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2.
Thromb Haemost ; 2022 Mar 04.
Article in English | MEDLINE | ID: covidwho-1730360

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2)-related pneumonia is associated with venous and arterial thrombosis . Aim of the study was to find-out a new score for predicting thrombosis in patients with SARS-CoV-2. METHODS: We included a cohort of 674 patients affected by SARS-CoV-2, not requiring intensive care units, and followed-up during the hospitalization until discharge. Routinary analyses performed at in-hospital admission included also serum albumin and D-dimer while arterial and venous thromboses were the end-points of the study. RESULTS: During the follow-up thrombotic events 110 were registered; patients with thrombotic events were older and had lower albumin and higher D-dimer, compared to thrombotic event-free ones. On multivariable logistic regression with step by stepwise procedure age, serum albumin, D-dimer, were independently associated with thrombotic events. The linear combination of age, D-dimer, albumin allowed to build-up the ADA score, whose AUC was 0.752 (95% CI, 0.708-0.795). ADA score was internally validated by bootstrap sampling procedure giving an AUC of 0.752 (95% CI: 0.708 - 0.794). CONCLUSIONS: Combination of age, D-dimer, albumin in the ADA score allows identifying SARS-CoV-2 patients at higher risk of thrombotic events.

3.
Clin Transl Gastroenterol ; 13(1): e00448, 2022 01 13.
Article in English | MEDLINE | ID: covidwho-1726955
4.
Thromb Haemost ; 122(2): 257-266, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1592074

ABSTRACT

BACKGROUND: It is still unclear if patients with community-acquired pneumonia (CAP) and coronavirus disease 2019 (COVID-19) have different rate, typology, and impact of thrombosis on survival. METHODS: In this multicenter observational cohort study, 1,138 patients, hospitalized for CAP (n = 559) or COVID-19 (n = 579) from seven clinical centers in Italy, were included in the study. Consecutive adult patients (age ≥ 18 years) with confirmed COVID-19-related pneumonia, with or without mechanical ventilation, hospitalized from March 1, 2020 to April 30, 2020, were enrolled. COVID-19 was diagnosed based on the World Health Organization interim guidance. Patients were followed-up until discharge or in-hospital death, registering the occurrence of thrombotic events including ischemic/embolic events. RESULTS: During the in-hospital stay, 11.4% of CAP and 15.5% of COVID-19 patients experienced thrombotic events (p = 0.046). In CAP patients all the events were arterial thromboses, while in COVID-19 patients 8.3% were venous and 7.2% arterial thromboses.During the in-hospital follow-up, 3% of CAP patients and 17% of COVID-19 patients died (p < 0.001). The highest mortality rate was found among COVID-19 patients with thrombotic events (47.6 vs. 13.4% in thrombotic-event-free patients; p < 0.001). In CAP, 13.8% of patients experiencing thrombotic events died versus 1.8% of thrombotic event-free ones (p < 0.001). A multivariable Cox-regression analysis confirmed a higher risk of death in COVID-19 patients with thrombotic events (hazard ratio: 2.1; 95% confidence interval: 1.4-3.3; p < 0.001). CONCLUSION: Compared with CAP, COVID-19 is characterized by a higher burden of thrombotic events, different thrombosis typology and higher risk of thrombosis-related in-hospital mortality.


Subject(s)
COVID-19/epidemiology , Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , SARS-CoV-2/physiology , Thrombosis/epidemiology , Aged , COVID-19/mortality , Cohort Studies , Community-Acquired Infections/mortality , Female , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Pneumonia/mortality , Risk Factors , Survival Analysis , Thrombosis/mortality
5.
Kardiol Pol ; 79(11): 1197-1205, 2021.
Article in English | MEDLINE | ID: covidwho-1543158

ABSTRACT

COVID-19 is a viral respiratory illness caused by the SARS-CoV-2 infection. In addition to lung disease, clinical complications of COVID-19 include myocardial damage and ischemia-related vascular disease. Severe manifestations and poor prognosis in these patients are associated with a hypercoagulable state predisposing to thrombotic-related complications and eventually death. However, these clinical features can also occur in other forms of pneumonia, such as community-acquired pneumonia (CAP), which, is also complicated by vascular diseases and characterized by platelet activation. Platelets play a pivotal role in these settings as bacteria and viruses may induce activation via Toll-like receptors (TLRs) in CAP patients and different and multiple pathways, including ACE2-AngII axis and/or TLRs, in COVID-19 patients. Despite evidence confirming the implication of platelet activation in both settings, their contribution to the thrombotic process is still under investigation. Thus, in this review, we (1) compare the thrombotic features of SARS-CoV-2 infection and CAP, (2) analyze the putative mechanisms accounting for venous and arterial thrombosis in SARS-CoV-2 infection, and (3) discuss the potential anticoagulant armamentarium to counteract thrombosis.


Subject(s)
COVID-19 , Thrombosis , Anticoagulants , Blood Platelets , Humans , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/etiology
6.
Eur Heart J Suppl ; 23(Suppl E): E184-E188, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1470144

ABSTRACT

Acute infections may be complicated by thrombosis occurring in the venous and arterial circulation. This may be observed in patients with community-acquired pneumonia (CAP) and also in patients with coronavirus 2019 (COVID-19), that is a pandemic characterized by severe acute respiratory syndrome (SARS-CoV-2) needing mechanical ventilation and intensive care unit treatment. However, the type and rate of thrombosis can vary according to the cause of pneumonia as is more frequently complicated by arterial thrombosis in CAP, while an equal incidence of venous and arterial thrombosis occurs in SARS-CoV-2. The mechanisms of disease are overall platelet-related in CAP while activation of both platelets and clotting system is implicated in the pathogenesis of thrombosis in SARS-CoV-2; this finding could imply a different therapeutic approach of the two settings. Thrombosis may also occur in subjects vaccinated against SARS-CoV-2 even if its incidence is not so high (1/100 000); this rare effect occurs more prevalently in young women, is independent from known risk factors of thrombosis, is caused by antibodies against platelet PF4 and is counteracted by treatment with immunoglobulin and glucocorticoids.

7.
Intern Emerg Med ; 16(5): 1231-1237, 2021 08.
Article in English | MEDLINE | ID: covidwho-1293431

ABSTRACT

BACKGROUND: Patients with coronavirus disease 2019 (Covid-19) may experience venous thrombosis while data regarding arterial thrombosis are sparse. METHODS: Prospective multicenter study in 5 hospitals including 373 patients with Covid-19-related pneumonia. Demographic data, laboratory findings including coagulation tests and comorbidities were reported. During the follow-up any arterial or venous thrombotic events and death were registered. RESULTS: Among 373 patients, 75 (20%) had a thrombotic event and 75 (20%) died. Thrombotic events included 41 venous thromboembolism and 34 arterial thrombosis. Age, cardiovascular disease, intensive care unit treatment, white blood cells, D-dimer, albumin and troponin blood levels were associated with thrombotic events. In a multivariable regression logistic model, intensive care unit treatment (Odds Ratio [OR]: 6.0; 95% Confidence Interval [CI] 2.8-12.6; p < 0.001); coronary artery disease (OR: 2.4; 95% CI 1.4-5.0; p = 0.022); and albumin levels (OR: 0.49; 95% CI 0.28-0.87; p = 0.014) were associated with ischemic events. Age, sex, chronic obstructive pulmonary disease, diabetes, heart failure, coronary heart disease, intensive care unit treatment, in-hospital thrombotic events, D-dimer, C-reactive protein, troponin, and albumin levels were associated with mortality. A multivariable Cox regression analysis showed that in-hospital thrombotic events (hazard ratio [HR]: 2.72; 95% CI 1.59-4.65; p < 0.001), age (HR: 1.035; 95% CI 1.014-1.057; p = 0.001), and albumin (HR: 0.447; 95% CI 0.277-0.723; p = 0.001) predicted morality. CONCLUSIONS: Covid-19 patients experience an equipollent rate of venous and arterial thrombotic events, that are associated with poor survival. Early identification and appropriate treatment of Covid-19 patients at risk of thrombosis may improve prognosis.


Subject(s)
COVID-19/complications , Coronary Artery Disease/etiology , Mortality/trends , Thromboembolism/etiology , Aged , Aged, 80 and over , C-Reactive Protein/analysis , COVID-19/epidemiology , Coronary Artery Disease/epidemiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Odds Ratio , Proportional Hazards Models , Prospective Studies , Thromboembolism/epidemiology
8.
Clin Transl Gastroenterol ; 12(6): e00348, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1259760

ABSTRACT

INTRODUCTION: Patients with community-acquired pneumonia display enhanced levels of lipopolysaccharides (LPS) compared with controls, suggesting that low-grade endotoxemia may be implicated in vascular disturbances. It is unknown whether this occurs in patients with coronavirus 2019 (COVID-19) and its impact on thrombotic complications. METHODS: We measured serum levels of zonulin, a marker of gut permeability, LPS, and D-dimer in 81 patients with COVID-19 and 81 healthy subjects; the occurrence of thrombotic events in COVID-19 during the intrahospital stay was registered. RESULTS: Serum LPS and zonulin were higher in patients with COVID-19 than in control subjects and, in COVID-19, significantly correlated (R = 0.513; P < 0.001). Among the 81 patients with COVID-19, 11 (14%) experienced thrombotic events in the arterial (n = 5) and venous circulation (n = 6) during a median follow-up of 18 days (interquartile range 11-27 days). A logistic regression analysis showed that LPS (P = 0.024) and D-dimer (P = 0.041) independently predicted thrombotic events. DISCUSSION: The study reports that low-grade endotoxemia is detectable in patients with COVID-19 and is associated with thrombotic events. The coexistence of low-grade endotoxemia with enhanced levels of zonulin may suggest enhanced gut permeability as an underlying mechanism.


Subject(s)
COVID-19 , Endotoxemia , Haptoglobins/metabolism , Intestinal Mucosa , Protein Precursors/metabolism , SARS-CoV-2 , Thrombosis , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , Correlation of Data , Endotoxemia/diagnosis , Endotoxemia/metabolism , Endotoxemia/virology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/virology , Lipopolysaccharides/analysis , Male , Middle Aged , Permeability , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/etiology
9.
Platelets ; 32(8): 1009-1017, 2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1258665

ABSTRACT

Platelets may be a target of bacteria and viruses, which can directly or indirectly activate them so promoting thrombosis. In accordance with this, community-acquired pneumonia (CAP) is complicated by ischemia-related vascular disease (myocardial infarction and stroke) in roughly 10% of patients while the incidence of venous thrombosis is uncertain. In CAP platelet biosynthesis of TxA2 is augmented and associated with myocardial infarction; however, a cause-effect relationship is still unclear as unclear is if platelet activation promotes thrombosis or functional changes of coronary tree such vasospasm. Retrospective studies suggested a potential role of aspirin in reducing mortality but the impact on vascular disease is still unknown. Coronavirus disease 2019 (Covid-19) is complicated by thrombosis in roughly 20% of patients with an almost equivalent localization in arterial and venous circulation. Platelet activation seems to have a pivot role in the thrombotic process in Covid-19 as consistently evidenced by its involvement in promoting Tissue Factor up-regulation via leucocyte interaction. Until now, antiplatelet treatment has been scarcely considered for the treatment of Covid-19; interventional trials, however, are in progress to explore this issue. The aim of this review is 1) to compare the type of vascular diseases complicating CAP and Covid-19 2) to assess the different role of platelets in both diseases and 3) to discuss if antiplatelet treatment is potentially useful to improve clinical outcomes.


Subject(s)
Aspirin/therapeutic use , Blood Platelets/metabolism , COVID-19 , Myocardial Infarction , SARS-CoV-2/metabolism , Stroke , Thrombosis , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/mortality , Humans , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Myocardial Infarction/mortality , Stroke/drug therapy , Stroke/metabolism , Stroke/mortality , Thrombosis/drug therapy , Thrombosis/metabolism , Thrombosis/mortality
11.
Eur J Clin Invest ; 50(10): e13378, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-695540

ABSTRACT

BACKGROUND: To systematically review clinical and biochemical characteristics associated with the severity of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19). MATERIALS AND METHODS: Systematic review of observational studies from PubMed, ISI Web of Science, SCOPUS and Cochrane databases including people affected by COVID-19 and reporting data according to the severity of the disease. Data were combined with odds ratio (OR) and metanalysed. Severe COVID-19 was defined by acute respiratory distress syndrome, intensive care unit admission and death. RESULTS: We included 12 studies with 2794 patients, of whom 596 (21.33%) had severe disease. A slightly higher age was found in severe vs non-severe disease. We found that prevalent cerebrovascular disease (odds ratio [OR] 3.66, 95% confidence interval [CI] 1.73-7.72), chronic obstructive pulmonary disease (OR: 2.39, 95% CI 1.10-5.19), prevalent cardiovascular disease (OR: 2.84, 95% CI 1.59-5.10), diabetes (OR: 2.78, 95% CI 2.09-3.72), hypertension (OR: 2.24, 95% CI 1.63-3.08), smoking (OR: 1.54, 95% CI 1.07-2.22) and male sex (OR: 1.22, 95% CI 1.01-1.49) were associated with severe disease. Furthermore, increased procalcitonin (OR: 8.21, 95% CI 4.48-15.07), increased D-Dimer (OR: 5.67, 95% CI 1.45-22.16) and thrombocytopenia (OR: 3.61, 95% CI 2.62-4.97) predicted severe infection. CONCLUSION: Characteristics associated with the severity of SARS-CoV-2 infection may allow an early identification and management of patients with poor outcomes.


Subject(s)
Cardiovascular Diseases/epidemiology , Coronavirus Infections/metabolism , Diabetes Mellitus/epidemiology , Fibrin Fibrinogen Degradation Products/metabolism , Pneumonia, Viral/metabolism , Procalcitonin/metabolism , Pulmonary Disease, Chronic Obstructive/epidemiology , Smoking/epidemiology , Thrombocytopenia/epidemiology , Betacoronavirus , COVID-19 , Cerebrovascular Disorders/epidemiology , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Humans , Hypertension/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Prevalence , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors
12.
Redox Biol ; 36: 101655, 2020 09.
Article in English | MEDLINE | ID: covidwho-671830

ABSTRACT

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.


Subject(s)
Coronavirus Infections/metabolism , NADPH Oxidase 2/metabolism , Pneumonia, Viral/metabolism , Thrombosis/blood , Aged , Biomarkers/blood , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/pathology , Female , Humans , Male , Middle Aged , NADPH Oxidase 2/chemistry , Oxidative Stress , Pandemics , Peptide Fragments/blood , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , Thrombosis/etiology
13.
Drugs ; 80(14): 1383-1396, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-669901

ABSTRACT

Severe Acute Respiratory Syndrome-Coronavirus-2 is responsible for the current pandemic that has led to more than 10 million confirmed cases of Coronavirus Disease-19 (COVID-19) and over 500,000 deaths worldwide (4 July 2020). Virus-mediated injury to multiple organs, mainly the respiratory tract, activation of immune response with the release of pro-inflammatory cytokines, and overactivation of the coagulation cascade and platelet aggregation leading to micro- and macrovascular thrombosis are the main pathological features of COVID-19. Empirical multidrug therapeutic approaches to treat COVID-19 are currently used with extremely uncertain outcomes, and many others are being tested in clinical trials. Acetylsalicylic acid (ASA) has both anti-inflammatory and antithrombotic effects. In addition, a significant ASA-mediated antiviral activity against DNA and RNA viruses, including different human coronaviruses, has been documented. The use of ASA in patients with different types of infections has been associated with reduced thrombo-inflammation and lower rates of clinical complications and in-hospital mortality. However, safety issues related both to the risk of bleeding and to that of developing rare but serious liver and brain damage mostly among children (i.e., Reye's syndrome) should be considered. Hence, whether ASA might be a safe and reasonable therapeutic candidate to be tested in clinical trials involving adults with COVID-19 deserves further attention. In this review we provide a critical appraisal of current evidence on the anti-inflammatory, antithrombotic, and antiviral effects of ASA, from both a pre-clinical and a clinical perspective. In addition, the potential benefits and risks of use of ASA have been put in the context of the adult-restricted COVID-19 population.


Subject(s)
Aspirin/pharmacology , Betacoronavirus , Blood Coagulation , Coronavirus Infections , Inflammation , Pandemics , Pneumonia, Viral , Anti-Inflammatory Agents/pharmacology , Betacoronavirus/drug effects , Betacoronavirus/physiology , Blood Coagulation/drug effects , Blood Coagulation/immunology , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Humans , Inflammation/blood , Inflammation/drug therapy , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Risk Assessment , SARS-CoV-2 , Treatment Outcome
14.
Antioxid Redox Signal ; 35(2): 139-142, 2021 07 10.
Article in English | MEDLINE | ID: covidwho-593682

ABSTRACT

Coronavirus 2019 (COVID-19) is a pandemic associated with a high risk of mortality. Human serum albumin (HSA) is an acute phase reactant with antioxidant property; however, its behavior and impact on survival in COVID-19 patients have never been studied so far. Among 319 COVID-19 patients followed up for a median of 19 days, 64 died. Compared with survivors, nonsurvivors had more prevalence of intensive care unit (ICU) admission, chronic obstructive pulmonary disease (COPD), heart failure, elevated levels of D-dimer, high-sensitivity C reactive protein (hs-CRP) and troponins, and lower values of albumin. At the Cox regression analysis, albumin (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.23-0.63, p < 0.001) and age (HR: 1.03, 95% CI: 1.01-1.06, p = 0.001) were independently associated with mortality, irrespective of adjustment for gender, ICU admission, heart failure, COPD, and hs-CRP levels. Our observation leads to the hypothesis that HSA analysis may be used to identify patients at higher risk of death in COVID-19 patients.

16.
Intern Emerg Med ; 15(5): 755-758, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-245085

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be complicated by myocardial injury but at-risk patients as well as mechanism of disease are unclear. We gathered data regarding troponin levels in the so far reported SARS-CoV-2 patients and found a large variability in terms of troponin levels, patients with more severe disease, as those treated by ICU, presenting with higher percentage of troponin elevation. However, lack of prospective studies hampers adequate analysis of risk factors of myocardial damage. Previous study demonstrated that Nox2 is up-regulated in pneumonia and closely associated with troponin elevation suggesting Nox2 activation as mechanism eliciting myocardial damage; data in SARS-CoV-2 are still lacking. We hypothesize that SARS-Cov-2 may induce myocardial injury via Nox2-related ROS production and that analysis and eventually targeting Nox2 may be a novel approach to manage SARS-CoV-2.


Subject(s)
Coronavirus Infections/complications , Heart Diseases/virology , Pneumonia, Viral/complications , Betacoronavirus , Biomarkers/blood , COVID-19 , Heart Diseases/blood , Humans , Pandemics , Prognosis , SARS-CoV-2 , Troponin/blood
17.
Thromb Haemost ; 120(6): 949-956, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-151374

ABSTRACT

The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number of patients needing mechanical ventilation or intensive care units treatment and for the elevated mortality risk. A link between COVID-19 and multiorgan failure may be dependent on the fact that most COVID-19 patients are complicated by pneumonia, which is known to be associated with early changes of clotting and platelet activation and artery dysfunction; these changes may implicate in thrombotic-related events such as myocardial infarction and ischemic stroke. Recent data showed that myocardial injury compatible with coronary ischemia may be detectable in SARS-CoV-2 patients and laboratory data exploring clotting system suggest the presence of a hypercoagulation state. Thus, we performed a systematic review of COVID-19 literature reporting measures of clotting activation to assess if changes are detectable in this setting and their relationship with clinical severity. Furthermore, we discussed the biologic plausibility of the thrombotic risk in SARS-CoV-2 and the potential use of an antithrombotic treatment.


Subject(s)
Coronavirus Infections/complications , Fibrinolytic Agents/therapeutic use , Pneumonia, Viral/complications , Thrombophilia/prevention & control , Thrombophilia/therapy , Thrombosis/prevention & control , Thrombosis/therapy , Algorithms , Betacoronavirus , COVID-19 , Cardiology , Coronavirus Infections/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Liver Failure/therapy , Pandemics , Partial Thromboplastin Time , Platelet Count , Pneumonia, Viral/blood , Prothrombin Time , Risk , SARS-CoV-2 , Treatment Outcome
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