tetano
Editor, Senior Moderator
J Clin Med
. 2023 Sep 27;12(19):6225.
doi: 10.3390/jcm12196225. Multi-Omic Candidate Screening for Markers of Severe Clinical Courses of COVID-19
Alexander Dutsch[SUP] 1 2 [/SUP], Carsten Uhlig[SUP] 3 [/SUP], Matthias Bock[SUP] 1 2 [/SUP], Christian Graesser[SUP] 1 2 [/SUP], Sven Schuchardt[SUP] 4 [/SUP], Steffen Uhlig[SUP] 5 [/SUP], Heribert Schunkert[SUP] 1 2 [/SUP], Michael Joner[SUP] 1 2 [/SUP], Stefan Holdenrieder[SUP] 3 [/SUP], Katharina Lechner[SUP] 1 2 [/SUP]
Affiliations
Background: Severe coronavirus disease 2019 (COVID-19) disease courses are characterized by immuno-inflammatory, thrombotic, and parenchymal alterations. Prediction of individual COVID-19 disease courses to guide targeted prevention remains challenging. We hypothesized that a distinct serologic signature precedes surges of IL-6/D-dimers in severely affected COVID-19 patients.
Methods: We performed longitudinal plasma profiling, including proteome, metabolome, and routine biochemistry, on seven seropositive, well-phenotyped patients with severe COVID-19 referred to the Intensive Care Unit at the German Heart Center. Patient characteristics were: 65 ± 8 years, 29% female, median CRP 285 ± 127 mg/dL, IL-6 367 ± 231 ng/L, D-dimers 7 ± 10 mg/L, and NT-proBNP 2616 ± 3465 ng/L.
Results: Based on time-series analyses of patient sera, a prediction model employing feature selection and dimensionality reduction through least absolute shrinkage and selection operator (LASSO) revealed a number of candidate proteins preceding hyperinflammatory immune response (denoted ΔIL-6) and COVID-19 coagulopathy (denoted ΔD-dimers) by 24-48 h. These candidates are involved in biological pathways such as oxidative stress/inflammation (e.g., IL-1alpha, IL-13, MMP9, C-C motif chemokine 23), coagulation/thrombosis/immunoadhesion (e.g., P- and E-selectin), tissue repair (e.g., hepatocyte growth factor), and growth factor response/regulatory pathways (e.g., tyrosine-protein kinase receptor UFO and low-density lipoprotein receptor (LDLR)). The latter are host- or co-receptors that promote SARS-CoV-2 entry into cells in the absence of ACE2.
Conclusions: Our novel prediction model identified biological and regulatory candidate networks preceding hyperinflammation and coagulopathy, with the most promising group being the proteins that explain changes in D-dimers. These biomarkers need validation. If causal, our work may help predict disease courses and guide personalized treatment for COVID-19.
Keywords: COVID-19 coagulopathy; COVID-19 longitudinal disease course; D-dimers; IL-6; candidate screening; hyperinflammation; multi-omics; personalization; predictive diagnostics; targeted prevention.
. 2023 Sep 27;12(19):6225.
doi: 10.3390/jcm12196225. Multi-Omic Candidate Screening for Markers of Severe Clinical Courses of COVID-19
Alexander Dutsch[SUP] 1 2 [/SUP], Carsten Uhlig[SUP] 3 [/SUP], Matthias Bock[SUP] 1 2 [/SUP], Christian Graesser[SUP] 1 2 [/SUP], Sven Schuchardt[SUP] 4 [/SUP], Steffen Uhlig[SUP] 5 [/SUP], Heribert Schunkert[SUP] 1 2 [/SUP], Michael Joner[SUP] 1 2 [/SUP], Stefan Holdenrieder[SUP] 3 [/SUP], Katharina Lechner[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37834869
- PMCID: PMC10573369
- DOI: 10.3390/jcm12196225
Background: Severe coronavirus disease 2019 (COVID-19) disease courses are characterized by immuno-inflammatory, thrombotic, and parenchymal alterations. Prediction of individual COVID-19 disease courses to guide targeted prevention remains challenging. We hypothesized that a distinct serologic signature precedes surges of IL-6/D-dimers in severely affected COVID-19 patients.
Methods: We performed longitudinal plasma profiling, including proteome, metabolome, and routine biochemistry, on seven seropositive, well-phenotyped patients with severe COVID-19 referred to the Intensive Care Unit at the German Heart Center. Patient characteristics were: 65 ± 8 years, 29% female, median CRP 285 ± 127 mg/dL, IL-6 367 ± 231 ng/L, D-dimers 7 ± 10 mg/L, and NT-proBNP 2616 ± 3465 ng/L.
Results: Based on time-series analyses of patient sera, a prediction model employing feature selection and dimensionality reduction through least absolute shrinkage and selection operator (LASSO) revealed a number of candidate proteins preceding hyperinflammatory immune response (denoted ΔIL-6) and COVID-19 coagulopathy (denoted ΔD-dimers) by 24-48 h. These candidates are involved in biological pathways such as oxidative stress/inflammation (e.g., IL-1alpha, IL-13, MMP9, C-C motif chemokine 23), coagulation/thrombosis/immunoadhesion (e.g., P- and E-selectin), tissue repair (e.g., hepatocyte growth factor), and growth factor response/regulatory pathways (e.g., tyrosine-protein kinase receptor UFO and low-density lipoprotein receptor (LDLR)). The latter are host- or co-receptors that promote SARS-CoV-2 entry into cells in the absence of ACE2.
Conclusions: Our novel prediction model identified biological and regulatory candidate networks preceding hyperinflammation and coagulopathy, with the most promising group being the proteins that explain changes in D-dimers. These biomarkers need validation. If causal, our work may help predict disease courses and guide personalized treatment for COVID-19.
Keywords: COVID-19 coagulopathy; COVID-19 longitudinal disease course; D-dimers; IL-6; candidate screening; hyperinflammation; multi-omics; personalization; predictive diagnostics; targeted prevention.