A multicenter study of asymmetric and symmetric dimethylarginine as predictors of mortality risk in hospitalized COVID-19 patients

TY - JOUR

T1 - A multicenter study of asymmetric and symmetric dimethylarginine as predictors of mortality risk in hospitalized COVID-19 patients

AU - Hannemann, Juliane

AU - Zink, Anne

AU - Mileva, Yoana

AU - Balfanz, Paul

AU - Dahl, Edgar

AU - Volland, Sonja

AU - Illig, Thomas

AU - Schwedhelm, Edzard

AU - Kurth, Florian

AU - Stege, Alexandra

AU - Aepfelbacher, Martin

AU - Hoffmann, Armin

AU - Böger, Rainer

N1 - © 2024. The Author(s).

PY - 2024/7/8

Y1 - 2024/7/8

N2 - Mortality of patients hospitalized with COVID-19 has remained high during the consecutive SARS-CoV-2 pandemic waves. Early discrimination of patients at high mortality risk is crucial for optimal patient care. Symmetric (SDMA) and asymmetric dimethylarginine (ADMA) have been proposed as possible biomarkers to improve risk prediction of COVID-19 patients. We measured SDMA, ADMA, and other L-arginine-related metabolites in 180 patients admitted with COVID-19 in four German university hospitals as compared to 127 healthy controls. Patients were treated according to accepted clinical guidelines and followed-up until death or hospital discharge. Classical inflammatory markers (leukocytes, CRP, PCT), renal function (eGFR), and clinical scores (SOFA) were taken from hospital records. In a small subgroup of 23 COVID-19 patients, sequential blood samples were available and analyzed for biomarker trends over time until 14 days after admission. Patients had significantly elevated SDMA, ADMA, and L-ornithine and lower L-citrulline concentrations than controls. Within COVID-19 patients, SDMA and ADMA were significantly higher in non-survivors (n = 41, 22.8%) than in survivors. In ROC analysis, the optimal cut-off to discriminate non-survivors from survivors was 0.579 µmol/L for SDMA and 0.599 µmol/L for ADMA (both p < 0.001). High SDMA and ADMA were associated with odds ratios for death of 11.45 (3.37-38.87) and 5.95 (2.63-13.45), respectively. Analysis of SDMA and ADMA allowed discrimination of a high-risk (mortality, 43.7%), medium-risk (15.1%), and low-risk group (3.6%); risk prediction was significantly improved over classical laboratory markers. We conclude that analysis of ADMA and SDMA after hospital admission significantly improves risk prediction in COVID-19.

AB - Mortality of patients hospitalized with COVID-19 has remained high during the consecutive SARS-CoV-2 pandemic waves. Early discrimination of patients at high mortality risk is crucial for optimal patient care. Symmetric (SDMA) and asymmetric dimethylarginine (ADMA) have been proposed as possible biomarkers to improve risk prediction of COVID-19 patients. We measured SDMA, ADMA, and other L-arginine-related metabolites in 180 patients admitted with COVID-19 in four German university hospitals as compared to 127 healthy controls. Patients were treated according to accepted clinical guidelines and followed-up until death or hospital discharge. Classical inflammatory markers (leukocytes, CRP, PCT), renal function (eGFR), and clinical scores (SOFA) were taken from hospital records. In a small subgroup of 23 COVID-19 patients, sequential blood samples were available and analyzed for biomarker trends over time until 14 days after admission. Patients had significantly elevated SDMA, ADMA, and L-ornithine and lower L-citrulline concentrations than controls. Within COVID-19 patients, SDMA and ADMA were significantly higher in non-survivors (n = 41, 22.8%) than in survivors. In ROC analysis, the optimal cut-off to discriminate non-survivors from survivors was 0.579 µmol/L for SDMA and 0.599 µmol/L for ADMA (both p < 0.001). High SDMA and ADMA were associated with odds ratios for death of 11.45 (3.37-38.87) and 5.95 (2.63-13.45), respectively. Analysis of SDMA and ADMA allowed discrimination of a high-risk (mortality, 43.7%), medium-risk (15.1%), and low-risk group (3.6%); risk prediction was significantly improved over classical laboratory markers. We conclude that analysis of ADMA and SDMA after hospital admission significantly improves risk prediction in COVID-19.

KW - Humans

KW - Arginine/analogs & derivatives

KW - COVID-19/mortality

KW - Male

KW - Female

KW - Middle Aged

KW - Aged

KW - Biomarkers/blood

KW - Hospitalization

KW - SARS-CoV-2/isolation & purification

KW - Germany/epidemiology

KW - Prognosis

KW - Adult

KW - Aged, 80 and over

KW - Risk Factors

U2 - 10.1038/s41598-024-66288-3

DO - 10.1038/s41598-024-66288-3

M3 - SCORING: Journal article

C2 - 38977837

VL - 14

SP - 15739

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -