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Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19.
Leisman, Daniel E; Mehta, Arnav; Thompson, B Taylor; Charland, Nicole C; Gonye, Anna L K; Gushterova, Irena; Kays, Kyle R; Khanna, Hargun K; LaSalle, Thomas J; Lavin-Parsons, Kendall M; Lilley, Brendan M; Lodenstein, Carl L; Manakongtreecheep, Kasidet; Margolin, Justin D; McKaig, Brenna N; Rojas-Lopez, Maricarmen; Russo, Brian C; Sharma, Nihaarika; Tantivit, Jessica; Thomas, Molly F; Parry, Blair Alden; Villani, Alexandra-Chloé; Sade-Feldman, Moshe; Hacohen, Nir; Filbin, Michael R; Goldberg, Marcia B.
  • Leisman DE; Department of Anesthesiology, Critical Care, and Pain Medicine.
  • Mehta A; Department of Medicine.
  • Thompson BT; Massachusetts General Hospital Cancer Center.
  • Charland NC; Department of Medicine.
  • Gonye ALK; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts; and.
  • Gushterova I; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Kays KR; Department of Medicine.
  • Khanna HK; Department of Medicine.
  • LaSalle TJ; Department of Emergency Medicine, and.
  • Lavin-Parsons KM; Center for Cancer Research.
  • Lilley BM; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts; and.
  • Lodenstein CL; Center for Cancer Research.
  • Manakongtreecheep K; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts; and.
  • Margolin JD; Department of Emergency Medicine, and.
  • McKaig BN; Department of Emergency Medicine, and.
  • Rojas-Lopez M; Center for Cancer Research.
  • Russo BC; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts; and.
  • Sharma N; Department of Emergency Medicine, and.
  • Tantivit J; Department of Emergency Medicine, and.
  • Thomas MF; Department of Emergency Medicine, and.
  • Parry BA; Center for Cancer Research.
  • Villani AC; Center for Immunology and Inflammatory Diseases, and.
  • Sade-Feldman M; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts; and.
  • Hacohen N; Department of Emergency Medicine, and.
  • Filbin MR; Department of Emergency Medicine, and.
  • Goldberg MB; Center for Bacterial Pathogenesis, Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Am J Respir Crit Care Med ; 205(5): 507-519, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1560818
ABSTRACT
Rationale Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time.

Objectives:

To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes.

Methods:

This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. More than 40 markers of alveolar (including receptor for advanced glycation endproducts [RAGE]), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, and troponin-I) were serially compared between invasively and spontaneously ventilated patients using mixed-effects repeated-measures models. Ventilatory ratios were calculated for intubated patients. Associations of biomarkers with modified World Health Organization scale at Day 28 were determined with multivariable proportional-odds regression. Measurements and Main

Results:

Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.80-fold higher in invasive ventilation patients at Day 0 (95% confidence interval [CI], 1.50-2.17) versus spontaneous ventilation, but decreased over time in all patients. Changes in alveolar markers did not correlate with changes in endothelial, cardiac, or renal injury markers. In contrast, endothelial markers were similar to lower at Day 0 for invasive ventilation versus spontaneous ventilation, but then increased over time only among intubated patients. In intubated patients, angiopoietin-2 was similar (fold difference, 1.02; 95% CI, 0.89-1.17) to nonintubated patients at Day 0 but 1.80-fold higher (95% CI, 1.56-2.06) at Day 3; cardiorenovascular injury markers showed similar patterns. Endothelial markers were not consistently associated with ventilatory ratios. Endothelial markers were more often significantly associated with 28-day outcomes than alveolar markers.

Conclusions:

Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to disease progression in severe COVID-19.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pulmonary Alveoli / Respiratory Distress Syndrome / Endothelium / Alveolar Epithelial Cells / Patient Acuity / COVID-19 Type of study: Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Am J Respir Crit Care Med Journal subject: Critical Care Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pulmonary Alveoli / Respiratory Distress Syndrome / Endothelium / Alveolar Epithelial Cells / Patient Acuity / COVID-19 Type of study: Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Am J Respir Crit Care Med Journal subject: Critical Care Year: 2022 Document Type: Article