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

PurposeEnhanced understanding of the dynamic changes in the dysregulated inflammatory response in COVID-19 may help improve patient selection and timing for immunomodulatory therapies.MethodsWe 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.ResultsIL-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%, pConclusionsLongitudinal 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.