Biochemical, Biophysical, and Immunological Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections
Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We find the percent solids and protein content are greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibit heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observe increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factorâ€"stimulated gene-6 (TSG6) staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicate that increases in HA and DNA in COVID-19 respiratory secretion samples correlate with enhanced inflammatory burden and suggest that DNA and HA may be viable therapeutic targets in COVID-19 infection.
Errataetall: | |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - year:2022 |
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Enthalten in: |
medRxiv : the preprint server for health sciences - (2022) vom: 04. Apr. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Kratochvil, Michael J [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Revised 16.07.2022 published: Electronic UpdateIn: JCI Insight. 2022 Jun 22;7(12):. - PMID 35730564 Citation Status PubMed-not-MEDLINE |
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doi: |
10.1101/2022.03.28.22272848 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM339409401 |
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500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We find the percent solids and protein content are greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibit heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observe increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factorâ€"stimulated gene-6 (TSG6) staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicate that increases in HA and DNA in COVID-19 respiratory secretion samples correlate with enhanced inflammatory burden and suggest that DNA and HA may be viable therapeutic targets in COVID-19 infection | ||
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700 | 1 | |a Demirdjian, Sally |e verfasserin |4 aut | |
700 | 1 | |a Cai, Pamela C |e verfasserin |4 aut | |
700 | 1 | |a Burgener, Elizabeth B |e verfasserin |4 aut | |
700 | 1 | |a Nagy, Nadine |e verfasserin |4 aut | |
700 | 1 | |a Barlow, Graham L |e verfasserin |4 aut | |
700 | 1 | |a Popescu, Medeea |e verfasserin |4 aut | |
700 | 1 | |a Nicolls, Mark R |e verfasserin |4 aut | |
700 | 1 | |a Ozawa, Michael G |e verfasserin |4 aut | |
700 | 1 | |a Regula, Donald P |e verfasserin |4 aut | |
700 | 1 | |a Pacheco-Navarro, Ana E |e verfasserin |4 aut | |
700 | 1 | |a Yang, Samuel |e verfasserin |4 aut | |
700 | 1 | |a de Jesus Perez, Vinicio A |e verfasserin |4 aut | |
700 | 1 | |a Karmouty-Quintana, Harry |e verfasserin |4 aut | |
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700 | 1 | |a Zhao, Bihong |e verfasserin |4 aut | |
700 | 1 | |a Buja, Maximilian L |e verfasserin |4 aut | |
700 | 1 | |a Johnson, Pamela Y |e verfasserin |4 aut | |
700 | 1 | |a Vernon, Robert B |e verfasserin |4 aut | |
700 | 1 | |a Wight, Thomas N |e verfasserin |4 aut | |
700 | 0 | |a Stanford COVID-19 Biobank Study Group |e verfasserin |4 aut | |
700 | 1 | |a Milla, Carlos E |e verfasserin |4 aut | |
700 | 1 | |a Rogers, Angela J |e verfasserin |4 aut | |
700 | 1 | |a Spakowitz, Andrew J |e verfasserin |4 aut | |
700 | 1 | |a Heilshorn, Sarah C |e verfasserin |4 aut | |
700 | 1 | |a Bollyky, Paul L |e verfasserin |4 aut | |
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