Trajectories of host-response biomarkers and inflammatory subphenotypes in COVID-19 patients across the spectrum of respiratory support.
medRxiv
; 2022 Nov 29.
Article
em En
| MEDLINE
| ID: mdl-36482978
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
MedRxiv
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos