Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

• DOI: 10.1172/jci.insight.160989
• Publication Date: 2022-06-21T16:00:22Z
• Authors: Leila B. Giron; Michael J. Peluso; Jianyi Ding; Grace Kenny; Netanel F. Zilber...; Jane Koshy; Kai Ying Hong; Heather Rasmussen; Gregory E. Miller; Faraz Bishehsari; Robert A. Balk; James N. Moy; Rebecca Hoh; Scott Lu; Aaron R. Goldman; Hsin-Yao Tang; Brandon C. Yee; Ahmed Chenna; John W. Winslow; Christos J. Petro...; J. Daniel Kelly; Haimanot Wasse; Jeffrey N. Martin; Qin Liu; Ali Keshavarzian; Alan Landay; Steven G. Deeks; Timothy J. Henrich; Mohamed Abdel-Mohsen
• Keywords: and Biochemical Nutrition; beta-Glucans; Other Nutrition; 610; Vaccine Related; Post-Acute COVID-19 Syndrome; Genetic; Biodefense; Lectins; Virology; 2.1 Biological and endogenous factors; Syk Kinase; Humans; Lectins, C-Type; Aetiology; Lung; Tight junctions; Nutrition; Inflammation; C-Type; SARS-CoV-2; Prevention; Inflammatory and immune system; R; NF-kappa B; Molecular; COVID-19; Pneumonia; 3. Good health; Infectious Diseases; Emerging Infectious Diseases; Good Health and Well Being; Medicine; Infection; Corrigendum; Human and Clinical Nutrition; Research Article; Signal Transduction

Long COVID, a type of post-acute sequelae SARS-CoV-2 (PASC), has been associated with sustained elevated levels immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from gut and/or lung) to blood. Whether contributes PASC is We did not observe significant elevation in plasma markers bacterial PASC. we observed higher fungal - measured as β-glucan, cell wall polysaccharide individuals experiencing compared those without or SARS-CoV-2-negative controls. The β-glucan correlated host metabolites involved activating N-methyl-d-aspartate receptors (such within tryptophan catabolism pathway) established neurotoxic properties. Mechanistically, can directly induce binding myeloid cells (via Dectin-1) Syk/NF-κB signaling. Using Dectin-1/NF-κB reporter model, found from induced NF-κB signaling negative This was abrogated piceatannol (Syk inhibitor). These data suggest potential targetable mechanism linking