Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients

Abstract

Mucosal barrier alterations may play a role in the pathogenesis of several diseases, including COVID-19. In this study we evaluate the association between bacterial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR positive patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, lipopolysaccharide (LPS) concentrations and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-β1, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, the coexistence of increased microbial translocation and hyperinflammation in patients with severe COVID-19 may lead to higher monocyte activation, which may be associated with worsening outcomes, such as death.

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic

“…Multiple-fold increases in CCL5 expression in severe COVID-19 patients compared to healthy individuals are well documented ( 311 , 312 , 315 , 324 ). Additionally, there was a significant increase in CCL5 expression in non-surviving COVID-19 patients compared to severe, mild and healthy groups ( 313 ). Furthermore, high levels of CCL5 cause liver disorders and acute kidney injury (AKI) in COVID-19 patients ( 314 , 318 , 325 ).…”

“…In this module, we also identified several hub-high traffic genes that were crucial in regulating the host immune response during COVID-19. These hub-high traffic genes included CDKN2A (308,309), OASL (282,310), CCL5 (311)(312)(313)(314)(315)(316), KIF2C (4), and CD8A (317). Among them, the CCL5 hub-high traffic gene has the most important role in regulating the inflammatory response and the host immune system; however, its excessive expression can amplify inflammatory responses toward immunopathology (e.g., cytokine storm) (311,314).…”

Alterations in CD39/CD73 axis of T cells associated with COVID‐19 severity

“…The data were processed using LabSolutions software (Shimadzu). In addition, LPS concentration was determined by quantification of 3‐hydroxytetradecanoic acid as described by Teixeira et al ( 2021 ).…”

Unhealthy Dieting During the COVID-19 Pandemic: An Opinion Regarding the Harmful Effects on Brain Health

“…This constant cycle (higher dietary fat intake and blood LPS) favors the development of chronic metabolic disruptions, like insulin resistance ( 26 ). Recently, Teixeira et al ( 27 ) demonstrated an increased microbial translocation and hyper inflammation in patients with severe COVID-19, provoking higher monocyte activation, which may be associated with worsening outcomes, including death.…”