scholarly journals Targeting the Endothelium in the Treatment of COVID-19 Early Clinical Stages: Results of a Randomized Placebo-Controlled Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 667-667
Author(s):  
Alejandro Gonzalez-Ochoa
Keyword(s):  
Placebo Group ◽  
Hospital Care ◽  
Controlled Trial ◽  
Serum Levels ◽  
Supplemental Oxygen ◽  
Thromboembolic Events ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Clinical Stages ◽  
D Dimer

Abstract Background: SARS-CoV-2 can induce several vascular endothelial-dependent systemic complications and treatment targeting endothelial cells has been suggested. Sulodexide is a heparin and glycosaminoglycan compound that has pleiotropic properties within the vascular endothelium that can prove beneficial in COVID-19 patients. Aims: We aimed to evaluate the effect of sulodexide when used in the early clinical stages of COVID-19. Methods: In an outpatient setting, we conducted a randomized placebo-controlled trial. Key inclusion criteria were patients within three days of COVID-19 clinical onset and being deemed at high risk (> 50%) of severe clinical disease progression. The risk was assessed using the COVID-19 Health Complication (C19HC) calculator, which clusters the importance of various chronic comorbidities into a percentage value. After inclusion, patients were randomly assigned to receive an oral dose of sulodexide (500 LRU twice a day) or a placebo for 21 days. We performed follow-ups to assess the study endpoints via remote communication with participants or household members every seven days or as deemed necessary. Participants continued the standard of care under the supervision of their healthcare provider's primary physician. The need for hospital care was the primary outcome. Also evaluated, were the need for supplemental oxygen support, D-dimer and C reactive protein (CRP) serum levels, thromboembolic events, and mortality. Physicians responsible to determine the need for hospital care or supplemental oxygen at home were blinded to group allocation. This trial was conducted throughout the regional lockdown caused by the first wave of COVID-19 which caused some unforeseen limitations during the trial. Differences in means were calculated using the Student's t-test, while differences in percentages were assessed using the χ 2 test. Before and after serum levels in the same patients were analyzed using two paired t-tests. If the data were not normally distributed, a Wilcoxon test was used. A Kaplan-Meier curve was used to graphically compare time-to-endpoint for hospital admission and mortality. Results: 312 patients were included in the intent to treat analysis. At 21 days follow-up, 23 of 155 patients required hospitalization in the sulodexide group compared to 38 of 157 in the placebo group [relative risk (RR), 0.6; 95% confidence interval (CI), 0.38-0.97; p=0.037]. The benefit persisted with a per-protocol analysis (RR 0.6, p=0.031). Fewer patients required oxygen support in the sulodexide group [39 of 155 vs. 56 of 157; RR, 0.61; 95% CI, 0.38 to 0.9; p=0.04], and for fewer days (9 ± 7.2 in the sulodexide group vs. 11.5 ± 9.6 in the placebo group; p=0.02). Mean D-dimer levels at week 2 were significantly higher in the placebo group than in the sulodexide group (p < 0.01). 28 of the 155 patients (18%) in the sulodexide group showed a D-dimer value > 500 ng/dl, compared to 59 out of 157 (37.5%) in the placebo group (RR of 0.48; 95% CI of 0.31 to 0.67; p > 0.01). Mean C-reactive protein levels at week 2 were lower in the sulodexide group than in the placebo group (p < 0.01). There was no between-group difference concerning, hospital length of stay, thromboembolic events, major bleeding, or mortality. Conclusions: Early intervention on COVID-19 patients with sulodexide resulted in a reduced need for supplemental oxygen and hospital care. The synergistic activity of sulodexide's antithrombotic and non-antithrombotic effects on different biological targets may play an essential role in limiting disease progression. Added a low risk of bleeding or significant side effects, sulodexide might be an alternative to other oral anticoagulants which makes it a valuable medication in the outpatient treatment of COVID-19. Disclosures Gonzalez-Ochoa: Alfasigma: Consultancy, Research Funding; servier: Consultancy.

The Value of D-Dimer in Patients with Increased C-Reactive Protein Suspected of Pulmonary Embolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5056-5056
Author(s):  
Claire Siemes ◽  
Paul Berendes ◽  
Frans van der Straaten ◽  
Ton Cleophas ◽  
Mark-David Levin
Keyword(s):  
Pulmonary Embolism ◽  
Conflicts Of Interest ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Serum Levels ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Interaction Term ◽  
Pulmonary Embolisms ◽  
D Dimer

Abstract Abstract 5056 OBJECTIVE To investigate the relation between elevated levels of C-reactive protein (CRP) and D-dimer, and to study whether D-dimer levels can be interpreted in relation to elevated levels of CRP in the prediction of a pulmonary embolism in order to increase its specificity without decline in sensitivity. METHODS Between august 2004 and april 2007 (33 months) serum levels of C-reactive protein (mmol/L) and D-dimer (mmol/L) were cross-sectionally collected and pulmonary embolisms on CT-angiograms were scored within 48 hours. The study was devided into three parts. First, characteristics of excluded persons were studied. Second, the correlation between CRP and D-dimer level was considered in those with a defined (i.e. values with < and > symbols excluded) biomarker level. Finally, the effect of CRP level on the sensitivity of D-dimer for pulmonary embolisms was examined. RESULTS CRP and D-dimer levels were positively correlated ( r = 0.37; p < 0.001), and both were increased in persons with a pulmonary embolism (CRP: p = 0.02; D-dimer: p < 0.001). 14 % of variability in D-dimer level was explained by CRP level. Median D-dimer levels were increased in the pulmonary embolism (PE) group, however, the increase in D-dimer level by CRP quartile as was found in the non-PE was not seen in de PE-group. Adding the interaction term of CRP and D-dimer to the statistical model showed some influence on the area under the curve (AUC). Nevertheless, this was not significantly different from the model with only D-dimer levels. However, when stratified for CRP quartile, ROC-curves of the predictive effect of D-dimer on pulmonary embolisms showed a decrease in AUC by increment of CRP quartile. CONCLUSION CRP and D-dimer are positively correlated, and both predictive of PE. The predictive value of D-dimer for PE declines by increment of CRP, although this seems to be safely for a broader range of accompanied CRP levels. Disclosures No relevant conflicts of interest to declare.

scholarly journals Vitamin D and Lung Outcomes in Elderly COVID-19 Patients

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 717
Author(s):  
Alberto Sulli ◽  
Emanuele Gotelli ◽  
Andrea Casabella ◽  
Sabrina Paolino ◽  
Carmen Pizzorni ◽  
...  
Keyword(s):  
Vitamin D ◽  
Negative Correlation ◽  
Serum Levels ◽  
Pulmonary Involvement ◽  
Clinical Parameters ◽  
Lung Involvement ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Lower Vitamin ◽  
D Dimer

Background and aim: Vitamin D deficiency is frequently reported in patients with SARS-CoV-2 infection. The aim of this study was to correlate the 25OH-Vitamin D serum concentrations with clinical parameters of lung involvement, in elderly patients hospitalized for SARS-CoV-2 infection. Methods: Sixty-five consecutive COVID-19 patients (mean age 76 ± 13 years) and sixty-five sex- and age-matched control subjects (CNT) were analyzed. The following clinical parameters, including comorbidities, were collected at admission: type of pulmonary involvement, respiratory parameters (PaO2, SO2, PaCO2, PaO2/FiO2), laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein). Results: Significantly lower vitamin D serum levels were found in COVID-19 patients than in CNT (median 7.9 vs 16.3 ng/mL, p = 0.001). Interestingly, a statistically significant positive correlation was observed between vitamin D serum levels and PaO2 (p = 0.03), SO2 (p = 0.05), PaO2/FiO2 (p = 0.02), while a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p = 0.04), C-reactive protein (p = 0.04) and percentage of O2 in a venturi mask (p = 0.04). A negative correlation was also observed between vitamin D serum levels and severity of radiologic pulmonary involvement, evaluated by computed tomography: in particular, vitamin D was found significantly lower in COVID-19 patients with either multiple lung consolidations (p = 0.0001) or diffuse/severe interstitial lung involvement than in those with mild involvement (p = 0.05). Finally, significantly lower vitamin D serum levels were found in the elderly COVID-19 patients who died during hospitalization, compared to those who survived (median 3.0 vs 8.4 ng/mL, p = 0.046). Conclusions: This study confirms that 25OH-vitamin D serum deficiency is associated with more severe lung involvement, longer disease duration and risk of death, in elderly COVID-19 patients. The detection of low vitamin D levels also in younger COVID-19 patients with less comorbidities further suggests vitamin D deficiency as crucial risk factor at any age.

scholarly journals What is the clinical course of patients hospitalised for COVID-19 treatment Ireland: a retrospective cohort study in Dublin’s North Inner City (the ‘Mater 100’)

2020 ◽  
Vol 3 ◽  
pp. 80
Author(s):  
Brendan O’Kelly ◽  
Colm Cronin ◽  
Stephen Peter Connolly ◽  
Walter Cullen ◽  
Gordana Avramovic ◽  
...  
Keyword(s):  
Intensive Care ◽  
Clinical Characteristics ◽  
Laboratory Data ◽  
Supplemental Oxygen ◽  
University Hospital ◽  
Initial Assessment ◽  
Hospital Treatment ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
D Dimer

Background: Ireland has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While several cohorts from China have been described, there is little data describing the epidemiological and clinical characteristics of Irish patients with COVID-19. To improve our understanding of this infection we performed a retrospective review of patient data to examine the clinical characteristics of patients admitted for COVID-19 hospital treatment. Methods: Demographic, clinical and laboratory data on the first 100 patients admitted to Mater Misericordiae University Hospital for in-patient COVID-19 treatment after onset of the outbreak in March 2020 was extracted from patient records. Results: The median age was 45 years (interquartile range [IQR] =34-64 years), 58% were male, and 63% were Irish nationals. Patients had symptoms for a median of five days before diagnosis (IQR=2.5-7 days), most commonly cough (72%), fever (65%), dyspnoea (37%), fatigue (28%), myalgia (27%) and headache (24%). Of all cases, 54 had at least one pre-existing chronic illness (most commonly hypertension, diabetes mellitus or asthma). At initial assessment, the most common abnormal findings were: C-reactive protein >7.0mg/L (74%), ferritin >247μg/L (women) or >275μg/L (men) (62%), D-dimer >0.5μg/dL (62%), chest imaging (59%), NEWS Score (modified) of ≥3 (55%) and heart rate >90/min (51%). Supplemental oxygen was required by 27 patients, of which 17 were admitted to the intensive care unit - 14 requiring ventilation. Antiviral therapy was administered to 40 patients (most commonly hydroxychloroquine or lopinavir/ritonavir). Four died, 17 were admitted to intensive care, and 74 were discharged home, with nine days the median hospital stay (IQR=6-11). Conclusion: Our findings reinforce the consensus of COVID-19 as an acute life-threatening disease and highlights the importance of laboratory (ferritin, C-reactive protein, D-dimer) and radiological parameters, in addition to clinical parameters. Further cohort studies followed longitudinally are a priority.

scholarly journals Cerebrovascular comorbidity, high blood levels of C - reactive protein and D-dimer are associated with disease outcomes in COVID-19 patients

2020 ◽  
pp. 1-12
Author(s):  
Foad Alzoughool ◽  
Lo’ai Alanagreh ◽  
Suhad Abumweis ◽  
Manar Atoum
Keyword(s):  
Case Reports ◽  
Meta Analysis ◽  
Serum Levels ◽  
Blood Levels ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Cerebrovascular Complications ◽  
Increased Risk ◽  
Risk Of Disease ◽  
D Dimer

The emerging coronavirus disease (COVID-19) swept the world, affecting more than 200 countries and territories. As of August 22, 2020, the pandemic infected more than 23,329,752 including 807,054 patients who have died. Although the main clinical features of the pandemic disease are respiratory, cerebrovascular comorbidities emerged as one of the leading causes of death associated with COVID-19. Different case reports have indicated that C-reactive protein (CRP) and D-dimer (pro-inflammatory biomarkers) were elevated in COVID-19 patients, which can significantly increase the risk of ischemic stroke. Available data on cerebrovascular complications in COVID-19 patients were collected and a meta-analysis was designed and carried out to evaluate the risk of severity and mortality associated with high levels of CRP and D-dimer levels in COVID-19 patients. In addition, we aimed to describe the overall event rate of pre-existing cerebrovascular disease in COVID-19 patients. In our analysis, 5,614 cases have been studied, out of these patients 164 cases have developed cerebrovascular comorbities. Cerebrovascular comorbidity increased the risk of disease severity (odd ratio = 4.4; 95% CI: 1.48 to 12.84) and mortality (odd ratio = 7.0; 95% CI: 2.56 to 18.99). Statistical analyses showed that CRP and D-dimer serum levels were elevated by six-folds in the severe cases of COVID-19 patients. This significant increase in these two proteins levels can serve as a vital indicator for COVID-19 patients who are at increased risk of severe COVID-19 cerebrovascular complications, such as stroke.

scholarly journals Beneficial effects of colchicine for moderate to severe COVID-19: an interim analysis of a randomized, double-blinded, placebo controlled clinical trial

2020 ◽  
Author(s):  
Maria Isabel F Lopes ◽  
Leticia P Bonjorno ◽  
Marcela C Giannini ◽  
Natalia B Amaral ◽  
Maira N Benatti ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Placebo Group ◽  
Adverse Events ◽  
Interim Analysis ◽  
Supplemental Oxygen ◽  
Serum Lactate Dehydrogenase ◽  
Controlled Clinical Trial ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Double Blinded

Introduction. Neutrophilia and high levels of proinflammatory cytokines and other mediators of inflammation are common finds in patients with severe acute respiratory syndrome due to COVID-19, a dramatic condition for which there is no specific treatment, but supportive care and attempts to control the systemic inflammation. By its action on leukocytes, we propose colchicine as an intervention worthy of being tested. Objective. To evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes. Methods. We present the interim analysis of a single-center randomized, double-blinded, placebo controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 38 patients allocated 1:1 from April 11 to July 06, 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The first dose was 1.0 mg whether body weight was ≥ 80 kg. Endpoints. The primary endpoints were the need for supplemental oxygen; time of hospitalization; need for admission and length of stay in intensive care unit; and death rate and causes of mortality. As secondary endpoints, we assessed: serum C-reactive protein, serum Lactate dehydrogenase and relation neutrophil to lymphocyte of peripheral blood samples from day zero to day 7; the number, type, and severity of adverse events; frequency of interruption of the study protocol due to adverse events; and frequency of QT interval above 450 ms. Results. Thirty-five patients (18 for Placebo and 17 for Colchicine) completed the study. Both groups were comparable in terms of demographic, clinical and laboratory data at baseline. Median (and interquartile range) time of need for supplemental oxygen was 3.0 (1.5-6.5) days for the Colchicine group and 7.0 (3.0-8.5) days for Placebo group (p = 0.02). Median (IQR) time of hospitalization was 6.0 (4.0-8.5) days for the Colchicine group and 8.5 (5.5-11.0) days for Placebo group (p = 0.03). At day 2, 53% vs 83% of patients maintained the need for supplemental oxygen, while at day 7 the values were 6% vs 39%, in the Colchicine and Placebo groups, respectively (log rank; p = 0.01). Hospitalization was maintained for 53% vs 78% of patients at day 5 and 6% vs 17% at day 10, for the Colchicine and Placebo groups, respectively (log rank; p = 0.01). One patient per group needed admission to ICU. No recruited patient died. At day 4, patients of Colchicine group presented significant reduction of serum C-reactive protein compared to baseline (p < 0.001). The majority of adverse events were mild and did not lead to patient withdrawal. Diarrhea was more frequent in the Colchicine group (p = 0.17). Cardiac adverse events were absent. Discussion. The use of colchicine reduced the length of both, supplemental oxygen therapy and hospitalization. Shortly less than half of the patients of the Colchicine group stopped receiving supplemental oxygen until day 2. Clinical improvement was in parallel with a reduction on serum levels of C-reactive protein. The drug was safe and well tolerated. Colchicine may be considered a beneficial and not expensive option for COVID-19 treatment. Clinical trials with larger numbers of patients should be conducted to further evaluate the efficacy and safety of colchicine as an adjunctive therapy for hospitalized patients with moderate to severe COVID-19.

scholarly journals Efficiency of il-6 inhibitor (olokizumab) in suppressing inflammation in patients with moderate COVID-19 pneumonia

2020 ◽  
Vol 5 (4) ◽  
pp. 8-13
Author(s):  
N. G. Ganyukova ◽  
M. I. Likstanov ◽  
M. V. Kosinova ◽  
I. N. Kushnir ◽  
V. G. Moses ◽  
...  
Keyword(s):  
Placebo Group ◽  
Treatment Group ◽  
Blood Cell ◽  
Cell Count ◽  
Treatment Outcomes ◽  
Lymphocyte Count ◽  
C Reactive Protein ◽  
Blood Cell Count ◽  
Reactive Protein ◽  
D Dimer

Aim. To study the efficiency of IL-6 inhibitor olokizumab in suppressing the inflammation and improving treatment outcomes in patients with moderate COVID-19 pneumonia. Materials and Methods. We enrolled 48 patients with confirmed COVID-19 pneumonia who had indications for the treatment with olokizumab. Treatment group (n = 29) included patients who received a single subcutaneous injection of olokizumab (0.4 mL, 160 mg/mL) while placebo group (n = 19) included those who did not receive the drug because of contraindications. Inflammatory markers (C-reactive protein, white blood cell count, lymphocyte count, ferritin and D-dimer) have been evaluated on the 1st and the 5th day after the administration of olokizumab. Efficiency of olokizumab was assessed by the treatment outcome and suppression of cytokine storm. Results. At the 5th day, SpO2 was 90% (88; 92-93) in both groups, yet none of the patients in the treatment group required a mechanical ventilation, in contrast to 21.1% patients in the placebo group (p = 0.001). Inflammatory parameters were also reduced in the treatment group according to the measurements of serum C-reactive protein (5.6 (1.8;13.5) and 23 (17;92.5) mg/L in the treatment and placebo group, respectively, p = 0.0002) and white blood cell count (5.9 (4.8;6.2) and 7.6 (6.6;12 )*109 /L in the treatment and placebo group, respectively, p=0.03). No statistically significant differences were registered regarding serum ferritin (325 (200; 700) and 215 (186; 526) ng/mL, p = 0.41), D-dimer (827 (378; 1940) and 1464 (677; 4600) ng FEU/mL, p = 0.16) and lymphocyte count (1.3 (0.8; 2.1) and 1.5 (1; 2.1)*109 /L, p =0.44). Death was registered in 3.5% and 21.1% of patients in the treatment and placebo group, respectively, (p = 0.05). Conclusion. Olokizumab ameliorated the progression of COVID-19 pneumonia, improved treatment outcomes and reduced systemic inflammation.

scholarly journals Effect of Corticosteroids on C-Reactive Protein in Patients with Severe Community-Acquired Pneumonia and High Inflammatory Response: The Effect of Lymphopenia

2019 ◽  
Vol 8 (9) ◽  
pp. 1461 ◽  
Author(s):  
Torres ◽  
Ceccato ◽  
Ferrer ◽  
Gabarrus ◽  
Sibila ◽  
...  
Keyword(s):  
Placebo Group ◽  
Inflammatory Response ◽  
Lymphocyte Count ◽  
Controlled Trial ◽  
Community Acquired Pneumonia ◽  
C Reactive Protein ◽  
Post Hoc Analysis ◽  
Reactive Protein ◽  
Inflammatory Status ◽  
Post Hoc

Background: Lymphopenic patients with community-acquired pneumonia (CAP) have shown high mortality rates. Corticosteroids have immunomodulatory properties and regulate cytokine storm in CAP. However, it is not known whether their modulatory effect on cytokine secretion differs in lymphopenic and non-lymphopenic patients with CAP. Therefore, we aimed to test whether the presence of lymphopenia may modify the response to corticosteroids (mainly in C reactive protein (CRP)) in patients with severe CAP and high inflammatory status). Methods: A post hoc analysis of a randomized controlled trial [1] (NCT00908713) which evaluated the effect of corticosteroids in patients with severe CAP and high inflammatory response (CRP > 15 mg/dL). Patients were clustered according to the presence of lymphopenia (lymphocyte count below 1000 cell/mm3). Results: At day 1, 35 patients (59%) in the placebo group presented with lymphopenia, compared to 44 patients (73%) in the corticosteroid group. The adjusted mean changes from day 1 showed an increase of 1.19 natural logarithm (ln) cell/mm3 in the corticosteroid group and an increase of 0.67 ln cell/mm3 in the placebo group (LS mean difference of the changes in ln (methylprednisolone minus placebo) 0.51, 95%CI (0.02 to 1.01), p = 0.043). A significant effect was also found for the interaction (p = 0.043) between corticosteroids and lymphopenia in CRP values at day 3, with lower values in patients without lymphopenia receiving corticosteroids after adjustments for potential confounders. Conclusion: In this exploratory post hoc analysis from ramdomized controlled trial (RCT) data, the response to corticosteroids, measured by CRP, may differ according to lymphocyte count. Further larger studies are needed to confirm this data.

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