Independent risk factors for COVID-19-associated coagulopathy.

OBJECTIVE: Past three years since the beginning of the outbreak, we have obtained satisfactory data on COVID-19. However, data on risk factors of COVID-19-associated coagulopathy (CAC) are extremely limited. Prediction of CAC might be a game changer since it is related to poor prognosis. Seeking independent risk factors for CAC was the main aim of the study. PATIENTS AND METHODS: 510 hospitalized COVID-19 patients were retrospectively screened. Forty-eight of them were excluded due to irrelevant D-dimer or ferritin elevation. The remaining patients were stratified into three groups as overt coagulopathy, significant pulmonary microthrombosis, and patients without coagulopathy. The overt coagulopathy group included cases with macrothrombosis or disseminated intravascular coagulation (DIC). The significant pulmonary microthrombosis group covered the cases that had clinical deterioration with simultaneous marked D-dimer elevation. The group of patients without coagulopathy included the asymptomatic patients with normal or elevated D-dimer levels. RESULTS: Overt coagulopathy developed in 3.2% and significant pulmonary microthrombosis in 10.1% of the patients. In the multivariate analysis, not receiving low molecular weight heparin (LMWH) (p=0.002), a level of D-dimer >15,000 U/ml (p=0.013) were associated with overt coagulopathy. In addition, levels of initial LDH >480 IU/L (p=0.022) and initial ferritin >1,000 ng/ml (p=0.036) were associated with significant pulmonary microthrombosis. Not receiving LMWH (p=0.001) was also associated with significant pulmonary microthrombosis, when multivariate analysis was performed by the parameters with a p-value <0.1 in the univariate analysis. Furthermore, all cases with DIC had Gram-negative bacterial sepsis. CONCLUSIONS: Not receiving LMWH, high levels of D-dimer, initial LDH, and initial ferritin are independent risk factors for CAC. DIC does not appear to develop based on COVID-19.

The effect of hereditary thrombotic factors and comorbidities on the severity of COVID-19 disease.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and presents critical challenges for public health. Due to its chronic and systemic course, COVID-19 is currently accepted as a multi-systemic infectious disease. Here we explore the possible association between disease course and hereditary thrombotic factors and comorbidities. PATIENTS AND METHODS: The patients admitted to the COVID-19 center in the Istanbul Faculty of Medicine were recruited for the study. The patients were classified according to the clinical course, severe vs. mild. Five polymorphic loci were analyzed by multiplex PCR: Factor V Leiden (FVL), FII G20210A, Beta-fibrinogen G-455A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. RESULTS: FII G20210A and Beta-fibrinogen G-455A genotypes were significantly higher in the study group compared to the literature. Wildtype genotype (GG) in Factor V Leiden locus was significantly associated with low D-Dimer levels (p =0.013). The GA genotype increased the D-Dimer levels 2.55-times compared to the GG genotype (p =0.003). Moreover, the Beta-fibrinogen G-455G genotype was significantly higher in the LDH>250 group (p =0.046). CONCLUSIONS: The presence of solid tumors in patients with COVID-19 was related to the severity of the disease course. No evidence of a correlation between the severity of the disease and all five thrombotic mutations was found, whereas the FII G20210A and Beta-fibrinogen G-455A mutations were significantly high compared to previously reported Turkish population data and global carrier rates. This finding will need to be verified by further studies with larger samples since it may reflect a likelihood of having the COVID-19 disease. The high carrier frequency of FVL mutation was more likely present in the D-dimer high group generating an increase in the D-dimer levels 2.55-times compared to the wildtype.

Severe vitamin D deficiency is associated with endothelial inflammation in healthy individuals even in the absence of subclinical atherosclerosis.

OBJECTIVE: Vitamin D has beneficial effects, some of which involve the cardiovascular system. No study to date has investigated the association between serum endocan levels, as a biomarker of endothelial inflammation, and vitamin D levels in the absence of subclinical atherosclerosis detected by carotid intima-media thickness (CIMT) in healthy individuals. PATIENTS AND METHODS: Subjects were categorized into three groups based on vitamin D levels according to Endocrine Society guidelines. Mean CIMT was calculated from six measurements on two scans. Statistical significance was set at p < 0.05, and all testing was two-sided. RESULTS: The concentration of serum endocan was 802.8 ± 411.4 ng/L in the group with the lowest serum vitamin D level, 454.8 ± 334.3 ng/L in the mild/moderately low serum vitamin D level group, and 269.4 ± 180.2 ng/L in the group with normal serum vitamin D levels (p < 0.01). Receiver operating characteristics curve analysis revealed that a serum vitamin D concentration of 7.5 ng/mL had a 97% sensitivity and 81% specificity for the prediction of serum endocan level greater than 270 ng/L, which could be an indicator for endothelial inflammation. CONCLUSIONS: Demonstrating that vitamin D deficiency can cause endothelial damage in the early period of atherosclerosis without the development of clinical cardiovascular disease will have a pivotal role in the prevention of cardiovascular mortality and morbidity.

Older Adults Hospitalized with Covid-19: Clinical Characteristics and Early Outcomes from a Single Center in Istanbul, Turkey.

OBJECTIVE: Older adults have been continuously reported to be at higher risk for adverse outcomes of Covid-19. We aimed to describe clinical characteristics and early outcomes of the older Covid-19 patients hospitalized in our center comparatively with the younger patients, and also to analyze the triage factors that were related to the in-hospital mortality of older adults. DESIGN: Retrospective; observational study. SETTING: Istanbul Faculty of Medicine hospital, Turkey. PARTICIPANTS: 362 hospitalized patients with laboratory-confirmed Covid-19 from March 11 to May 11, 2020. MEASUREMENTS: The demographic information; associated comorbidities; presenting clinical, laboratory, radiological characteristics on admission and outcomes from the electronic medical records were analyzed comparatively between the younger (<65 years) and older (≥65 years) adults. Factors associated with in-hospital mortality of the older adults were analyzed by multivariate regression analyses. RESULTS: The median age was 56 years (interquartile range [IQR], 46-67), and 224 (61.9%) were male. There were 104 (28.7%) patients ≥65 years of age. More than half of the patients (58%) had one or more chronic comorbidity. The three most common presenting symptoms in the older patients were fatigue/myalgia (89.4%), dry cough (72.1%), and fever (63.5%). Cough and fever were significantly less prevalent in older adults compared to younger patients (p=0.001 and 0.008, respectively). Clinically severe pneumonia was present in 31.5% of the study population being more common in older adults (49% vs. 24.4%) (p<0.001). The laboratory parameters that were significantly different between the older and younger adults were as follows: the older patients had significantly higher CRP, D-dimer, TnT, pro-BNP, procalcitonin levels, higher prevalence of lymphopenia, neutrophilia, increased creatinine, and lower hemoglobin, ALT, albumin level (p<0.05). In the radiological evaluation, more than half of the patients (54.6%) had moderate-severe pneumonia, which was more prevalent in older patients (66% vs. 50%) (p=0.006). The adverse outcomes were significantly more prevalent in older adults compared to the younger patients (ICU admission, 28.8% vs. 8.9%; mortality, 23.1% vs. 4.3%, p<0.001). Among the triage evaluation parameters, the only factor associated with higher mortality was the presence of clinically severe pneumonia on admission (Odds Ratio=12.3, 95% confidence interval=2.7-55.5, p=0.001). CONCLUSION: Older patients presented with more prevalent chronic comorbidities, less prevalent symptomatology but more severe respiratory signs and laboratory abnormalities than the younger patients. Among the triage assessment factors, the clinical evaluation of pulmonary involvement came in front to help clinicians to stratify the patients for mortality risk.