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. 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).
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.
COVID-19 patients with pulmonary superinfections require longer ICU-treatments and are at higher risk of ventilator-associated pneumonia (VAP) – 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.
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.
Translocation of bacteria from the gutEndotoxin 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. The gut barrier dysfunction that allows endotoxin to leak out from the gut into the blood, can potentially cause sepsis and multiple organ failure. Also, it can travel to the lungs and affect the immune response as well as the lung microbial composition.
Endotoxin removal in COVID-19 – conclusion
Extracorporeal techniques have a possible role in “restoring a balanced immune response by eliminating/deactivating inflammatory mediators”. 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). 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. The removal of endotoxin turns down the exacerbated immune response, helping to stabilize the patient’s hemodynamic parameters.