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1.
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.

2.
J Thromb Haemost ; 20(4): 961-974, 2022 04.
Article in English | MEDLINE | ID: covidwho-1626860

ABSTRACT

BACKGROUND: A rapid immune response is critical to ensure effective protection against COVID-19. Platelets are first-line sentinels of the vascular system able to rapidly alert and stimulate the immune system. However, their role in the immune response to vaccines is not known. OBJECTIVE: To identify features of the platelet-immune crosstalk that would provide an early readout of vaccine efficacy in adults who received the mRNA-based COVID-19 vaccine (BNT162b2). METHODS: We prospectively enrolled 11 young healthy volunteers (54% females, median age: 28 years) who received two doses of BNT162b2, 21 days apart, and we studied their platelet and immune response before and after each dose of the vaccine (3 and 10 ± 2 days post-injection), in relation to the kinetics of the humoral response. RESULTS: Participants achieving an effective level of neutralizing antibodies before the second dose of the vaccine (fast responders) had a higher leukocyte count, mounted a rapid cytokine response that incremented further after the second dose, and an elevated platelet turnover that ensured platelet count stability. Their circulating platelets were not more reactive but expressed lower surface levels of the immunoreceptor tyrosine-based inhibitory motif (ITIM)-coupled receptor CD31 (PECAM-1) compared to slow responders, and formed specific platelet-leukocyte aggregates, with B cells, just 3 days after the first dose, and with non-classical monocytes and eosinophils. CONCLUSION: We identified features of the platelet-immune crosstalk that are associated with the development of a rapid humoral response to an mRNA-based vaccine (BNT162b2) and that could be exploited as early biomarkers of vaccine efficacy.


Subject(s)
Blood Platelets/immunology , COVID-19 , Immunity, Humoral , Adult , Antibodies, Viral/blood , COVID-19/prevention & control , Female , Humans , Male , SARS-CoV-2
3.
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
4.
Dermatol Ther ; 34(6): e15153, 2021 11.
Article in English | MEDLINE | ID: covidwho-1555455

ABSTRACT

An in-depth characterization of the incidence, morphology, and onset of COVID-19-vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID-19 vaccination-related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID-19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine-related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID-19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID-19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID-19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2
5.
Sci Rep ; 11(1): 17774, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1397896

ABSTRACT

The Coronavirus Disease (COVID-19) pandemic imposed a high burden of morbidity and mortality. In COVID-19, direct lung parenchymal involvement and pulmonary microcirculation dysfunction may entail pulmonary hypertension (PH). PH and direct cardiac injury beget right ventricular dysfunction (RVD) occurrence, which has been frequently reported in COVID-19 patients; however, the prevalence of RVD and its impact on outcomes during COVID-19 are still unclear. This study aims to evaluate the prevalence of RVD and associated outcomes in patients with COVID-19, through a Systematic Review and Meta-Analysis. MEDLINE and EMBASE were systematically searched from inception to 15th July 2021. All studies reporting either the prevalence of RVD in COVID-19 patients or all-cause death according to RVD status were included. The pooled prevalence of RVD and Odds Ratio (OR) for all-cause death according to RVD status were computed and reported. Subgroup analysis and meta-regression were also performed. Among 29 studies (3813 patients) included, pooled prevalence of RVD was 20.4% (95% CI 17.1-24.3%; 95% PI 7.8-43.9%), with a high grade of heterogeneity. No significant differences were found across geographical locations, or according to the risk of bias. Severity of COVID-19 was associated with increased prevalence of RVD at meta-regression. The presence of RVD was found associated with an increased likelihood of all-cause death (OR 3.32, 95% CI 1.94-5.70). RVD was found in 1 out of 5 COVID-19 patients, and was associated with all-cause mortality. RVD may represent one crucial marker for prognostic stratification in COVID-19; further prospective and larger are needed to investigate specific management and therapeutic approach for these patients.


Subject(s)
COVID-19/complications , Hospitalization/statistics & numerical data , Pandemics/statistics & numerical data , Ventricular Dysfunction, Right/epidemiology , COVID-19/mortality , COVID-19/therapy , COVID-19/virology , Cause of Death , Hospital Mortality , Humans , Prevalence , Prognosis , Risk Assessment/statistics & numerical data , Risk Factors , SARS-CoV-2/pathogenicity , Ventricular Dysfunction, Right/therapy , Ventricular Dysfunction, Right/virology
6.
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
7.
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
8.
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
9.
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.

12.
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
13.
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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