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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316935

ABSTRACT

Introduction: High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. Methods: : In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. Results: hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO 2 . Changes of hsTnT, D-dimer and CRP were related but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. Conclusions: : D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.

2.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327541

ABSTRACT

Several compounds have been tested against SARS-CoV-2;at present, COVID-19 treatments decrease the deleterious inflammatory response and acute lung injury. However, the best therapeutic response would be expected by combining anti-inflammatory properties, while concomitantly blocking viral replication. These combined effects should drastically reduce both infection rate and severe complications induced by novel SARS-CoV-2 variants. Therefore, we explored the antiviral potency of a class of anti-inflammatory compounds that inhibit the N-Acylethanolamine acid amidase (NAAA). This enzyme catalyzes the hydrolysis of palmitoylethanolamide (PEA), a bioactive lipid that mediates anti-inflammatory and analgesic activity through the activation of peroxisome proliferator receptor-α (PPAR-α). Similarly, this pathway is likely to be a significant target to impede viral replication since PPAR-α activation leads to dismantling of lipid droplets, where viral replication of Flaviviruses and Coronaviruses occurs. Here, we show that either genetic or pharmacological inhibition of the NAAA enzyme leads to five-fold reduction in the replication of both SARS-CoV-2 and ZIKV in various cell lines. Once NAAA enzyme is blocked, both ZIKV and SARS CoV-2 replication decrease, which parallels a sudden five-fold decrease in virion release. These effects induced by NAAA inhibition occurs concomitantly with stimulation of autophagy during infection. Remarkably, parallel antiviral and anti-inflammatory effects of NAAA antagonism were confirmed in ex-vivo experiments, within SARS-CoV-2 infected human PBMC cells, in which both viral genomes and TNF-α production drop by ~60%. It is known that macrophages contribute to viral spread, excessive inflammation and macrophage activation syndrome that NAAA inhibitors might prevent, reducing the macrophage-induced acute respiratory distress syndrome and subsequent death of COVID-19 patients.

3.
Sci Rep ; 11(1): 20239, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1467128

ABSTRACT

Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P < 0.001). Using a machine learning approach, ePWV provided incremental prognostic value and improved reclassification for mortality over the core model including age, sex and comorbidities [AUC (core model + ePWV vs. core model) = 0.864 vs. 0.755]. ePWV provided similar prognostic value when pulse pressure or hs-Troponin were added to the core model or over its components including age and mean blood pressure (p < 0.05 for all). The optimal prognostic ePWV value was 13.0 m/s. ePWV conferred additive discrimination (AUC: 0.817 versus 0.779, P < 0.001) and reclassification value (NRI = 0.381, P < 0.001) over the 4C Mortality score, a validated score for predicting mortality in COVID-19 and the Charlson comorbidity index. We suggest that calculation of ePWV, a readily applicable estimation of arterial stiffness, may serve as an additional clinical tool to refine risk stratification of hospitalized patients with COVID-19 beyond established risk factors and scores.


Subject(s)
COVID-19/mortality , Cardiovascular Diseases/epidemiology , Vascular Stiffness , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Italy/epidemiology , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Risk Factors , United Kingdom/epidemiology
4.
Acta Paediatr ; 110(10): 2796-2801, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1294944

ABSTRACT

AIM: To ascertain a delay in attendances to the emergency department (ED) during 2020 lockdown. METHODS: Area-based cohort study on paediatric (0-15 years) attendances resulting in hospital admission in Tuscany, Italy, in February-May 2020, and the corresponding periods in 2018-19. We analysed times from symptom onset to arrival, the odds of arriving late (>90th centile of time) and paediatricians' judgements of a late presentation by logistic models. RESULTS: As expected, ED attendance fell sharply (-62%) in 2020 vs 2018-19. As for cases studied (455 in 2020 and 1161 in 2018-19), we documented a delay in arrival to the ED in 2020 versus 2018-19 for several groups of diagnoses, namely gastroenteritis, sepsis, wounds, burns and infections overall. Time to presentation over 90th centile was also higher in 2020 (odds ratio, OR: 1.44; 95% confidence interval: 1.00, 2.06), as were paediatricians' judgements of a late arrival (18.9% of cases in 2020 vs. 13.4% in 2018-19; OR: 1.58; 1.14, 2.19) CONCLUSION: In a population-based cohort, delayed attendances to ED ascertained both subjectively and objectively convey the message to families and to paediatricians to seek hospital care in case of severe or unremitting symptoms and not to wait longer than they normally would.


Subject(s)
COVID-19 , Pandemics , Child , Cohort Studies , Communicable Disease Control , Emergency Service, Hospital , Humans , Italy/epidemiology , Retrospective Studies , SARS-CoV-2
5.
Sci Rep ; 11(1): 6515, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1147151

ABSTRACT

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.


Subject(s)
Blood Coagulation Disorders/diagnosis , COVID-19/pathology , Heart Diseases/diagnosis , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Female , Fibrin Fibrinogen Degradation Products/analysis , Heart Diseases/etiology , Hemodynamics , Heparin, Low-Molecular-Weight/therapeutic use , Hospital Mortality , Humans , Inflammation , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Prospective Studies , Risk , SARS-CoV-2/isolation & purification , Troponin T/blood
6.
Pediatrics ; 146(6)2020 12.
Article in English | MEDLINE | ID: covidwho-793123

ABSTRACT

BACKGROUND: Variability in presentation of children with coronavirus disease 2019 (COVID-19) is a challenge in emergency departments (EDs) in terms of early recognition, which has an effect on disease control and prevention. We describe a cohort of 170 children with COVID-19 and differences with the published cohorts. METHODS: Retrospective chart reviews on children (0-18 years) evaluated in 17 Italian pediatric EDs. RESULTS: In our cohort (median age of 45 months; interquartile range of 4 months-10.7 years), we found a high number of patients <1 year with COVID-19 disease. The exposure happened mainly (59%) outside family clusters; 22% had comorbidities. Children were more frequently asymptomatic (17%) or with mild diseases (63%). Common symptoms were cough (43%) and difficulty feeding (35%). Chest computed tomography, chest radiograph, and point-of-care lung ultrasound were used in 2%, 36%, and 8% of cases, respectively. Forty-three percent of patients were admitted because of their clinical conditions. The minimal use of computed tomography and chest radiograph may have led to a reduced identification of moderate cases, which may have been clinically classified as mild cases. CONCLUSIONS: Italian children evaluated in the ED infrequently have notable disease symptoms. For pediatrics, COVID-19 may have rare but serious and life-threatening presentations but, in the majority of cases, represents an organizational burden for the ED. These data should not lower the attention to and preparedness for COVID-19 disease because children may represent a source of viral transmission. A clinically driven classification, instead of a radiologic, could be more valuable in predicting patient needs and better allocating resources.


Subject(s)
COVID-19/epidemiology , Emergency Service, Hospital/statistics & numerical data , SARS-CoV-2 , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/diagnostic imaging , COVID-19 Testing/statistics & numerical data , Child , Child, Preschool , Female , Humans , Infant , Italy/epidemiology , Male , Point-of-Care Testing/statistics & numerical data , Radiography, Thoracic/statistics & numerical data , Retrospective Studies , Symptom Assessment , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Tomography, X-Ray Computed/statistics & numerical data , Ultrasonography/statistics & numerical data
7.
Obes Res Clin Pract ; 14(3): 205-209, 2020.
Article in English | MEDLINE | ID: covidwho-526634

ABSTRACT

INTRODUCTION: On the last three months the new SARS-COV-2 coronavirus has created a pandemic, rapidly spreading all around the world. The aim of the study is to investigate whether obesity impacts on COVID-19 morbidity. METHODS: One hundred consecutive patients with COVID-19 pneumonia admitted in our Medical Unit were evaluated. Anthropometric parameters and past medical history were registered. Nasopharyngeal swab samples and biochemical analysis were obtained at admission and during hospital stay. RESULTS: Patients with (OB, 29) and without obesity (N-OB, 71) were similar in age, gender and comorbidities, with the exception of hypertension that was more frequent in OB group. At admission, inflammatory markers were higher in OB than N-OB group. OB group showed a worse pulmonary clinical picture, with lower PaO2 (57 ± 15 vs. 68 ± 14 mmHg, p = 0.042), and SaO2 (88 ± 6 vs. 92 ± 5%, p = 0.049) at admission consequently requiring higher volumes of oxygen (Fi02: 38 ± 15 vs. 29 ± 19%, p = 0.047) and a longer period to achieve oxygen weaning (10 ± 6 vs. 15 ± 7 days, p = 0.03). OB group also had positive swabs for longer time (19 ± 8 vs. 13 ± 7, days, p = 0.002), and required longer hospital stay (21 ± 8 vs. 13 ± 8, days, p = 0.0008). Partial least square regression analysis showed that BMI, age and CRP at admission were related to longer length of hospital stay, and time for negative swab. On the contrary, in this cohort, obesity did not predict higher mortality. CONCLUSIONS: Subjects with obesity affected by COVID-19 require longer hospitalization, more intensive and longer oxygen treatment, and they may have longer SARS-COV-2 shedding.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Length of Stay/statistics & numerical data , Obesity/complications , Obesity/physiopathology , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Virus Shedding/physiology , Aged , COVID-19 , Cohort Studies , Female , Humans , Italy , Male , Pandemics , Retrospective Studies , SARS-CoV-2
8.
Eur J Pediatr ; 179(8): 1315-1323, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-505959

ABSTRACT

Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: • There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: • Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. • However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Adolescent , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Child , Child, Preschool , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/statistics & numerical data , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/etiology , Female , Humans , Infant , Infant, Newborn , Italy/epidemiology , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Respiratory Therapy/methods , Respiratory Therapy/statistics & numerical data , Retrospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
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