ABSTRACT
Diabetes mellitus (DM) is associated with a greater risk of COVID-19 and an increased mortality when the disease is contracted. Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear. Our aim was to explore the effects of metformin on markers of inflammation, oxidative stress, and hypercoagulability, and on clinical outcomes. Patients with DM on metformin (n = 34) and metformin naïve (n = 41), and patients without DM (n = 73) were enrolled within 48 h of hospital admission for COVID-19. Patients on metformin compared to naïve patients had a lower white blood cell count (p = 0.02), d-dimer (p = 0.04), urinary 11-dehydro thromboxane B2 (p = 0.01) and urinary liver-type fatty acid binding protein (p = 0.03) levels and had lower sequential organ failure assessment score (p = 0.002), and intubation rate (p = 0.03), fewer hospitalized days (p = 0.13), lower in-hospital mortality (p = 0.12) and lower mortality plus nonfatal thrombotic event occurrences (p = 0.10). Patients on metformin had similar clinical outcomes compared to patients without DM. In a multiple regression analysis, metformin use was associated with less days in hospital and lower intubation rate. In conclusion, metformin treatment in COVID-19 patients with DM was associated with lower markers of inflammation, renal ischemia, and thrombosis, and fewer hospitalized days and intubation requirement. Further focused studies are required to support these findings.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , Diabetes Mellitus , Hypoglycemic Agents , Metformin , Thrombosis , COVID-19/mortality , Diabetes Mellitus/drug therapy , Hospitalization , Humans , Hypoglycemic Agents/therapeutic use , Inflammation/complications , Inflammation/drug therapy , Metformin/therapeutic use , Oxidative Stress/drug effects , Retrospective Studies , Thrombosis/drug therapyABSTRACT
Standard biomarkers have been widely used for COVID-19 diagnosis and prognosis. We hypothesize that thrombogenicity metrics measured by thromboelastography will provide better diagnostic and prognostic utility versus standard biomarkers in COVID-19 positive patients. In this observational prospective study, we included 119 hospitalized COVID-19 positive patients and 15 COVID-19 negative patients. On admission, we measured standard biomarkers and thrombogenicity using a novel thromboelastography assay (TEG-6s). In-hospital all-cause death and thrombotic occurrences (thromboembolism, myocardial infarction and stroke) were recorded. Most COVID-19 patients were African--Americans (68%). COVID-19 patients versus COVID-19 negative patients had higher platelet-fibrin clot strength (P-FCS), fibrin clot strength (FCS) and functional fibrinogen level (FLEV) (Pâ≤â0.003 for all). The presence of high TEG-6âs metrics better discriminated COVID-19 positive from negative patients. COVID-19 positive patients with sequential organ failure assessment (SOFA) score at least 3 had higher P-FCS, FCS and FLEV than patients with scores less than 3 (Pâ≤â0.001 for all comparisons). By multivariate analysis, the in-hospital composite endpoint occurrence of death and thrombotic events was independently associated with SOFA score more than 3 [odds ratio (OR)â=â2.9, Pâ=â0.03], diabetes (ORâ=â3.3, Pâ=â0.02) and FCSâ>â40âmm (ORâ=â3.4, Pâ=â0.02). This largest observational study suggested the early diagnostic and prognostic utility of thromboelastography to identify COVID-19 and should be considered hypothesis generating. Our results also support the recent FDA guidance regarding the importance of measurement of whole blood viscoelastic properties in COVID-19 patients. Our findings are consistent with the observation of higher hospitalization rates and poorer outcomes for African--Americans with COVID-19.
Subject(s)
COVID-19/blood , SARS-CoV-2 , Thrombophilia/diagnosis , Adult , Black or African American/statistics & numerical data , Aged , Aged, 80 and over , Biomarkers , COVID-19/complications , COVID-19/epidemiology , COVID-19 Testing , Cardiovascular Diseases/epidemiology , Comorbidity , Diabetes Mellitus/epidemiology , Early Diagnosis , Female , Fibrin/analysis , Fibrin Clot Lysis Time , Fibrinogen/analysis , Hospitalization , Humans , Hyperlipidemias/epidemiology , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Obesity/epidemiology , Organ Dysfunction Scores , Prognosis , Prospective Studies , Thrombelastography , Thrombophilia/blood , Thrombophilia/drug therapy , Thrombophilia/etiology , Treatment Outcome , White People/statistics & numerical dataABSTRACT
Urine 11-dehydro-thromboxane B2 (u11-dh-TxB2), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and liver-type fatty acid binding protein levels (L-FABP) at the time of hospitalization were higher in coronavirus disease 2019 (COVID-19) patients with adverse events vs without events. Higher u11-dh-TxB2 and L-FABP levels were associated with longer hospitalization, more thrombotic events, and greater mortality, providing evidence for potential utility as early prognostic biomarkers for COVID-19.