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A functionally distinct neutrophil landscape in severe COVID-19 reveals opportunities for adjunctive therapies.
Panda, Rachita; Castanheira, Fernanda Vs; Schlechte, Jared M; Surewaard, Bas Gj; Shim, Hanjoo Brian; Zucoloto, Amanda Z; Slavikova, Zdenka; Yipp, Bryan G; Kubes, Paul; McDonald, Braedon.
  • Panda R; Snyder Institute for Chronic Diseases.
  • Castanheira FV; Department of Physiology and Pharmacology.
  • Schlechte JM; Snyder Institute for Chronic Diseases.
  • Surewaard BG; Department of Physiology and Pharmacology.
  • Shim HB; Snyder Institute for Chronic Diseases.
  • Zucoloto AZ; Department of Critical Care Medicine, and.
  • Slavikova Z; Snyder Institute for Chronic Diseases.
  • Yipp BG; Department of Microbiology, Immunology, and Infectious Diseases, Cummings School of Medicine, University of Calgary, Calgary, Alberta, Canada.
  • Kubes P; Snyder Institute for Chronic Diseases.
  • McDonald B; Department of Physiology and Pharmacology.
JCI Insight ; 7(2)2022 01 25.
Article in English | MEDLINE | ID: covidwho-1575230
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ABSTRACT
Acute respiratory distress syndrome (ARDS) is a life-threatening syndrome, constituted by respiratory failure and diffuse alveolar damage that results from dysregulated local and systemic immune activation, causing pulmonary vascular, parenchymal, and alveolar damage. SARS-CoV-2 infection has become the dominant cause of ARDS worldwide, and emerging evidence implicates neutrophils and their cytotoxic arsenal of effector functions as central drivers of immune-mediated lung injury in COVID-19 ARDS. However, key outstanding questions are whether COVID-19 drives a unique program of neutrophil activation or effector functions that contribute to the severe pathogenesis of this pandemic illness and whether this unique neutrophil response can be targeted to attenuate disease. Using a combination of high-dimensional single-cell analysis and ex vivo functional assays of neutrophils from patients with COVID-19 ARDS, compared with those with non-COVID ARDS (caused by bacterial pneumonia), we identified a functionally distinct landscape of neutrophil activation in COVID-19 ARDS that was intrinsically programmed during SARS-CoV-2 infection. Furthermore, neutrophils in COVID-19 ARDS were functionally primed to produce high amounts of neutrophil extracellular traps. Surprisingly, this unique pathological program of neutrophil priming escaped conventional therapy with dexamethasone, thereby revealing a promising target for adjunctive immunotherapy in severe COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Neutrophil Activation / Extracellular Traps / SARS-CoV-2 / COVID-19 / Neutrophils Type of study: Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Neutrophil Activation / Extracellular Traps / SARS-CoV-2 / COVID-19 / Neutrophils Type of study: Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Year: 2022 Document Type: Article