Trajectories of host-response biomarkers and inflammatory subphenotypes in COVID-19 patients across the spectrum of respiratory support.

Autor:	Lu M; Internal Medicine Residency Program, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Drohan C; Internal Medicine Residency Program, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Bain W; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Shah FA; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Bittner M; Internal Medicine Residency Program, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Evankovich J; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Prendergast N; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Hensley M; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Suber T; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Fitzpatrick M; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Ramanan R; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Murray H; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Schaefer C; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Qin S; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, USA., Wang X; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, USA., Zhang Y; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Nouraie SM; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Gentry H; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Kessinger C; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Patel A; Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, USA., Macatangay BJ; Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA., Jacobs J; Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA., Mellors J; Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA., Lee JS; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Ray P; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Ray A; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA., Methé B; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, USA., Morris A; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, USA., McVerry BJ; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, USA., Kitsios GD; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2022 Nov 29. Date of Electronic Publication: 2022 Nov 29.
DOI:	10.1101/2022.11.28.22282858
Abstrakt:	Purpose: Enhanced understanding of the dynamic changes in the dysregulated inflammatory response in COVID-19 may help improve patient selection and timing for immunomodulatory therapies. Methods: We enrolled 323 COVID-19 inpatients on different levels of baseline respiratory support: i) Low Flow Oxygen (37%), ii) Non-Invasive Ventilation or High Flow Oxygen (NIV_HFO, 29%), iii) Invasive Mechanical Ventilation (IMV, 27%), and iv) Extracorporeal Membrane Oxygenation (ECMO, 7%). We collected plasma samples upon enrollment and days 5 and 10 to measure host-response biomarkers. We classified subjects into inflammatory subphenotypes using two validated predictive models. We examined clinical, biomarker and subphenotype trajectories and outcomes during hospitalization. Results: IL-6, procalcitonin, and Angiopoietin-2 were persistently elevated in patients at higher levels of respiratory support, whereas sRAGE displayed the inverse pattern. Patients on NIV_HFO at baseline had the most dynamic clinical trajectory, with 26% eventually requiring intubation and exhibiting worse 60-day mortality than IMV patients at baseline (67% vs. 35%, p<0.0001). sRAGE levels predicted NIV failure and worse 60-day mortality for NIV_HFO patients, whereas IL-6 levels were predictive in IMV or ECMO patients. Hyper-inflammatory subjects at baseline (<10% by both models) had worse 60-day survival (p<0.0001) and 50% of them remained classified as hyper-inflammatory on follow-up sampling at 5 days post-enrollment. Receipt of combined immunomodulatory therapies (steroids and anti-IL6 agents) was associated with markedly increased IL-6 and lower Angiopoietin-2 levels (p<0.05). Conclusions: Longitudinal study of systemic host responses in COVID-19 revealed substantial and predictive inter-individual variability, influenced by baseline levels of respiratory support and concurrent immunomodulatory therapies.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu