Is there a rationale for endotoxin removal in severely ill COVID-19 patients? As a matter of fact, 90% of patients with severe pulmonary forms of COVID-19 have increased endotoxin levels and the level of endotoxin is directly related to the severity of COVID-19. 1,2 Also, these patients are at high risk of sepsis. 3
Endotoxin triggers cytokine storms
The spike protein in SARS-CoV-2 has been shown to bind to endotoxin, starting the inflammatory signalling and dysregulated immune response. 4 Endotoxin is one of the most potent bacterial inducers of cytokines and can induce a cytokine storm through binding to Toll-like receptor 4 (TLR4). 5,6,7,8
High risk and prevalence of bacterial infections
Dysregulation of the immune system may be associated with a high risk of developing a secondary bacterial infection. Studies show that up to 60% of COVID-19 patients in the ICU have secondary bacterial infections – most commonly respiratory infections from gram-negative bacteria. 9
COVID-19 patients with pulmonary superinfections require longer ICU-treatments 10 and are at higher risk of ventilator-associated pneumonia (VAP) 11 – in fact, it is the most frequent hospital acquired infection in these patients, and it is often caused by gram-negative bacteria. Furthermore, VAP has been demonstrated to be the most frequent hospital infection associated with septic shock. 12
In the absence of a bacterial infection, antibiotic treatment can cause release of endotoxin, triggering endotoxemia and over-production of pro-inflammatory cytokines – an antibiotic-induced inflammatory storm. 13
Translocation of bacteria from the gut
Endotoxin in COVID-19 does not originate from the virus itself but is thought to be released from gram-negative bacteria in the gut, due to inadequate blood flow. 14,15,16,17 The gut barrier dysfunction that allows endotoxin to leak out from the gut into the blood, can potentially cause sepsis and multiple organ failure. 18 Also, it can travel to the lungs and affect the immune response as well as the lung microbial composition. 19
It is argued that comorbidities of COVID-19 such as obesity, type 2 diabetes, cardiovascular diseases, and old age of patients – comorbidities in which increased levels of endotoxin are found – are connected via viral–bacterial interactions, initiated by translocation of bacterial products such as endotoxin from the gut into circulation. 20 In fact, translocation of endotoxin could play a larger role than previously thought in severely ill COVID-19 patients. 21
Complement activation increases endotoxin levels
The use of mechanical and hemodynamic support heightens the immune response of the patient. Being on ECMO- and/or a CRRT machine, the patient may have an inflammatory response to extracorporeal circulation (complement activation) resulting in increased endotoxin levels. 22,23,24,25
Endotoxin removal in COVID-19 – conclusion
Extracorporeal techniques have a possible role in “restoring a balanced immune response by eliminating/deactivating inflammatory mediators”. 26 Binding and clearing endotoxins from circulation could be an appropriate intervention in the fight against COVID-19.
Studies have shown that endotoxin adsorbtion results in clinical improvement in severe COVID-19 patients with elevated endotoxin levels (measured by EAA, Endotoxin Activity Assay). 27 The Alteco LPS Adsorber removes endotoxin (lipopolysaccharide, LPS) from the patient’s blood as it passes through the device. Based on the significance of endotoxin in COVID-19, the Alteco LPS Adsorber may be of use in COVID-19 patients suspected to have gram-negative bacterial infection, signs of inflammatory response, endotoxemia or sepsis. 28 The removal of endotoxin turns down the exacerbated immune response, helping to stabilize the patient’s hemodynamic parameters. 29
Webinar: endotoxemia in COVID-19
Bacterial translocation from GI-tract might complicate severe COVID-19. Bacterial products might be another possible contributor to the cytokine storm.
Jakub Smiechowicz, Barbara Adamik
Department of Anesthesiology and Intensive Therapy
Wroclaw Medical University, Poland
Inside the Alteco LPS Adsorber, a tailor-made synthetic peptide binds to Lipid A; the toxic part of endotoxin. By adsorbing harmful levels of endotoxin from the patient’s bloodstream during extracorporeal treatment in the ICU, the Alteco LPS Adsorber breaks the chain of immune system over-reactions that can spiral into septic shock. This can turn the course of sepsis and stabilize the patient’s hemodynamic parameters in 2 hours. 29
Take endotoxin out of the picture
View our product animation to learn more about endotoxin removal and the Alteco LPS Adsorber.
Early treatment start
High levels of endotoxin activity are associated with organ failure and death. 3 Therefore, starting treatment early is important. Use the Alteco LPS Adsorber to counteract the critical and life-threatening part of the sepsis process. Remove endotoxin from the bloodstream to regain control over the systemic failure and stabilize the patient in the acute situation.
What role does LPS play in the gut-lung axis dysbiosis in COVID-19 patients? …”the direct invasion of the intestine by SARS-CoV-2 leads to increased intestinal permeability, allowing LPS produced by harmful bacteria to invade the body and stimulate the production of certain cytokines”…
“…all ICU staff and physicians should be familiar with the concept of hemoperfusion in management of critically ill patients. So, hemoperfusion (early application) combined with appropriate antiviral therapies and supportive therapy may be considered as an adjunctive treatment for critically ill COVID-19 patients.”
Secondary infections – most commonly gram-negative urinary tract infections and blood stream infections - complicate as much as 10% of COVID-19 patients in the hospital, increasing the need for oxygen, ICU care and almost doubling the length of stay.
Did you know that COVID-19 patients are 3.5 times more likely to develop a hospital onset bloodstream infection? Many of these infections originate from gram-negative bacteria (escherichia coli, pseudomonas aeruginosa, klebisella pneumoniae).
Did you know that endotoxemia can be present in critically ill patients with COVID-19, independent of superimposed gram-negative infections? A leaky gut barrier might contribute to endotoxin translocation. Study observes elevated endotoxin activity in 75% of critically ill patients with COVID-19 – and higher acute kidney injury rates.
The vicious cycle: SARS-CoV-2 spike protein binds to lipopolysaccharide (LPS) -> boosting pro-inflammatory activity -> cytokine storm -> intestinal damage -> impaired barrier function -> translocation of gram-negative bacteria, more endotoxin in the blood stream -> escalating inflammation.