Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 7; p. 1103
• Main Authors: Saithong, Supichcha, Worasilchai, Navaporn, Saisorn, Wilasinee, Udompornpitak, Kanyarat, Bhunyakarnjanarat, Thansita, Chindamporn, Ariya, Tovichayathamrong, Punyot, Torvorapanit, Pattama, Chiewchengchol, Direkrit, Chancharoenthana, Wiwat, Leelahavanichkul, Asada
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.03.2022; MDPI
• Subjects: Arginine deiminase; Bacteria; Bacterial infections; beta-Glucans; blood bacteriome; Coronaviruses; COVID-19; Creatinine; Cytokine storm; Cytokines; Deoxyribonucleic acid; DNA; Elastase; endotoxemia; Enzymes; Extracellular Traps; Fungi; glucanemia; gut barrier defect; Histones; Hospitals; Humans; Hypoxia; Infections; Interleukin 6; Interleukin 8; Leukocytes (neutrophilic); Lipopolysaccharides; Lipopolysaccharides - pharmacology; Morphology; NETs; Neutrophilia; Neutrophils; NF-κB protein; Pathogens; Patients; Peroxidase; Pneumonia; Polymerase chain reaction; Protein-arginine deiminase; Reactive oxygen species; Respiratory syncytial virus; Respiratory tract; SARS-CoV-2; Sepsis; Severe acute respiratory syndrome coronavirus 2; Viral infections; United Kingdom > UK; United States > US; Switzerland; COVID-19; blood bacteriome; glucanemia; NETs; gut barrier defect; endotoxemia
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11071103

Due to limited data on the link between gut barrier defects (leaky gut) and neutrophil extracellular traps (NETs) in coronavirus disease 2019 (COVID-19), blood samples of COVID-19 cases-mild (upper respiratory tract symptoms without pneumonia; = 27), moderate (pneumonia without hypoxia; = 28), and severe (pneumonia with hypoxia; = 20)-versus healthy control ( = 15) were evaluated, together with in vitro experiments. Accordingly, neutrophil counts, serum cytokines (IL-6 and IL-8), lipopolysaccharide (LPS), bacteria-free DNA, and NETs parameters (fluorescent-stained nuclear morphology, dsDNA, neutrophil elastase, histone-DNA complex, and myeloperoxidase-DNA complex) were found to differentiate COVID-19 severity, whereas serum (1→3)-β-D-glucan (BG) was different between the control and COVID-19 cases. Despite non-detectable bacteria-free DNA in the blood of healthy volunteers, using blood bacteriome analysis, proteobacterial DNA was similarly predominant in both control and COVID-19 cases (all severities). In parallel, only COVID-19 samples from moderate and severe cases, but not mild cases, were activated in vitro NETs, as determined by supernatant dsDNA, , and nuclear morphology. With neutrophil experiments, LPS plus BG (LPS + BG) more prominently induced NETs, cytokines, , and reactive oxygen species, when compared with the activation by each molecule alone. In conclusion, pathogen molecules (LPS and BG) from gut translocation along with neutrophilia and cytokinemia in COVID-19-activated, NETs-induced hyperinflammation.