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Severe Covid-19 outcomes and inducible endotoxemia

[mercedesman]

Preexisting and inducible endotoxemia as crucial contributors to the severity of COVID-19 outcomes

German and U of Texas Authors

At a first glance, the correlations seem odd, since these comorbidities are not simply connected to a single specific disorder and are not even COVID-19 specific—most of them were reported for other viral infections as well, including the Middle East Respiratory Syndrome (MERS) and H1N1 (swine flu). However, recently, we have argued that all of these comorbidities have something in common and are connected via viral–bacterial interactions, initiated by translocation of bacterial products, such as lipopolysaccharide (LPS), from the gut into circulation. Indeed, increased plasma levels of LPS and LPS-binding protein (LBP) are found in obesity and diabetes, and gut dysbiosis is involved in the pathogenesis of insulin resistance. 

Whereas gut microbiota may determine the predisposition of healthy individuals to COVID-19 [6], direct virus–LPS interactions were not considered as a main pathophysiological driver inducing these effects. However, viruses can bind to bacteria or directly to free LPS, thereby enhancing their attachment to ACE2 receptors on the surface of host cells. Such interactions can dramatically increase the viral infectivity and promote the development of hypercytokinemia...

Several clinical reports demonstrate significantly increased levels of endotoxins in the plasma of severely affected COVID-19 patients...

Whereas preexisting endotoxemia in groups at risk for COVID-19 has been intensely studied, the overall influence and degree of induced endotoxemia, especially in connection to SARS-CoV-2, has not yet been properly investigated. The main question here to be addressed is whether SARS-CoV-2 can effectively increase the permeability of the intestinal barrier for bacterial products....

COVID-19 in its severe forms is unquestionably a systemic disease. Whereas the main signs of severity in this disease are associated with the development of systemic hypercytokinemia and pulmonary complications, we suspect that more severe outcomes of COVID-19 must be connected with a baseline predisposition toward a compromised state of the intestine (preexisting endotoxemia). Upon infection, a dramatic worsening of this state ensues, primarily through a SARS-CoV-2-induced ACE2 deficiency leading to induced endotoxemia and a deteriorated endotoxin tolerance. The unique role that preexisting endotoxemia may play in the development of severe COVID-19 leads us to postulate that standard measurements of LPS and LBP in plasma, immediately upon receiving a positive COVID-19 test, could be a valuable diagnostic help to identify individuals at risk of severe outcomes. This suggested that pathophysiology can also direct us toward appropriate choices to intervene in this process, particularly toward approaches that aim to bind and clear endotoxins from circulation. 


https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009306


MM


PS  I wonder how or what could be used to measure "LPS in plasma", and identify those at risk of severe outcomes, as a standard protocol for Covid-19 patients ?