Endotoxin removal in COVID-19

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

View our product animation to learn more about endotoxin removal and the Alteco LPS Adsorber.

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.