Published September 22, 2022 - More info
Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of 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 the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation — measured as β-glucan, a fungal cell wall polysaccharide — in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2–negative controls. The higher β-glucan correlated with higher 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 neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.
Leila B. Giron, Michael J. Peluso, Jianyi Ding, Grace Kenny, Netanel F. Zilberstein, 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. Petropoulos, J. Daniel Kelly, Haimanot Wasse, Jeffrey N. Martin, Qin Liu, Ali Keshavarzian, Alan Landay, Steven G. Deeks, Timothy J. Henrich, Mohamed Abdel-Mohsen
Original citation: JCI Insight. 2022;7(15):e160989. https://doi.org/10.1172/jci.insight.160989
Citation for this corrigendum: JCI Insight. 2022;7(18):e164813. https://doi.org/10.1172/jci.insight.164813
For clarity, the authors have updated Table 1 so that the percentages of each variable in the UCSF LIINC cohort reflect percentages within each group (No PASC and PASC). The correct Table 1 is below. The online HTML and PDF versions of the manuscript have been updated to reflect these changes.
Demographic and clinical characteristics of study cohorts
The authors regret the errors.