanical ventilation caused lung injury and increased cytokine storm. Advanced age is also a risk factor for the injury of the tight junctions of the gut and bacterial translocation to the lung. (4) The bacterial infections due to the impaired tight junction functions are antibiotic resistant as this can be observed in stroke patients. (5) The antibiotic treatment is also problematic because in experimental settings prophylactic antibiotic use increases the damages to the lung, enhances the inflammatory cytokine (Il-6), caused by mechanic ventilation. This is probably due to microbiota depletion. (6) Inflammation impairs the heart rate variability (HRV), the cholinergic anti-inflammatory pathway. (7) The activation of the vagus nerve, the cholinergic anti-inflammatory pathway may reduce the injury of the tight junctions and gut barrier. (8) Proinsulin C-peptide can activate the vagus nerve and combined with zinc supplementation may be more effective than antibiotics in polymicrobial sepsis, it may decrease infection and mortality and increase HRV. (9)(10) (11) Parasympathetic stimulation via the vagus nerve may prevent also systemic organ dysfunction by abrogating gut injury. (12) Central (intranasal) C-peptide administration is an easy way to achieve most of the beneficial effects described.


(1) https://www.medrxiv.org/content/10.1101/2020.03.25.20043570v1.full.pdf
(2) https://pubmed.ncbi.nlm.nih.gov/15141377/
(3)  https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext
(4) https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12980
(5) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107889/
(6) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206919/
(7) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476948/
(8) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251593/
(9) https://pubmed.ncbi.nlm.nih.gov/16005542/
(10) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968544/
(11) https://pubmed.ncbi.nlm.nih.gov/8781764/
(12) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547655/

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