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2.
PLoS One ; 16(10): e0258351, 2021.
Article in English | MEDLINE | ID: covidwho-1496507

ABSTRACT

BACKGROUND: Elevated D-dimer is known as predictor for severity of SARS-CoV2-infection. Increased D-dimer is associated with thromboembolic complications, but it is also a direct consequence of the acute lung injury seen in COVID-19 pneumonia. OBJECTIVES: To evaluate the rate of persistent elevated D-dimer and its association with thromboembolic complications and persistent ground glass opacities (GGO) after recovery from COVID-19. METHODS: In this post hoc analysis of a prospective multicenter trial, patients underwent blood sampling, measurement of diffusion capacity, blood gas analysis, and multidetector computed tomography (MDCT) scan following COVID-19. In case of increased D-dimer (>0,5 µg/ml), an additional contrast medium-enhanced CT was performed in absence of contraindications. Results were compared between patients with persistent D-dimer elevation and patients with normal D-dimer level. RESULTS: 129 patients (median age 48.8 years; range 19-91 years) underwent D-Dimer assessment after a median (IQR) of 94 days (64-130) following COVID-19. D-dimer elevation was found in 15% (19/129) and was significantly more common in patients who had experienced a severe SARS-CoV2 infection that had required hospitalisation compared to patients with mild disease (p = 0.049). Contrast-medium CT (n = 15) revealed an acute pulmonary embolism in one patient and CTEPH in another patient. A significant lower mean pO2 (p = 0.015) and AaDO2 (p = 0.043) were observed in patients with persistent D-Dimer elevation, but the rate of GGO were similar in both patient groups (p = 0.33). CONCLUSION: In 15% of the patients recovered from COVID-19, persistent D-dimer elevation was observed after a median of 3 months following COVID-19. These patients had experienced a more severe COVID and still presented more frequently a lower mean pO2 and AaDO2.


Subject(s)
COVID-19/metabolism , Fibrin Fibrinogen Degradation Products/analysis , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Middle Aged , Prospective Studies , Pulmonary Embolism/prevention & control , RNA, Viral , Retrospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index , Tomography, X-Ray Computed/methods
3.
Eur Rev Med Pharmacol Sci ; 25(19): 5889-5903, 2021 10.
Article in English | MEDLINE | ID: covidwho-1478931

ABSTRACT

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.


Subject(s)
COVID-19/blood , COVID-19/mortality , Estradiol/blood , Inflammation/blood , Inflammation/etiology , Testosterone/blood , Vitamin D/analogs & derivatives , Adult , Aged , Aged, 80 and over , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Hospitalization , Humans , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Procalcitonin/blood , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Analysis , Vitamin D/blood
4.
J Infect Dev Ctries ; 15(9): 1236-1243, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1478144

ABSTRACT

INTRODUCTION: The study aims to identify potential risk factors for the poor outcome of hospitalized patients with SARS-CoV-2 infection in Albania. METHODOLOGY: A retrospective observational study on 133 consecutive hospitalized patients at "COVID 1" Hospital, University Hospital Center of Tirana. The study analyzed the correlation between potential risk factors and in-hospital mortality. RESULTS: The study included 133 patients, 65.4% of the patients were male, age 60.46 ± 13.53 years. The mortality rate resulted in 22.6%. Univariate analysis revealed that early risk factors for mortality included: laboratory alterations on admission, such as lymphocytes count < 1.000/mm3 (OR = 3.30, 95% CI = 1.17-9.33), lactate dehydrogenase > 250 U/L (OR = 12.48, 95% CI = 1.62-95.78) and D dimer > 2 mg/L (OR = 4.72, 95% CI = 1.96-11.36); lung parenchymal involvement > 75% on chest computed tomography on admission (OR = 54.00, 95% CI = 11.89 - 245.11). Cox proportional hazard regression showed that independent risk factors for mortality were lung parenchymal involvement > 75% on chest computed tomography (HR = 8.31, 95%CI: 1.62-42.45) and occurrence of complications during hospital stay (OR = 10.28, 95% CI = 2.02-52.33). CONCLUSIONS: The risk of poor outcome can be predicted from the early stage of COVID 19 disease, using laboratory data and chest computed tomography. Among patients with COVID 19, lung parenchymal involvement and alterations > 75% on chest computed tomography on admission and laboratory findings, such as lymphocytopenia, and elevated lactate dehydrogenase and D dimer levels, turned out to be early risk factors for in-hospital mortality.


Subject(s)
COVID-19/epidemiology , Hospital Mortality , Adult , Aged , Aged, 80 and over , Albania/epidemiology , COVID-19/mortality , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , L-Lactate Dehydrogenase/blood , Lung/pathology , Male , Middle Aged , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed
5.
Sci Rep ; 11(1): 19728, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1454814

ABSTRACT

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , C-Reactive Protein/analysis , COVID-19/mortality , COVID-19/pathology , Dose-Response Relationship, Drug , Fibrin Fibrinogen Degradation Products/analysis , Humans , Odds Ratio , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survival Analysis , Survival Rate
6.
Clin Appl Thromb Hemost ; 27: 10760296211039288, 2021.
Article in English | MEDLINE | ID: covidwho-1448131

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a systemic disease that can be life-threatening involving immune and inflammatory responses, and that can result in potentially lethal complications, including venous thrombo-embolism (VTE). Forming an integrative approach to thrombo-prophylaxis and coagulation treatment for COVID-19 patients ensues. We aim at reviewing the literature for anticoagulation in the setting of COVID-19 infection to provide a summary on anticoagulation for this patient population. COVID-19 infection is associated with a state of continuous inflammation, which results in macrophage activation syndrome and an increased rate of thrombosis. Risk assessment models to predict the risk of thrombosis in critically ill patients have not yet been validated. Currently published guidelines suggest the use of prophylactic intensity over intermediate intensity or therapeutic intensity anticoagulant for patients with critical illness or acute illness related to COVID-19 infection. Critically ill COVID-19 patients who are diagnosed with acute VTE are considered to have a provoking factor, and, therefore, treatment duration should be at least 3 months. Patients with proximal deep venous thrombosis or pulmonary embolism should receive parenteral over oral anticoagulants with low-molecular-weight heparin or fondaparinux preferred over unfractionated heparin. In patients with impending hemodynamic compromise due to PE, and who are not at increased risk for bleeding, reperfusion may be necessary. Internists should remain updated on new emerging evidence regarding anticoagulation for COVID-19 patients. Awaiting these findings, we invite internists to perform individualized decisions that are unique for every patient and to base them on clinical judgment for risk assessment.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , SARS-CoV-2 , Thrombophilia/drug therapy , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Consensus , Critical Illness , Disease Management , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Female , Fibrin Fibrinogen Degradation Products/analysis , Fondaparinux/adverse effects , Fondaparinux/therapeutic use , Hemorrhage/chemically induced , Heparin/adverse effects , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inpatients , Male , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Hematologic/prevention & control , Pregnancy Complications, Infectious/blood , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Risk , Thrombophilia/etiology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
7.
Clin Appl Thromb Hemost ; 27: 10760296211045902, 2021.
Article in English | MEDLINE | ID: covidwho-1443743

ABSTRACT

INTRODUCTION: Diabetes is the most common of comorbidity in patients with SARS-COV-2 pneumonia. Coagulation abnormalities with D-dimer levels are increased in this disease. OBJECTIFS: We aimed to compare the levels of D-dimer in diabetic and non-diabetic patients with COVID 19. A link between D-dimer and mortality has also been established. MATERIALS: A retrospective study was carried out at the University Hospital Center of Oujda (Morocco) from November 01st to December 01st, 2020. Our study population was divided into two groups: a diabetic group and a second group without diabetes to compare clinical and biological characteristics between the two groups. In addition, the receiver operator characteristic curve was used to assess the optimal D-dimer cut-off point for predicting mortality in diabetics. RESULTS: 201 confirmed-COVID-19-patients were included in the final analysis. The median age was 64 (IQR 56-73), and 56% were male. Our study found that D-dimer levels were statistically higher in diabetic patients compared to non-diabetic patients. (1745 vs 845 respectively, P = 0001). D-dimer level > 2885 ng/mL was a significant predictor of mortality in diabetic patients with a sensitivity of 71,4% and a specificity of 70,7%. CONCLUSION: Our study found that diabetics with COVID-19 are likely to develop hypercoagulation with a poor prognosis.


Subject(s)
COVID-19/blood , Diabetes Mellitus/blood , Fibrin Fibrinogen Degradation Products/analysis , SARS-CoV-2 , Thrombophilia/blood , Aged , Area Under Curve , Biomarkers , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/epidemiology , Comorbidity , Diabetes Complications/blood , Diabetes Complications/epidemiology , Diabetes Mellitus/epidemiology , Female , Hospital Mortality , Humans , Hypertension/epidemiology , Inflammation/immunology , Kaplan-Meier Estimate , Male , Middle Aged , Oxidative Stress , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , Thrombophilia/etiology , Thrombophilia/immunology
8.
BMC Pregnancy Childbirth ; 21(1): 658, 2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1440917

ABSTRACT

BACKGROUND: Whilst the impact of Covid-19 infection in pregnant women has been examined, there is a scarcity of data on pregnant women in the Middle East. Thus, the aim of this study was to examine the impact of Covid-19 infection on pregnant women in the United Arab Emirates population. METHODS: A case-control study was carried out to compare the clinical course and outcome of pregnancy in 79 pregnant women with Covid-19 and 85 non-pregnant women with Covid-19 admitted to Latifa Hospital in Dubai between March and June 2020. RESULTS: Although Pregnant women presented with fewer symptoms such as fever, cough, sore throat, and shortness of breath compared to non-pregnant women; yet they ran a much more severe course of illness. On admission, 12/79 (15.2%) Vs 2/85 (2.4%) had a chest radiograph score [on a scale 1-6] of ≥3 (p-value = 0.0039). On discharge, 6/79 (7.6%) Vs 1/85 (1.2%) had a score ≥3 (p-value = 0.0438). They also had much higher levels of laboratory indicators of severity with values above reference ranges for C-Reactive Protein [(28 (38.3%) Vs 13 (17.6%)] with p < 0.004; and for D-dimer [32 (50.8%) Vs 3(6%)]; with p < 0.001. They required more ICU admissions: 10/79 (12.6%) Vs 1/85 (1.2%) with p=0.0036; and suffered more complications: 9/79 (11.4%) Vs 1/85 (1.2%) with p=0.0066; of Covid-19 infection, particularly in late pregnancy. CONCLUSIONS: Pregnant women presented with fewer Covid-19 symptoms but ran a much more severe course of illness compared to non-pregnant women with the disease. They had worse chest radiograph scores and much higher levels of laboratory indicators of disease severity. They had more ICU admissions and suffered more complications of Covid-19 infection, such as risk for miscarriage and preterm deliveries. Pregnancy with Covid-19 infection, could, therefore, be categorised as high-risk pregnancy and requires management by an obstetric and medical multidisciplinary team.


Subject(s)
COVID-19 , Intensive Care Units/statistics & numerical data , Pregnancy Complications, Infectious , Premature Birth , Radiography, Thoracic , Symptom Assessment , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/etiology , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , COVID-19/transmission , Case-Control Studies , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Male , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Pregnancy Outcome/epidemiology , Pregnancy, High-Risk , Premature Birth/epidemiology , Premature Birth/etiology , Radiography, Thoracic/methods , Radiography, Thoracic/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , United Arab Emirates/epidemiology
9.
Medicine (Baltimore) ; 100(38): e27216, 2021 Sep 24.
Article in English | MEDLINE | ID: covidwho-1437853

ABSTRACT

ABSTRACT: Deep venous thrombosis (DVT) is associated with high mortality in coronavirus disease 2019 (COVID-19) but there remains uncertainty about the benefit of anti-coagulation prophylaxis and how to decide when ultrasound screening is indicated. We aimed to determine parameters predicting which COVID-19 patients are at risk of DVT and to assess the benefit of prophylactic anti-coagulation.Adult hospitalized patients with positive severe acute respiratory syndrome coronavirus-2 reverse transcription-polymerase chain reaction (RT-PCR) undergoing venous duplex ultrasound for DVT assessment (n = 451) were retrospectively reviewed. Clinical and laboratory data within 72 hours of ultrasound were collected. Using split sampling and a 10-fold cross-validation, a random forest model was developed to find the most important variables for predicting DVT. Different d-dimer cutoffs were examined for classification of DVT. We also compared the rate of DVT between the patients going and not going under thromboprophylaxis.DVT was found in 65 (14%) of 451 reverse transcription-polymerase chain reaction positive patients. The random forest model, trained and cross-validated on 2/3 of the original sample (n = 301), had area under the receiver operating characteristic curve = 0.91 (95% confidence interval [CI]: 0.85-0.97) for prediction of DVT in the test set (n = 150), with sensitivity = 93% (95%CI: 68%-99%) and specificity = 82% (95%CI: 75%-88%). The following variables had the highest importance: d-dimer, thromboprophylaxis, systolic blood pressure, admission to ultrasound interval, and platelets. Thromboprophylaxis reduced DVT risk 4-fold from 26% to 6% (P < .001), while anti-coagulation therapy led to hemorrhagic complications in 14 (22%) of 65 patients with DVT including 2 fatal intra-cranial hemorrhages. D-dimer was the most important predictor with area under curve = 0.79 (95%CI: 0.73-0.86) by itself, and a 5000 ng/mL threshold at 7 days postCOVID-19 symptom onset had 75% (95%CI: 53%-90%) sensitivity and 81% (95%CI: 72%-88%) specificity. In comparison with d-dimer alone, the random forest model showed 68% versus 32% specificity at 95% sensitivity, and 44% versus 23% sensitivity at 95% specificity.D-dimer >5000 ng/mL predicts DVT with high accuracy suggesting regular monitoring with d-dimer in the early stages of COVID-19 may be useful. A random forest model improved the prediction of DVT. Thromboprophylaxis reduced DVT in COVID-19 patients and should be considered in all patients. Full anti-coagulation therapy has a risk of life-threatening hemorrhage.


Subject(s)
Anticoagulants/adverse effects , COVID-19/complications , Fibrin Fibrinogen Degradation Products/analysis , Ultrasonography, Doppler, Duplex/standards , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control , Acute Disease , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , COVID-19 Nucleic Acid Testing/methods , Case-Control Studies , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , ROC Curve , Retrospective Studies , Risk Factors , SARS-CoV-2/genetics , Sensitivity and Specificity , Ultrasonography, Doppler, Duplex/methods , Venous Thrombosis/epidemiology , Venous Thrombosis/mortality
10.
Int Immunopharmacol ; 100: 108127, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401543

ABSTRACT

BACKGROUND: Early detection of oxidant-antioxidant levels and special care in severe patients are important in combating the COVID-19 epidemic. However, this process is costly and time consuming. Therefore, there is a need for faster, reliable and economical methods. METHODS: In this study, antioxidant/oxidant levels of patients were estimated by Expert-models using biomarkers, which are effective in the diagnosis/prognosis of COVID-19 disease. For this purpose, Expert-models were trained and created between the white-blood-cell-count (WBC), lymphocyte-count (LYM), C-reactive-protein (CRP), D-dimer, ferritin values of 35 patients with COVID-19 and antioxidant/oxidant parameter values of the same patients. Error criteria and R2 ratio were taken into account for the performance of the models. The validity of the all models was checked by the Box-Jenkis-method. RESULTS: Antioxidant/Oxidant levels were estimated with 95% confidence-coefficient using the values of WBC, LYM, CRP, D-dimer, ferritin of different 500 patients diagnosed with COVID-19 with the trained models. The error rate of all models was low and the coefficients of determination were sufficient. In the first data set, there was no significant difference between measured antioxidant/oxidant levels and predicted antioxidant/oxidant levels. This result showed that the models are accurate and reliable. In determining antioxidant/oxidant levels, LYM and ferritin biomarkers had the most effect on models, while WBC and CRP biomarkers had the least effect. The antioxidant/oxidant parameter estimated with the highest accuracy was Native-Thiol divided by Total-Thiol. CONCLUSIONS: The results showed that the antioxidant/oxidant levels of infected patients can be estimated accurately and reliably with LYM, ferritin, D-dimer, WBC, CRP biomarkers in the COVID-19 outbreak.


Subject(s)
Antioxidants/analysis , COVID-19/metabolism , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Biomarkers , C-Reactive Protein/analysis , COVID-19/diagnosis , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Leukocyte Count , Male , Middle Aged , Oxidants/metabolism , Prognosis , Retrospective Studies , Young Adult
11.
Hematology ; 26(1): 656-662, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1398020

ABSTRACT

OBJECTIVES: Coagulation dysfunction is an evident factor in the clinical diagnosis and treatment of patients with coronavirus disease 2019 (COVID-19), appearing even in COVID-19 patients with normal inflammation indices. Therefore, this study aimed to analyze the characteristics of coagulation function indices in COVID-19 patients to investigate possible mechanisms through the comparison of non-severe and severe COVID-19 patients. METHODS: We included 143 patients whose clinical characteristics, coagulation function, and other indices such as inflammatory factors were collected and compared based on disease severity. RESULTS: Activated partial thromboplastin time (APTT), D-dimer, and fibrinogen levels were evidently higher in the severe group than in the non-severe group. Among non-severe COVID-19 patients, the aforementioned indicators depicted increasing trends, but the fibrinogen level alone was higher than normal. However, in severe COVID-19 patients, values of all three indices were higher than normal. In severe COVID-19 patients, fibrinogen and D-dimer were correlated with several inflammation indices during the early stage of the disease. However, no correlation between fibrinogen and inflammatory factors was observed in non-severe COVID-19 patients at any time point. DISCUSSION: Results revealed that the hypercoagulability tendency of severe COVID-19 patients was more evident. The relationship between coagulation function and inflammatory factors showed that changes in coagulation function in severe COVID-19 patients may be related to abnormal increase in inflammatory factors at an early stage; however, in non-severe COVID-19 patients, there might be other factors leading to abnormal coagulation. CONCLUSION: Inflammatory factors were not the only cause of abnormal coagulation function in COVID-19 patients.


Subject(s)
Blood Coagulation , COVID-19/blood , Disseminated Intravascular Coagulation/blood , Thrombophilia/blood , Adult , Aged , COVID-19/complications , Disseminated Intravascular Coagulation/etiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Longitudinal Studies , Male , Middle Aged , Partial Thromboplastin Time , Severity of Illness Index , Thrombophilia/etiology
12.
J Cardiovasc Med (Hagerstown) ; 22(11): 832-839, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1394702

ABSTRACT

INTRODUCTION: Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19. METHODS: We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136. RESULTS: Mean age was 69 ±â€Š16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality. CONCLUSION: In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement.


Subject(s)
COVID-19 , Cardiovascular Diseases , Natriuretic Peptides/blood , Troponin/blood , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/mortality , Cardiovascular Diseases/classification , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Comorbidity , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Italy/epidemiology , Male , Outcome Assessment, Health Care , Prognosis , Risk Assessment , Risk Factors , SARS-CoV-2/isolation & purification
14.
Ann R Coll Surg Engl ; 103(8): 604-611, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1379818

ABSTRACT

INTRODUCTION: A novel hyperinflammatory syndrome has emerged in the paediatric population: paediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS). Up to 50% of patients develop shock with cardiac dysfunction but presentation with acute abdominal pain is common and difficult to distinguish from appendicitis. METHOD: Prospective case series of PIMS-TS patients presenting to a single UK tertiary paediatric centre. RESULTS: As of 16 September 2020, 89 patients have presented with PIMS-TS to our institution; 19 (21.3%) were referred for surgical review. Pyrexia and acute abdominal pain were seen in all 19 patients. Diarrhoea was reported in 14 (73%) and vomiting in 12 (63%). On examination, eight (42%) had right abdominal tenderness, of which five had right iliac fossa (RIF) peritonism. C-reactive protein (CRP) was universally raised: median 176 (15-463)mg/l. Abdominal imaging was performed in 17 (89%), with 11 undergoing abdominal ultrasonography (65%) and 8 abdominal computed tomography (47%); two required both. Findings included nonspecific features of inflammation in the RIF. Eight patients (42%) had an abnormal echocardiogram at admission. Two (10%) patients, with classical signs and symptoms of appendicitis, underwent appendicectomy without radiological imaging and were subsequently diagnosed with PIMS-TS. During the same period, 18 patients underwent appendicectomy for histologically confirmed appendicitis. Serum CRP and ferritin levels were significantly higher in the PIMS-TS cohort compared with children with appendicitis. CONCLUSIONS: PIMS-TS is a novel paediatric condition that may mimic appendicitis. It should be considered in patients presenting with abdominal pain to avoid unnecessary surgery in children at risk of cardiovascular instability.


Subject(s)
COVID-19/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Appendectomy , Appendicitis/diagnosis , Appendicitis/surgery , Biomarkers/blood , C-Reactive Protein/analysis , Child , Child, Preschool , Diagnosis, Differential , Female , Ferritins/analysis , Fibrin Fibrinogen Degradation Products/analysis , Humans , Infant , Male , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies
15.
Adv Med Sci ; 66(2): 372-380, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1379020

ABSTRACT

OBJECTIVES: D-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19. METHODS: A literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468). RESULTS: Thirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 â€‹% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 â€‹% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 â€‹% confidence interval, CI 0.42 to 0.77; p â€‹< â€‹0.001). There was extreme between-study heterogeneity (I2 â€‹= â€‹90.2 â€‹%; p â€‹< â€‹0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p â€‹= â€‹0.048) and D-dimer (p â€‹= â€‹0.001). CONCLUSIONS: Prolonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.


Subject(s)
COVID-19 , Fibrin Fibrinogen Degradation Products/analysis , International Normalized Ratio , Thrombophilia , COVID-19/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Humans , International Normalized Ratio/methods , International Normalized Ratio/statistics & numerical data , Mortality , SARS-CoV-2 , Severity of Illness Index , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/etiology
16.
PLoS One ; 16(8): e0256744, 2021.
Article in English | MEDLINE | ID: covidwho-1374154

ABSTRACT

INTRODUCTION: Coronavirus Disease 2019 is a primarily respiratory illness that can cause thrombotic disorders. Elevation of D-dimer is a potential biomarker for poor prognosis in COVID-19, though optimal cutoff value for D-dimer to predict mortality has not yet been established. This study aims to assess the accuracy of admission D-dimer in the prognosis of COVID-19 and to establish the optimal cutoff D-dimer value to predict hospital mortality. METHODS: Clinical and laboratory parameters and outcomes of confirmed COVID-19 cases admitted to four hospitals in Kathmandu were retrospectively analyzed. Admitted COVID-19 cases with recorded D-dimer and definitive outcomes were included consecutively. D-dimer was measured using immunofluorescence assay and reported in Fibrinogen Equivalent Unit (µg/ml). The receiver operating characteristic curve was used to determine the accuracy of D-dimer in predicting mortality, and to calculate the optimal cutoff value, based on which patients were divided into two groups and predictive value of D-dimer for mortality was measured. RESULTS: 182 patients were included in the study out of which 34(18.7%) died during the hospital stay. The mean admission D-dimer among surviving patients was 1.067 µg/ml (±1.705 µg/ml), whereas that among patients who died was 3.208 µg/ml (±2.613 µg/ml). ROC curve for D-dimer and mortality gave an area under the curve of 0.807 (95% CI 0.728-0.886, p<0.001). Optimal cutoff value for D-dimer was 1.5 µg/ml (sensitivity 70.6%, specificity 78.4%). On Cox proportional hazards regression analysis, the unadjusted hazard ratio for high D-dimer was 6.809 (95% CI 3.249-14.268, p<0.001), and 5.862 (95% CI 2.751-12.489, p<0.001) when adjusted for age. CONCLUSION: D-dimer value on admission is an accurate biomarker for predicting mortality in patients with COVID-19. 1.5 µg/ml is the optimal cutoff value of admission D-dimer for predicting mortality in COVID-19 patients.


Subject(s)
Biomarkers/analysis , COVID-19/diagnosis , Fibrin Fibrinogen Degradation Products/analysis , Adult , Aged , Area Under Curve , COVID-19/mortality , COVID-19/virology , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proportional Hazards Models , ROC Curve , Retrospective Studies , SARS-CoV-2/isolation & purification
17.
PLoS One ; 16(8): e0256226, 2021.
Article in English | MEDLINE | ID: covidwho-1374147

ABSTRACT

Coronavirus disease (COVID)-19, as a result of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has been the direct cause of over 2.2 million deaths worldwide. A timely coordinated host-immune response represents the leading driver for restraining SARS-CoV-2 infection. Indeed, several studies have described dysregulated immunity as the crucial determinant for critical illness and the failure of viral control. Improved understanding and management of COVID-19 could greatly reduce the mortality and morbidity caused by SARS-CoV-2. One aspect of the immune response that has to date been understudied is whether lipid mediator production is dysregulated in critically ill patients. In the present study, plasma from COVID-19 patients with either severe disease and those that were critically ill was collected and lipid mediator profiles were determined using liquid chromatography tandem mass spectrometry. Results from these studies indicated that plasma concentrations of both pro-inflammatory and pro-resolving lipid mediator were reduced in critically ill patients when compared with those with severe disease. Furthermore, plasma concentrations of a select group of mediators that included the specialized pro-resolving mediators (SPM) Resolvin (Rv) D1 and RvE4 were diagnostic of disease severity. Interestingly, peripheral blood SPM concentrations were also linked with outcome in critically ill patients, where we observed reduced overall concentrations of these mediators in those patients that did not survive. Together the present findings establish a link between plasma lipid mediators and disease severity in patients with COVID-19 and indicate that plasma SPM concentrations may be linked with survival in these patients.


Subject(s)
COVID-19/diagnosis , Docosahexaenoic Acids/blood , SARS-CoV-2/isolation & purification , Adult , Aged , COVID-19/virology , Chromatography, High Pressure Liquid , Critical Illness , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Male , Middle Aged , Severity of Illness Index , Tandem Mass Spectrometry , Up-Regulation
18.
Diabetes Metab Syndr ; 15(5): 102240, 2021.
Article in English | MEDLINE | ID: covidwho-1347578

ABSTRACT

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.


Subject(s)
COVID-19/diagnosis , Glomerular Filtration Rate/physiology , Plasma/chemistry , Biomarkers/blood , Blood Coagulation/physiology , COVID-19/blood , COVID-19/physiopathology , COVID-19/therapy , Cohort Studies , Diabetes Complications/blood , Diabetes Complications/diagnosis , Diabetes Complications/physiopathology , Diabetes Complications/therapy , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Humans , India , Male , Middle Aged , Osmolar Concentration , Patient Admission/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/etiology , Thrombosis/physiopathology , Water-Electrolyte Balance/physiology
19.
Sci Rep ; 11(1): 16025, 2021 08 06.
Article in English | MEDLINE | ID: covidwho-1345583

ABSTRACT

To determine, in patients with coronavirus disease 2019 (COVID-19) infection, the associations of pulmonary embolism (PE) with mortality and risk factors for PE as well as the therapeutic benefit of anticoagulant prophylaxis. Embase, PubMed, Cochrane controlled trials register, and Web of Science databases were searched from inception to October 10, 2020. We included all published trials on PE in patients diagnosed with COVID-19 with eligibility of the trials assessed following the PRISMA guidelines. Sixteen clinical trials with 5826 patients were eligible. There were significant associations of PE with the male gender [odd ratio (OR) = 1.59, 95% CI 1.28-1.97], mechanical ventilation (OR = 3.71, 95% CI 2.57-5.36), intensive care unit admission (OR = 2.99, 95% CI 2.11-4.23), circulating D-dimer [mean difference (MD) = 5.04 µg/mL, 95% CI 3.67-6.42) and CRP (MD = 1.97 mg/dL, 95% CI 0.58- 3.35) concentrations without significant correlation between PE and mortality (OR = 1.31, 95% CI 0.82-2.08) as well as other parameters or comorbidities. After omitting one trial with strict patient selection criteria for anticoagulant prophylaxis, significant prophylactic benefit was noted (OR = 0.31, 95% CI 0.1-0.91). Our findings identified the risk factors associated with PE in COVID-19 patients and supported the therapeutic benefit of anticoagulant prophylaxis against PE in this patient population.


Subject(s)
COVID-19/complications , Pulmonary Embolism/etiology , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Male , Pulmonary Embolism/blood , Pulmonary Embolism/mortality , Pulmonary Embolism/therapy , Respiration, Artificial , Risk Factors , SARS-CoV-2/isolation & purification , Sex Factors
20.
JAMA ; 326(3): 230-239, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1338164

ABSTRACT

Importance: Effective treatments for patients with severe COVID-19 are needed. Objective: To evaluate the efficacy of canakinumab, an anti-interleukin-1ß antibody, in patients hospitalized with severe COVID-19. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Intervention: Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227). Main Outcomes and Measures: The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Results: Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Conclusions and Relevance: Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT04362813.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Interleukin-1beta/antagonists & inhibitors , Respiration, Artificial/statistics & numerical data , Aged , Antibodies, Monoclonal, Humanized/adverse effects , C-Reactive Protein/analysis , COVID-19/mortality , COVID-19/therapy , Combined Modality Therapy , Double-Blind Method , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Survival Rate , Treatment Outcome
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