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1.
Clin Appl Thromb Hemost ; 27: 10760296211010973, 2021.
Article in English | MEDLINE | ID: covidwho-1582642

ABSTRACT

SARS-CoV-2 in COVID-19 triggers abnormalities in coagulation parameters that can contribute to thrombosis. The goals of this research were to determine the levels of fibrinogen, D-dimer and FDP in COVID-19 patients. Following a systematic study, among 1198 articles, 35 studies were included in the meta-analysis of fibrinogen levels in both severe and non-severe groups. The funnel plot, Egger's regression asymmetry test, and Begg's test used to measure the bias of publications. All meta-analysis performed by comprehensive meta-analysis version 2 (CMA2). The pooled findings of fibrinogen levels revealed a significant rise in fibrinogen levels in severe COVID-19 than non-severe patients with COVID-19. The D-dimer and FDP levels were significantly higher in severe patients than non-severe patients with COVID-19 were. The levels of fibrinogen, D-dimer, and FDP have increased significantly in ICU patients compared to non-ICU patients. Although, levels of clotting parameters do not always correlate with the severity of disease, these findings showed the diagnostic importance for fibrinogen, D-dimer, and FDP in COVID-19. The presence of a continuous rise in serial measurements of fibrinogen, D-dimer, and FDP may predict that patients with COVID-19 may become critically ill.


Subject(s)
COVID-19/blood , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Hemostasis , SARS-CoV-2 , Biomarkers , COVID-19/complications , Critical Illness , Humans , Prognosis , Severity of Illness Index , Thrombophilia/blood , Thrombophilia/etiology
2.
Blood Coagul Fibrinolysis ; 32(8): 544-549, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1526211

ABSTRACT

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) (P ≤ 0.003 for all). The presence of high TEG-6 s 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 (P ≤ 0.001 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) = 2.9, P = 0.03], diabetes (OR = 3.3, P = 0.02) and FCS > 40 mm (OR = 3.4, P = 0.02). 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 , African Americans/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 , /statistics & numerical data
3.
J Thromb Thrombolysis ; 53(3): 646-662, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1439746

ABSTRACT

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 µg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.


Subject(s)
COVID-19 , Hemostatics , Thrombophilia , Thrombosis , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , Factor VIII , Fibrinogen/analysis , Humans , Prospective Studies , Thrombelastography , Thrombophilia/diagnosis , Thrombophilia/etiology , Thrombosis/drug therapy , Venous Thromboembolism/drug therapy , von Willebrand Factor
4.
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
5.
Int J Lab Hematol ; 43 Suppl 1: 36-42, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1319316

ABSTRACT

The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.


Subject(s)
Blood Coagulation Tests , COVID-19/blood , SARS-CoV-2 , Thrombophilia/etiology , Antibodies, Antiphospholipid/blood , Biomarkers/blood , Blood Coagulation Factors/analysis , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Factor Xa/analysis , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Fibrinolysis , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Partial Thromboplastin Time , Platelet Count , Prothrombin Time , Thrombelastography , Thrombin/biosynthesis , Thrombophilia/blood , Thrombophilia/drug therapy
6.
J Thromb Thrombolysis ; 53(1): 118-122, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1310601

ABSTRACT

Coronavirus disease (COVID-19)-related systemic cytokine response induces the production of procoagulant factors, which predisposes patients to a prothrombotic state. Viscoelastic testing can identify the degree of hypercoagulability, which is related to outcomes. We aimed to study the changes in clot waveform analysis (CWA) parameters in COVID-19 patients on hospital admission compared to those in a group of healthy individuals. We conducted a retrospective study of COVID-19 patients admitted to general wards and evaluated demographic and clinical parameters as well as laboratory parameters, including coagulation parameters. CWA data from patients (n = 62) with COVID-19 prior to the initiation of anticoagulation therapy were compared with those from healthy controls (n = 67). The measured CWA parameters were min1, min2, max2, and delta change. CWA, fibrinogen, and D-dimer values were higher in COVID-19 patients than in healthy controls (p < 0.001). CWA profiles were consistent with hypercoagulability and characterized by an increase in density, velocity, and acceleration of clot formation. Activated partial thromboplastin time, fibrinogen, D-dimer, and C-reactive protein (CRP) values were higher in patients in whom all CWA parameters were raised than in patients with just a few elevated CWA parameters, while Sequential Organ Failure Assessment scores, prothrombin time, fibrin degradation product levels and platelet counts did not differ between the two groups. CWA variables showed hypercoagulopathy on admission in COVID-19 patients who were hospitalized in the general ward, and this pattern was more pronounced in critically ill patients with elevated fibrinogen, D-dimer, and CRP levels. Our results may help identify patients at high risk of thromboembolism.


Subject(s)
COVID-19 , Thrombophilia , Thrombosis , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/diagnosis , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Retrospective Studies , Thrombophilia/diagnosis
7.
J Infect Dev Ctries ; 15(6): 787-790, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1304765

ABSTRACT

INTRODUCTION: COVID-19 pandemic affects mental health globally. Reports showed the increase of mental illness as a response to the COVID-19 pandemic. However, the correlation between the COVID-19 and mental illness is not fully understood yet. METHODOLOGY: We reported a brief psychotic disorder in a COVID-19 patient with no history of mental illness who was hospitalized in Persahabatan Hospital, Jakarta, Indonesia. RESULTS: Psychotic symptoms appeared five days after COVID-19 onset and laboratory tests showed elevated levels of d-dimer and fibrinogen. CONCLUSIONS: Elevated levels of d-dimer and fibrinogen suggest an ongoing COVID-19-associated coagulopathy that might cause a microdamage in the central nervous system. It might contribute to the manifestation of psychotic symptoms. The correlation between brief psychotic disorder and COVID-19 requires further investigation.


Subject(s)
COVID-19/complications , Psychotic Disorders/virology , Acute Disease , COVID-19/blood , COVID-19/diagnostic imaging , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Indonesia , Male , Middle Aged , Psychotic Disorders/blood , Psychotic Disorders/diagnosis , Radiography , Thorax/diagnostic imaging , Thorax/virology
8.
Int J Gynaecol Obstet ; 154(2): 297-303, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1298486

ABSTRACT

OBJECTIVE: To evaluate the effect of the coronavirus disease 2019 (COVID-19) mask-wearing on hematological laboratory components and obstetrical outcomes among women delivering during the COVID-19 pandemic. METHODS: Laboratory results and obstetrical outcomes of women with singleton gestations, admitted for delivery during the COVID-19 mask-wearing period (April-June 2020) were compared with those of women delivering during the parallel period in 2019 and with a larger cohort derived from nine pre-pandemic years (March 2011-April 2020). RESULTS: Overall, 1838 women delivered during the COVID-19 pandemic. Compared with the pre-pandemic period, mean hemoglobin and fibrinogen levels were significantly higher during the mask-wearing period (12.15 ± 1.1 vs 11.96 ± 1.2, P < 0.001 and 472 ± 103.6 vs 448 ± 85.1 mg/dl, P < 0.001, respectively). Platelet levels were lower (200 ± 56.0 vs 206 ± 57.5 K/µl, P < 0.001). The rate of delivery at <34 weeks of gestation was lower during the mask-wearing period (1.1% vs 2%, odds ratio [OR] 0.57, 95% confidence intervals [CI] 0.37-0.88, P = 0.01), whereas cesarean delivery and postpartum hemorrhage rates were higher (26.7% vs 24.4%, OR 1.13, 95% CI 1.02-1.25, P = 0.022 and 4.1% vs 2.8%, OR 1.5, 95% CI 1.2-1.8, P = 0.001, respectively). CONCLUSION: A hard-to-ventilate space created by wearing a mask during the COVID-19 era may be the underlying cause of the observed higher hemoglobin level among pregnant women, possibly affecting obstetrical outcomes.


Subject(s)
COVID-19/prevention & control , Cesarean Section/statistics & numerical data , Masks , Pregnant Women/psychology , Term Birth , Adult , Blood Platelets , COVID-19/epidemiology , Cohort Studies , Female , Fibrinogen/analysis , Hemoglobins/analysis , Hospitalization , Humans , Pandemics , Pregnancy , SARS-CoV-2
9.
Sci Rep ; 11(1): 12716, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1275959

ABSTRACT

Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring upon massive monocyte activation, has recently emerged as promising early biomarker of sepsis. Similar to sepsis, monocyte/macrophage subsets are considered key mediators of the life-threatening hyper-inflammatory disorder characterizing severe COVID-19. In this study, we longitudinally analyzed MDW values in a cohort of 87 COVID-19 patients consecutively admitted to our hospital, showing significant correlations between MDW and common inflammatory markers, namely CRP (p < 0.001), fibrinogen (p < 0.001) and ferritin (p < 0.01). Moreover, high MDW values resulted to be prognostically associated with fatal outcome in COVID-19 patients (AUC = 0.76, 95% CI: 0.66-0.87, sensitivity 0.75, specificity 0.70, MDW threshold 26.4; RR = 4.91, 95% CI: 1.73-13.96; OR = 7.14, 95% CI: 2.06-24.71). This pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is: (1) easy to obtain, (2) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (3) well correlated with clinical severity of COVID-19-associated inflammatory disorder, and, in turn, (4) endowed with relevant prognostic significance. Additional studies are needed to define further the clinical impact of MDW testing in the management of COVID-19 patients.


Subject(s)
COVID-19/blood , Cell Size , Monocytes/pathology , SARS-CoV-2 , Severity of Illness Index , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/epidemiology , COVID-19/virology , Female , Ferritins/blood , Fibrinogen/analysis , Humans , Inflammation/blood , Italy/epidemiology , Longitudinal Studies , Male , Middle Aged , Patient Admission , Pilot Projects , Prognosis , Retrospective Studies , Sensitivity and Specificity , Young Adult
10.
N Engl J Med ; 385(8): 720-728, 2021 08 19.
Article in English | MEDLINE | ID: covidwho-1262030

ABSTRACT

The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. At the time of this report, Canada had restricted the use of the ChAdOx1 nCoV-19 vaccine to persons who were 55 years of age or older on the basis of reports that VITT had occurred primarily in younger persons. Two of the patients in our study presented with limb-artery thrombosis; the third had cerebral venous and arterial thrombosis. Variable patterns of serum-induced platelet activation were observed in response to heparin and platelet factor 4 (PF4), indicating the heterogeneity of the manifestations of VITT in serum. After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients. (Funded by the Canadian Institutes of Health Research.).


Subject(s)
COVID-19 Vaccines/adverse effects , Immunoglobulins, Intravenous , Thrombocytopenia/therapy , Thrombosis/therapy , Aged , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Heparin/pharmacology , Humans , Male , Middle Aged , Platelet Count , Platelet Factor 4/pharmacology , Serotonin/blood , Thrombocytopenia/blood , Thrombocytopenia/etiology , Thrombosis/etiology , Thrombosis/immunology
11.
PLoS One ; 16(5): e0249964, 2021.
Article in English | MEDLINE | ID: covidwho-1232459

ABSTRACT

Coronavirus disease 2019 (COVID-19) is highly contagious and has affected the whole world. We seek to investigate the clinical and laboratory characteristics of COVID-19 patients in the high altitude areas of Sichuan, China. In this retrospective cohort study, a total of 67 patients with laboratory-confirmed SARS-CoV-2 infections in Sichuan's Ngawa Tibetan and Qiang Autonomous Prefecture were included from February 1, 2020, to March 2, 2020. Their clinical characteristics, as well as radiological and laboratory features, were extracted. Four (6.0%) patients were categorized as severe cases; 39 (58.2%) were non-severe cases, and 24 (35.8%) were asymptomatic cases. A total of 46 (68.7%) patients were associated with cluster infection events in this study. The most common symptoms were cough, sputum production, dyspnea, fatigue or myalgia, and headache. Seven (10.4%) patients showed leucopenia, and 20 (29.9%) patients showed lymphopenia. Lymphocyte counts and neutrophil-to-lymphocyte ratios (NPR) were different between the three groups. In total, 14 (20.9%) patients had thrombocytopenia, and prothrombin times (PT) and fibrinogen levels differed between groups. We also found significant differences in sodium, chloride and calcium levels between the three groups. Antiviral therapy did not lead to obvious adverse events or shortened durations from initial positive to subsequent negative nuclei acid tests. Advanced age, hypertension, high neutrophil count, the neutrophil-to-lymphocyte ratio, fibrinogen and lactate dehydrogenase levels were identified as independent risk factors for symptomatic cases of COVID-19. In conclusion, the symptoms of patients in high altitude areas were mild, and about one third were asymptomatic. We also identified several independent risk factors for symptomatic cases of COVID-19.


Subject(s)
COVID-19/pathology , Adolescent , Adult , Aged , Altitude , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Cough/etiology , Female , Fibrinogen/analysis , Humans , L-Lactate Dehydrogenase/metabolism , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Young Adult
12.
J Hepatol ; 75(3): 647-658, 2021 09.
Article in English | MEDLINE | ID: covidwho-1228069

ABSTRACT

BACKGROUND AND AIMS: COVID-19 is associated with liver injury and elevated interleukin-6 (IL-6). We hypothesized that IL-6 trans-signaling in liver sinusoidal endothelial cells (LSECs) leads to endotheliopathy (a proinflammatory and procoagulant state) and liver injury in COVID-19. METHODS: Coagulopathy, endotheliopathy, and alanine aminotransferase (ALT) were retrospectively analyzed in a subset (n = 68), followed by a larger cohort (n = 3,780) of patients with COVID-19. Liver histology from 43 patients with COVID-19 was analyzed for endotheliopathy and its relationship to liver injury. Primary human LSECs were used to establish the IL-6 trans-signaling mechanism. RESULTS: Factor VIII, fibrinogen, D-dimer, von Willebrand factor (vWF) activity/antigen (biomarkers of coagulopathy/endotheliopathy) were significantly elevated in patients with COVID-19 and liver injury (elevated ALT). IL-6 positively correlated with vWF antigen (p = 0.02), factor VIII activity (p = 0.02), and D-dimer (p <0.0001). On liver histology, patients with COVID-19 and elevated ALT had significantly increased vWF and platelet staining, supporting a link between liver injury, coagulopathy, and endotheliopathy. Intralobular neutrophils positively correlated with platelet (p <0.0001) and vWF (p <0.01) staining, and IL-6 levels positively correlated with vWF staining (p <0.01). IL-6 trans-signaling leads to increased expression of procoagulant (factor VIII, vWF) and proinflammatory factors, increased cell surface vWF (p <0.01), and increased platelet attachment in LSECs. These effects were blocked by soluble glycoprotein 130 (IL-6 trans-signaling inhibitor), the JAK inhibitor ruxolitinib, and STAT1/3 small-interfering RNA knockdown. Hepatocyte fibrinogen expression was increased by the supernatant of LSECs subjected to IL-6 trans-signaling. CONCLUSION: IL-6 trans-signaling drives the coagulopathy and hepatic endotheliopathy associated with COVID-19 and could be a possible mechanism behind liver injury in these patients. LAY SUMMARY: Patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection often have liver injury, but why this occurs remains unknown. High levels of interleukin-6 (IL-6) and its circulating receptor, which form a complex to induce inflammatory signals, have been observed in patients with COVID-19. This paper demonstrates that the IL-6 signaling complex causes harmful changes to liver sinusoidal endothelial cells and may promote blood clotting and contribute to liver injury.


Subject(s)
COVID-19/complications , Endothelial Cells/pathology , Interleukin-6/physiology , Liver Diseases/etiology , SARS-CoV-2 , Adult , Blood Coagulation Disorders/etiology , Fibrinogen/analysis , Humans , Interleukin-6/blood , Janus Kinase 1/metabolism , Nitriles , Pyrazoles/pharmacology , Pyrimidines , Retrospective Studies , STAT3 Transcription Factor/metabolism , Signal Transduction/physiology , von Willebrand Factor/analysis
13.
Int J Lab Hematol ; 43(5): 1243-1251, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1211529

ABSTRACT

INTRODUCTION: Although factors such as age, sex, diabetes, obesity and changes in certain laboratory investigations are important prognostic factors in COVID-19 infection, these may not apply to all ethnic/racial groups. We hypothesized differences in routine biochemistry and haematology indices in Caucasian and a combined group of Black, Asian and Minority Ethnic (BAME) patients who tested positive for COVID-19 who died, compared to survivors. METHODS: We tested our hypothesis in 445 patients (229 Caucasian, 216 BAME) admitted to secondary care with proven COVID-19 infection, in whom standard routine laboratory indices were collected on admission. RESULTS: After 28 weeks, 190 (42.7%) had died within 28 days of COVID diagnosis (97 Caucasians [42.4%], 93 BAMEs [43.1%], P = .923). A general linear model analysis found the ethnicity interaction with mortality to be significant for fibrinogen, ferritin and HbA1 c (after controlling for age). In a multivariate analysis, a neutrophil/lymphocyte ratio > 7.4 and a urea/albumin ratio > 0.28 increased the odds of death for both the Caucasian and the BAME group. Additional factors increasing the odds ratio in the BAME group included age >60 years and being diabetic. CONCLUSION: Neutrophil/lymphocyte ratio and urea/albumin ratio are simple metrics that predict death to aid clinicians in determining the prognosis of COVID-19 and help provide early intensive intervention to reduce mortality. In the BAME groups, intensive monitoring even at younger age and those with diabetes may also help reduce COVID-19 associated mortality.


Subject(s)
COVID-19/blood , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Ferritins/analysis , Fibrinogen/analysis , Glycated Hemoglobin A/analysis , Humans , Leukocyte Count , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Serum Albumin, Human/analysis , Urea/blood
14.
J Med Virol ; 93(2): 934-944, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196422

ABSTRACT

The outbreak of 2019 novel coronavirus disease (COVID-19) has posed a grave threat to the global public health. The COVID-19-induced infection is closely related to coagulation dysfunction in the affected patients. This paper attempts to conduct a meta-analysis and systematically review the blood coagulation indicators in patients with severe COVID-19. A meta-analysis of eligible studies was performed to compare the blood coagulation indicators in patients with severe and nonsevere COVID-19. PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published between 1 December 2019 and 7 May 2020. A total of 13 studies with 1341 adult patients were enrolled in this analysis. Platelet (weighted mean difference [WMD] = -24.83, 95% confidence interval [CI]: -34.12 to -15.54; P < .001), d-dimer (WMD = 0.19, 95% CI: 0.09-0.29; P < .001), and fibrinogen (WMD = 1.02, 95% CI: 0.50-1.54; P < .001) were significantly associated with the severity in patients with COVID-19. The meta-analysis revealed that no correlation was evident between an increased severity risk of COVID-19 and activated partial thromboplastin time (WMD = -1.56, 95% CI: -5.77 to 2.64; P = .468) or prothrombin time (WMD = 0.19, 95% CI: -0.13 to 0.51; P = .243). The single arm meta-analysis showed that compared with the nonsevere group, the severe group had a lower pooled platelet (165.12 [95% CI: 157.38-172.85] vs 190.09 [95% CI: 179.45-200.74]), higher d-dimer (0.49 [95% CI: 0.33-0.64] vs 0.27 [95% CI: 0.20-0.34]), and higher fibrinogen (4.34 [95% CI: 1.98-6.70] vs 3.19 [95% CI: 1.13-5.24]). Coagulation dysfunction is closely related to the severity of patients with COVID-19, in which low platelet, high d-dimer, and fibrinogen upon admission may serve as risk indicators for increased aggression of the disease. These findings are of great clinical value for timely and effective treatment of the COVID-19 cases.


Subject(s)
Blood Coagulation Disorders/virology , COVID-19/complications , Blood Platelets , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Hospitalization , Humans , Partial Thromboplastin Time , Prognosis , Risk Factors , Severity of Illness Index
15.
J Med Virol ; 93(2): 962-972, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196416

ABSTRACT

To systematically analyze the blood coagulation features of coronavirus disease 2019 (COVID-19) patients to provide a reference for clinical practice. An electronic search in PubMed, EMbase, Web of Science, Scopus, CNKI, WanFang Data, and VIP databases to identify studies describing the blood coagulation features of COVID-19 patients from 1 January 2020 to 21 April 2020. Three reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies, then, the meta-analysis was performed by using Stata 12.0 software. Thirty-four studies involving 6492 COVID-19 patients were included. Meta-analysis showed that patients with severe disease showed significantly lower platelet count (weighted mean differences [WMD]: -16.29 × 109 /L; 95% confidence interval [CI]: -25.34 to -7.23) and shorter activated partial thromboplastin time (WMD: -0.81 seconds; 95% CI: -1.94 to 0.33) but higher D-dimer levels (WMD: 0.44 µg/mL; 95% CI: 0.29-0.58), higher fibrinogen levels (WMD: 0.51 g/L; 95% CI: 0.33-0.69) and longer prothrombin time (PT; WMD: 0.65 seconds; 95% CI: 0.44-0.86). Patients who died showed significantly higher D-dimer levels (WMD: 6.58 µg/mL; 95% CI: 3.59-9.57), longer PT (WMD: 1.27 seconds; 95% CI: 0.49-2.06) and lower platelet count (WMD: -39.73 × 109 /L; 95% CI: -61.99 to -17.45) than patients who survived. Coagulation dysfunction is common in severe COVID-19 patients and it is associated with severity of COVID-19.


Subject(s)
Blood Coagulation Disorders/virology , COVID-19/complications , COVID-19/mortality , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Leukocyte Count , Platelet Count , Prothrombin Time , Risk Factors
16.
J Med Virol ; 93(3): 1761-1765, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196476

ABSTRACT

To determine the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viral loads (VL) during the acute phase of infection and their correlation with clinical presentation and inflammation-related biomarkers. Nasopharyngeal swabs from 453 adult SARS-CoV-2-infected patients from the Department of Infectious Diseases, Besançon, France, were collected at the time of admission or consultation for reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Clinical information and concentrations of biological parameters (C-reactive protein [CRP], fibrinogen, lactate dehydrogenase [LDH], prealbumin) were noticed. Mean respiratory VL homogeneously decreased from 7.2 log10 copies/ml (95% confidence interval [CI]: 6.6-7.8) on the first day of symptoms until 4.6 log10 copies/ml (95% CI: 3.8-5.4) at day 10 (slope = -0.24; R2 = .95). VL were poorly correlated with COVID-19 symptoms and outcome, excepted for dyspnea and anosmia, which were significantly associated with lower VL (p < .05). CRP, fibrinogen, and LDH concentrations significantly increased over the first 10 days (median CRP concentrations from 36.8 mg/L at days 0-1 to 99.5 mg/L at days 8-10; p < .01), whereas prealbumin concentrations tended to decrease. Since SARS-CoV-2 respiratory VL regularly decrease in the acute phase of infection, determining the level of VL may help predicting the onset of virus shedding in a specific patient. However, the role of SARS-CoV-2 VL as a biomarker of severity is limited.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/epidemiology , Viral Load/methods , Adult , Aged , Aged, 80 and over , Anosmia/pathology , C-Reactive Protein/analysis , Dyspnea/pathology , Female , Fibrinogen/analysis , France/epidemiology , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Nasopharynx/virology , Prealbumin/analysis , RNA, Viral/analysis , SARS-CoV-2 , Treatment Outcome , Virus Shedding , Young Adult
17.
J Thromb Thrombolysis ; 52(2): 497-503, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1188149

ABSTRACT

The coronavirus disease 2019 (COVID-19) increases thrombotic risk. The mechanisms that lead to this prothrombotic state are not well established. The main aim was to evaluate the von Willebrand factor (VWF) antigen and plasma ADAMTS13 activity as endothelial injury markers in COVID-19. We present a prospective study in COVID-19 patients recruited in our institution. VWF antigen, ADAMTS13 activity, D-dimer, and fibrinogen were measured during the first week once COVID-19 was diagnosed. Fifty COVID-19 inpatients [44% in the intensive care unit (ICU)] and 102 COVID-19 outpatients were enrolled. Thirty age and gender matched non-COVID-19 ward inpatients and 30 non-COVID-19 healthy individuals were recruited. The COVID-19 inpatients had higher D-dimer, fibrinogen, and VWF antigen levels and a lower ADAMTS13 activity compared with the COVID-19 outpatients (p < 0.05). ICU patients had higher D-dimer and VWF antigen levels compared with the ward patients and the lowest ADAMTS13 activity (p < 0.05). An imbalance in VWF antigen/ADAMTS13 ratio was observed in COVID-19, reaching the highest in ICU patients. In contrast to other ward non-COVID-19 inpatients, a significative reduction in ADAMTS13 activity was observed in all COVID-19 patients. There is an increase in VWF antigen and an ADAMTS13 activity reduction in COVID-19 related to disease severity and could predict poor clinical outcomes. The ADAMTS13 activity reduction could be a marker associated with COVID-19 compared to other non-critical medical conditions.


Subject(s)
ADAMTS13 Protein/blood , COVID-19 , Endothelium, Vascular , Risk Assessment , Thrombophilia , von Willebrand Factor/analysis , Aged , Ambulatory Care/statistics & numerical data , Biomarkers/analysis , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , Correlation of Data , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Prospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spain/epidemiology , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/virology
18.
J Med Virol ; 93(7): 4559-4563, 2021 07.
Article in English | MEDLINE | ID: covidwho-1162848

ABSTRACT

Coronavirus disease 2019 (COVID-19) is globally rampant, and to curb the growing burden of this disease, in-depth knowledge about its pathophysiology is needed. This was an observational study conducted at a single center to investigate serum cytokine and chemokine levels of COVID-19 patients, based on disease severity. We included 72 consecutive COVID-19 patients admitted to our hospital from March 21 to August 31, 2020. Patients were divided into Mild-Moderate I (mild) and Moderate II-Severe (severe) groups based on the COVID-19 severity classification developed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. We compared the patient characteristics as well as the serum cytokine and chemokine levels on the day of admission between the two groups. Our findings indicated that the severe group had significantly higher levels of serum fibrinogen, d-dimer, lactate dehydrogenase, C-reactive protein, ferritin, Krebs von den Lungen-6, surfactant protein (SP)-D, and SP-A than the mild group. Strikingly, the levels of interleukin (IL)-28A/interferon (IFN)-λ2 were significantly lower in the severe group than in the mild group. We believe that reduced levels of type III interferons (IFN-λs) and alterations in the levels of other cytokines and chemokines may impact the severity of the disease.


Subject(s)
COVID-19/blood , Chemokines/blood , Interferons/blood , SARS-CoV-2/immunology , Adult , Aged , C-Reactive Protein/analysis , COVID-19/pathology , Down-Regulation , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Interferons/biosynthesis , Interleukins/blood , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Mucin-1/blood , Pulmonary Surfactant-Associated Protein A/blood , Pulmonary Surfactant-Associated Protein D/blood , Severity of Illness Index
19.
Clin Appl Thromb Hemost ; 27: 1076029621996445, 2021.
Article in English | MEDLINE | ID: covidwho-1148196

ABSTRACT

BACKGROUND: To investigate the factors associated with elevated fibrinogen (Fbg) levels in COVID-19 patients with and without diabetes (DM) and impaired fasting glucose (IFG). METHODS: According to whether or not their glucose metabolism was impaired, COVID-19 patients were subdivided into 2 groups: 1) with DM and IFG, 2) control group. Their demographic data, medical history, signs and symptoms, laboratory results, and final clinical results were analyzed retrospectively. RESULTS: 28 patients (16.3%) died during hospitalization, including 21 (29.2%) in group 1 and 7 (7.0%) in group 2 (P < 0.001). Fbg levels in groups 1 and 2 were higher than the normal range, at 5.6 g/L (IQR 4.5-7.2 g/L) and 5.0 g/L (IQR 4.0-6.1 g/L), respectively (P = 0.009). Serum ferritin levels, C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), triglycerides (TG) were significantly increased in group 1 compared to those in the control. TG levels were 1.3 mmol/L in the control, while that in group 1 was 1.8 mmol/L. Multiple linear regression showed that the predicting factors of Fbg in the control group were serum ferritin and CRP, R2 = 0.295; in group 1, serum ferritin, CRP, and TG, R2 = 0.473. CONCLUSIONS: Fbg in all COVID-19 patients is related to serum ferritin and CRP involved in inflammation. Furthermore, in COVID-19 patients with insulin resistance, Fbg is linearly positively correlated with TG. This suggests that regulation of TG, insulin resistance, and inflammation may reduce hypercoagulability in COVID-19 patients, especially those with insulin resistance.


Subject(s)
Blood Glucose/analysis , COVID-19/blood , Diabetes Mellitus/blood , Fasting/blood , Fibrinogen/analysis , Insulin Resistance , Thrombophilia/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Coagulation , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/virology , Diabetes Mellitus/diagnosis , Female , Ferritins/blood , Humans , Inflammation Mediators/blood , Male , Middle Aged , Retrospective Studies , Thrombophilia/diagnosis , Thrombophilia/virology , Triglycerides/blood , Up-Regulation , Young Adult
20.
J Med Virol ; 93(7): 4358-4369, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1141369

ABSTRACT

To conduct a systematic review and meta-analysis to characterize inflammatory markers in comparisons of multisystem inflammatory syndrome in children (MIS-C) versus severe/non-severe COVID-19, severe MIS-C versus non-severe MIS-C, and among age groups of MIS-C. Nine databases were searched for studies on inflammatory markers of MIS-C. After quality checks, data were pooled using a fixed or random effects model. Inflammatory markers included white blood cell count (WBC) or leukocytes, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), ferritin, D-dimer, lactate dehydrogenase (LDH), fibrinogen, and erythrocyte sedimentation rate (ESR) for comparisons by severity and age. Twenty-one studies with 1735 participants yielded 787 MIS-C patients. Compared to non-severe COVID-19 patients, MIS-C patients had lower ALC and higher ANC, CRP, and D-dimer levels. Compared to severe COVID-19 patients, MIS-C patients had lower LDH and PLT counts and higher ESR levels. Severe MIS-C patients had higher levels of WBC, ANC, CRP, D-dimer, and ferritin than non-severe MIS-C patients. For MIS-C, younger children (0-5 years) had lower CRP and ferritin levels than middle-aged/older children/adolescents. Measurement of inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS-C and the associated disorders.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Biomarkers/analysis , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/pathology , Child , Child, Preschool , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Infant , Infant, Newborn , L-Lactate Dehydrogenase/blood , Leukocyte Count , Lymphocyte Count , Lymphocytes/cytology , Neutrophils/cytology , Platelet Count , Procalcitonin/blood , Systemic Inflammatory Response Syndrome/pathology , Young Adult
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