ResearchIn-Press PreviewCOVID-19Virology
Open Access | 10.1172/jci.insight.160989
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Giron, L.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Peluso, M.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Kenny, G.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Miller, G.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Hoh, R.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Goldman, A.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Tang, H.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Yee, B.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Wasse, H.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Liu, Q.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Deeks, S.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Henrich, T.
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1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America
2The University of California, San Francisco, San Francisco, United States of America
3Department of Infectious Diseases, University College Dublin, Dublin, Ireland
4Department of Internal Medicine, Rush University, Chicago, United States of America
5Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, United States of America
6Department of Psychology, Northwestern University, Chicago, United States of America
7Department of Medicine, The University of California, San Francisco, San Francisco, United States of America
8Monogram Biosciences, South San Francisco, United States of America
9Oncology Group, Monogram Biosciences, South San Francisco, United States of America
10Department of Digestive Diseases, Rush University, Chicago, United States of America
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Published June 21, 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 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 to 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 neuro-toxic 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 to 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.