Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium.

التفاصيل البيبلوغرافية
العنوان: Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium.
المؤلفون: Ziegler CGK; Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA.; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Owings AH; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Miao VN; Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Navia AW; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA., Tang Y; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA., Bromley JD; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Microbiology, Massachusetts Institute of Technology, Cambridge, MA, USA., Lotfy P; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA., Sloan M; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Laird H; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS, USA., Williams HB; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS, USA., George M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Drake RS; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Pride Y; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS, USA., Abraham GE 3rd; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Senitko M; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Robinson TO; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS, USA., Lionakis MS; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA., Shalek AK; Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA.; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Program in Immunology, Harvard Medical School, Boston, MA, USA.; Harvard Stem Cell Institute, Cambridge, MA, USA., Ordovas-Montanes J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.; Program in Immunology, Harvard Medical School, Boston, MA, USA.; Harvard Stem Cell Institute, Cambridge, MA, USA., Horwitz BH; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.; Program in Immunology, Harvard Medical School, Boston, MA, USA.; Division of Emergency Medicine, Boston Children's Hospital, Boston, MA, USA., Glover SC; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS, USA.; Center for Immunology and Microbial Research, Department of Cell & Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA.
المصدر: MedRxiv : the preprint server for health sciences [medRxiv] 2022 Oct 26. Date of Electronic Publication: 2022 Oct 26.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE
مستخلص: Recent case reports and epidemiological data suggest fungal infections represent an under-appreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing (scRNA-seq) dataset characterizing the upper respiratory microenvironment during COVID-19, and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals, including confirmatory diagnostic testing demonstrating elevated serum (1, 3)-β-D-glucan and/or confirmed fungal culture of the predicted pathogen. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL-17 stimulation and anti-fungal immunity. Further, we observe significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggests that IL-17 stimulation - in part driven by Candida colonization - and blunted type I/III interferon signaling represents a common feature of severe COVID-19 infection.
Competing Interests: COMPETING INTERESTS A.K.S. reports compensation for consulting and/or SAB membership from Merck, Honeycomb Biotechnologies, Cellarity, Repertoire Immune Medicines, Hovione, Ochre Bio, Third Rock Ventures, FL82, Empress Therapeutics, Senda Biosciences, IntrECate Biotherapeutics, Relation Therapeutics, and Dahlia Biosciences. J.O.M. reports compensation for consulting services with Cellarity and Hovione.
معلومات مُعتمدة: T32 GM007753 United States GM NIGMS NIH HHS; P30 DK034854 United States DK NIDDK NIH HHS; R01 DE031928 United States DE NIDCR NIH HHS; T32 GM144273 United States GM NIGMS NIH HHS; RC2 DK122532 United States DK NIDDK NIH HHS; U24 AI118672 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: COVID-19; Candida; IL-17; SARS-CoV-2; anti-viral; cytokine; epithelial immunity; fungal infection; human; interferon; nasal mucosa; scRNA-seq
تواريخ الأحداث: Date Created: 20221103 Latest Revision: 20231019
رمز التحديث: 20231020
مُعرف محوري في PubMed: PMC9628205
DOI: 10.1101/2022.10.25.22281528
PMID: 36324802
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2022.10.25.22281528