Immunothrombosis in hospitalized COVID-19 patients identified by multiomics profiling and linked to postacute complications
Post-acute sequelae of COVID-19 (PASC) disproportionately affect hospitalized patients and require improved molecular characterization to inform patient management.
Here, we performed a prospective longitudinal multi-omics study of hospitalized COVID-19 patients, analyzing whole blood transcriptomics, targeted urine metabolomics, kidney injury biomarkers, and electronic health record-based outcome stratification across acute illness, one-month, and three-month recovery time points.
Interconnected immunothrombosis-related pathways dominated the acute phase, while most immune and metabolomic pathways partially normalize. However, patients who developed long COVID exhibited a distinct blood transcriptional signature at three months consistent with an endothelial-associated activation profile, including platelet reactivity, complement dysregulation, and low-grade vascular inflammation, distinguishing them from fully recovered individuals.
This multi-omics approach identifies clinically measurable biomarkers associated with longitudinal molecular trajectories and supports post-acute risk stratification.
HIGHLIGHTS
• Severe COVID-19 induces immunothrombosis-associated molecular programs
• Acute COVID-19 is associated with mitochondrial metabolic dysregulation
• Urine profiling indicates gradual renal recovery after hospitalization
• Long COVID patients retain endothelial-associated activation signatures
Web | DOI | PDF | iScience | Open Access
Laura Ansone; Līva Pelcmane; Monta Brīvība; Rihards Saksis; Ivars Silamiķelis; Kristaps Korņejevs; Daniella Borisova; Kaspars Megnis; Līga Eliņa; Vita Rovite; Annija Vaska; Kristaps Klavins; Helgi B Schiöth; Janis Klovins
Post-acute sequelae of COVID-19 (PASC) disproportionately affect hospitalized patients and require improved molecular characterization to inform patient management.
Here, we performed a prospective longitudinal multi-omics study of hospitalized COVID-19 patients, analyzing whole blood transcriptomics, targeted urine metabolomics, kidney injury biomarkers, and electronic health record-based outcome stratification across acute illness, one-month, and three-month recovery time points.
Interconnected immunothrombosis-related pathways dominated the acute phase, while most immune and metabolomic pathways partially normalize. However, patients who developed long COVID exhibited a distinct blood transcriptional signature at three months consistent with an endothelial-associated activation profile, including platelet reactivity, complement dysregulation, and low-grade vascular inflammation, distinguishing them from fully recovered individuals.
This multi-omics approach identifies clinically measurable biomarkers associated with longitudinal molecular trajectories and supports post-acute risk stratification.
HIGHLIGHTS
• Severe COVID-19 induces immunothrombosis-associated molecular programs
• Acute COVID-19 is associated with mitochondrial metabolic dysregulation
• Urine profiling indicates gradual renal recovery after hospitalization
• Long COVID patients retain endothelial-associated activation signatures
Web | DOI | PDF | iScience | Open Access