Heparin therapy in COVID-19: Call for randomized controlled trials (RCTs).

Coronavirus disease 2019 (COVID-19) is associated with increases in abnormal coagulation, and particularly D-dimer (D-D) levels. Heparin therapy has been recommended as pharmacologic thromboprophylaxis in patients hospitalized with COVID-19; however, data on its efficacy are lacking. The current study retrospectively analyzed changes in blood coagulation and the impact of heparin therapy. Medical records of 593 patients with confirmed COVID-19 were collected. On admission, elevated fibrinogen (Fg) levels were noted in with 42.2% (250/593) of patients, followed by increases in D-D (28.5%) and a prolonged prothrombin time (PT) (23.9%). Patients with severe/critical COVID-19 had a higher proportion of abnormal coagulation parameters than patients with mild/ordinary COVID-19. Dynamic changes in coagulation parameters were plotted on timeline charts for 97 patients with COVID-19 after heparin treatment. These changes, when combined with Fg, PT, D-D, and other indicators, may provide a relatively comprehensive description of coagulation abnormalities. Heparin seems to be important in the treatment of patients with COVID-19 based on the current findings. The efficacy of heparin in the treatment of COVID-19 should be confirmed by randomized controlled trials (RCTs) as soon as possible.

Corticosteroid Treatment Prevents Lipopolysaccharide-Induced Increase of ACE2 and Reduces Fibrin Degradation Products in Bronchoalveolar Lavage Fluid.

The assessment of systemic corticosteroid effects on intrapulmonary disease biomarkers is challenging. This retrospective evaluation of a human endotoxemia model quantified ACE2 and fibrin degradation product (FDP) concentrations in bronchoalveolar lavage fluid (BALF) samples from a randomized, double-blind, placebo-controlled study (NCT01714427). Twenty-four healthy volunteers received either 2 × 40 mg intravenous dexamethasone or placebo. These doses were administered 12 h apart prior to bronchoscopy-guided intrabronchial lipopolysaccharide (LPS) stimulation (control: saline into the contralateral lung segment). We quantified ACE2 concentration, the Angiotensin-II-to-Angiotensin-1-7 conversion rate as well as FDP in BALF 6 h after LPS instillation. In placebo-treated subjects, LPS instillation increased ACE2 concentrations compared to unstimulated lung segments [1,481 (IQR: 736-1,965) vs. 546 (413-988) pg/mL; p = 0.016]. Dexamethasone abolished the increase in ACE2 concentrations (p=0.13). Accordingly, LPS instillation increased the Angiotensin-II-to-Angiotensin-1-7 conversion capacity significantly in the placebo cohort, indicating increased enzymatic activity (p = 0.012). FDP increased following LPS-instillation [8.9 (2.7-12.2) vs. 6.6 (0.9-9.6) ng/mL, p = 0.025] in the placebo group, while dexamethasone caused a shut-down of fibrinolysis in both lung segments. LPS instillation increased ACE2 concentration, its enzymatic activity and FDP, which was mitigated by systemic dexamethasone treatment. Our results strengthen previously published findings regarding the efficiency of corticosteroids for the treatment of COVID-19-induced acute lung injury.

Role of Coagulation Profile in Predicting Disease Severity Among Patients of COVID-19.

Background Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), affects the coagulation cascade. In this retrospective study, we aimed to analyze the association of different coagulation parameters including that of D-dimer, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT) with severity in COVID-19 patients. Methodology A total of 90 patients positive for SARS-CoV-2 on real-time reverse transcription-polymerase chain reaction (rRT-PCR) were included in the study. The patients were categorized as severe and non-severe, and their D-dimer, fibrinogen, PT, and aPTT values on admission were evaluated. The association of the coagulation parameters with disease severity was analyzed by independent t-test and Chi-square test. The cut-off values of these parameters were calculated to predict the disease severity by receiver operator characteristic (ROC) curve. Results Out of 90 patients admitted, 42 patients were categorized as severe and the rest 48 patients were categorized as non-severe. D-dimer, fibrinogen, and PT in the severe group were significantly higher than the non-severe group with p-values of <0.001, 0.005, and <0.001, respectively. Cut-off values of 0.99 mg/L for D-dimer,349.5 mg/dL for fibrinogen, and 13.05 seconds for PT were predictive of disease severity among COVID-19 patients. Conclusion Severe COVID-19 patients showed significantly higher levels of D-dimer and fibrinogen and prolongation of PT as compared to non-severe COVID-19 patients. Higher levels of D-dimer and fibrinogen, and prolonged PT are predictive of increased disease severity among COVID-19 patients.

Prolonged prothrombin time at admission predicts poor clinical outcome in COVID-19 patients.

BACKGROUND: The prognostic value of coagulation disorder in coronavirus disease 2019 (COVID-19) patients should be demonstrated. AIM: To investigate the abnormalities of coagulation parameters in the patients with COVID-19 and their prognostic values. METHODS: Consecutive patients admitted in the isolation ward of Renmin Hospital of Wuhan University from January 31 to February 5, 2020 with confirmed COVID-19 were included. The primary outcomes were death and survival as of March 11. Demographics, vital signs, comorbidities and laboratory tests were collected and compared between those who died and survivors. Logistic regression analysis for prognostic factors was performed. Kaplan-Meier analysis was used to compare the estimated survival rate between patients with prolonged prothrombin time and normal prothrombin time. RESULTS: The total number of patients with confirmed COVID-19 who were enrolled was 213. The median age was 62 years, and 95 patients (44.6%) were men. Fifty-one patients were critical (23.9%), 79 patients were severe (37.1%) and 83 patients were moderate (39%). As of March 11, 2020, 99 patients were discharged (46.5%), 79 patients (37.1%) stayed in the hospital and 35 patients (16.2%) died. Median time to death was 6 (4-8) d, while median hospital stay was 32 (22-36) d in survivors (P < 0.001). More men (P = 0.002) and elderly patients (P < 0.001) were found in the group of those who died. The respiration rate at admission was higher in the group of those who died (P < 0.001). The incidences of hypertension (P = 0.028), cerebrovascular disease (P < 0.001), chronic kidney disease (P = 0.02) and chronic obstructive pulmonary disease (P < 0.001) were higher in the group of those who died. Platelet count was decreased in the group of those who died (P = 0.002) whereas prothrombin time (P < 0.001), activated partial thromboplastin time (P = 0.033), concentration of D-dimer (P < 0.001) and fibrin degradation products (P < 0.001) were increased in the group of those who died. Prothrombin time [odds ratio (OR): 2.19, P = 0.004], respiration rate (OR: 1.223, P < 0.001), age (OR: 1.074, P < 0.001) and fibrin degradation products concentration (OR: 1.02, P = 0.014) were predictors of death. The survival rate was significantly lower in patients with prolonged prothrombin time compare to those with normal prothrombin time (P < 0.001). CONCLUSION: Prothrombin time, concentration of fibrin degradation products, respiration rate and age were predictive factors for clinical outcomes of COVID-19 patients.

Coronavirus disease 2019 and cardiovascular system: A narrative review.

At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.