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Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium.
Ziegler, Carly G K; Owings, Anna H; Miao, Vincent N; Navia, Andrew W; Tang, Ying; Bromley, Joshua D; Lotfy, Peter; Sloan, Meredith; Laird, Hannah; Williams, Haley B; George, Micayla; Drake, Riley S; Pride, Yilianys; Abraham, George E; Senitko, Michal; Robinson, Tanya O; Lionakis, Michail S; Shalek, Alex K; Ordovas-Montanes, Jose; Horwitz, Bruce H; Glover, Sarah C.
Afiliação
  • Ziegler CGK; Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA, USA.
  • Owings AH; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Miao VN; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Navia AW; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA.
  • Tang Y; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Bromley JD; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Lotfy P; Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA, USA.
  • Sloan M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Laird H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Williams HB; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • George M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Drake RS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pride Y; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Abraham GE; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Senitko M; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.
  • Robinson TO; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Lionakis MS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Shalek AK; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Ordovas-Montanes J; Department of Microbiology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Horwitz BH; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Glover SC; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.
medRxiv ; 2022 Oct 26.
Article em En | MEDLINE | ID: mdl-36324802
ABSTRACT
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)-ß-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.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article