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Markers of Fungal Translocation Are Elevated During Post-Acute Sequelae of SARS-CoV-2 Infection and Induce NF-κB Triggered Inflammation [article]

Leila B. Giron, Michael Peluso, Jianyi Ding, Grace Kenny, Netanel F Zilberstein, Jane Koshy, Kai Ying Hong, Heather Rasmussen, Greg Miller, Faraz Bishehsari, Robert A. Balk, James N. Moy (+17 others)
2022 bioRxiv   pre-print

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https://web.archive.org/web/20220423111924/https://www.biorxiv.org/content/biorxiv/early/2022/04/13/2022.04.12.488051.full.pdf

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Long COVID, a type of Post-Acute Sequelae of SARS CoV-2 infection (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the pathophysiological mechanisms that drive this inflammation remain unknown. Inflammation during acute Coronavirus Disease 2019 (COVID-19) could be exacerbated by microbial translocation (from the gut and/or lung) to the blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We found
more » ... er levels of fungal translocation - measured as beta-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared to those without PASC or SARS-CoV-2 negative controls. The higher beta-glucan correlated with higher levels of markers of inflammation and elevated levels of host metabolites involved in activating N-Methyl-D-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neuro-toxic properties. Mechanistically, beta-glucan can directly induce inflammation by binding to myeloid cells (via the Dectin-1 receptor) and activating Syk/NF-kB signaling. Using an in vitro Dectin-1/NF-kB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-kB signaling compared to plasma from SARS-CoV-2 negative controls. This higher NF-kB signaling was abrogated by the Syk inhibitor Piceatannol. These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.
doi:10.1101/2022.04.12.488051 fatcat:ky77drjblfbcxat6rmbcnp2uqa
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Leila B. Giron, Michael Peluso, Jianyi Ding, Grace Kenny, Netanel F Zilberstein, Jane Koshy, Kai Ying Hong, Heather Rasmussen, Greg 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. Petropoulos, J. Daniel Kelly, Haimanot Wasse, Jeffrey N. Martin, Qin Liu, Ali Keshavarzian, Alan Landay, Steven G. Deeks, Timothy J. Henrich, Mohamed Abdel-Mohsen. "Markers of Fungal Translocation Are Elevated During Post-Acute Sequelae of SARS-CoV-2 Infection and Induce NF-κB Triggered Inflammation." bioRxiv (2022)