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1.
Viruses ; 14(8):1806, 2022.
Article in English | ProQuest Central | ID: covidwho-2024292

ABSTRACT

Background and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17β-oestradiol controls HCV’s life cycle. We investigated the mechanism(s) behind oestrogen’s antiviral effect. Methods: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17β-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. Results: Stimulation of 17β-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. Conclusion: Resulting in viral control and suppression, 17β-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling.

2.
Viruses ; 14(8):1766, 2022.
Article in English | MDPI | ID: covidwho-1987991

ABSTRACT

Vaccines are the most effective means to prevent the potentially deadly effects of SARS-CoV-2 infection, but not all vaccinated individuals gain the same degree of protection. Patients undergoing chronic immunosuppressive therapy due to autoimmune diseases or liver transplants, for example, may show impaired anti-SARS-CoV-2 antibody response after vaccination. We performed a prospective observational study with parallel arms, aiming to (a) evaluate seroconversion after anti-SARS-CoV-2 mRNA vaccine administration in different subgroups of patients receiving immunosuppressive treatment for rheumatological or autoimmune diseases or to prevent organ rejection after liver transplantation and (b) identify negative predictors of IgG anti-SARS-CoV-2 development. Out of 437 eligible patients, 183 individuals were enrolled at the Rheumatology and Hepatology Tertiary Units of 'Maggiore della Carità';University Hospital in Novara: of those, 52 were healthy subjects, while among the remaining 131 patients, 30 had a diagnosis of spondyloarthritis, 25 had autoimmune hepatitis, 10 were liver transplantation recipients, 23 suffered from connective tissue diseases (including 10 cases that overlapped with other diseases), 40 were treated for rheumatoid arthritis, and 5 had vasculitis. Moreover, all patients were receiving chronic immunosuppressive therapy. The immunogenicity of mRNA COVID-19 vaccines was evaluated by measuring IgG anti-SARS-CoV-2 antibody titers before vaccination and after 10, 30, and 90 days since the first dose administration. Of the selected cohort of patients, 24.0% did not develop any detectable anti-SARS-CoV-2 IgG after a complete mRNA-based two doses primary vaccination cycle. At univariate analysis, independent predictors of an absent antibody response to vaccine were a history of liver transplantation (OR 11.5, 95% CI 2.5–53.7, p = 0.0018), the presence of a comorbid active neoplasia (OR 26.4, 95% CI 2.8–252.4, p = 0.0045), and an ongoing immunosuppressive treatment with mycophenolate (MMF) (OR 14.0, 95% CI 3.6–54.9, p = 0.0002) or with calcineurin inhibitors (OR 17.5, 95% CI 3.1–99.0, p = 0.0012). At multivariate analysis, only treatment with MMF (OR 24.8, 95% CI 5.9–103.2, p < 0.0001) and active neoplasia (OR 33.2, 95% CI 5.4–204.1, p = 0.0002) were independent predictors of seroconversion failure. These findings suggest that MMF dose reduction or suspension may be required to optimize vaccine response in these patients.

3.
Frontiers in psychiatry ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1918664

ABSTRACT

Background Mental health-related symptoms can persist over time beyond the most common respiratory clinical features of COVID-19. A recent meta-analysis underlined that mental health sequalae may be relevant for COVID-19 survivors and reported the following prevalence rates: 20% for post-traumatic stress disorder, 22% for anxiety, 36% for psychological distress, and 21% for depression. In the context of a multi-disciplinary follow-up project, we already investigated the mid-term (4 months) psychiatric outcomes in a sample of COVID-19 survivors. Patients were re-assessed after 1-year since hospital discharge. Methods Follow-up conducted after 1 year involved 196 individuals recovered from COVID-19. Patients were assessed with a multi-disciplinary approach;including both a clinical interview performed by an experienced psychiatrist, trained in the use of the Mini-International Neuropsychiatric Interview (MINI) to assess the presence of anxiety, stress, and depressive symptoms and the following self-administered questionnaires: Beck Anxiety Inventory, Beck Depression Inventory-II, Resilience Scale for Adults, Impact of Event Scale, and COVID-19 Peritraumatic Distress Index (CPDI). Results Anxiety (p < 0.0001) and depressive (p < 0.0003) symptoms registered at the clinical interview showed a significant improvement from the 4 to 12-months follow-up. Logistic regression model showed that female gender (p = 0.006), arterial hypertension (p = 0.01), obesity (0.04), anxiety (p < 0.0001), and depressive (p = 0.02) symptoms at 4-months follow-up were associated with persistence of anxiety symptoms at 12 months. At logistic regression analysis female gender (p = 0.02) and depressive symptoms at 4-months follow-up (p = 0.01) were associated with depressive symptoms after 12 months. Conclusion Severity of the disease in the acute phase, in this study, was not a determining factor in identifying subjects at risk of developing clinically relevant anxiety and depression as a consequence of COVID-19 disease. Findings from the logistic regressions suggest that the factors most affecting depression and anxiety in COVID survivors after 12 months were female gender, the presence of anxiety and depression after 4 months and some physical symptoms, not necessarily COVID-related. Impact of infection and consequent hospitalization for COVID-19 did no longer represent a relevant issue for depressive symptoms, compared to other general factors.

4.
Panminerva Med ; 2022 Jun 17.
Article in English | MEDLINE | ID: covidwho-1904100

ABSTRACT

BACKGROUND: SARS-CoV-2 is a single-stranded RNA virus, known to be the causative agent of COVID-19. As the resulting disease shows a very heterogeneous range of clinical manifestations, the identification of early biomarkers allowing patients stratification according to the expected disease severity is still an unmet clinical need. METHODS: In this observational prospective cohort study, 137 consecutive patients, testing positive for SARS-CoV-2 infection by nasopharyngeal swab RT-PCR or antigenic test, were enrolled to evaluate their plasma viral load at the time of hospitalization. RESULTS: Even if all of them had a molecular diagnosis of COVID-19, only 29 patients showed a detectable plasma SARSCoV-2 RNAemia. Such viremic patients also showed other clinical and laboratory finding alterations (increased troponin I, IL-6, RDW-CV and creatinine levels along with decreased platelet count and glomerular filtration rate). A plasma detectable RNA viral load predicted in hospital death or ICU admission with an odds ratio of 3.53 (C.I. 1.44-8.64, p=0.0058), while the lack of a detectable viral load was associated with a faster recovery, with an odds ratio of 4.06 (C.I. 1.72-9.59, p=0.0014). These findings were confirmed in multivariate models including age, sex and baseline National Early Warning Score 2 and arterial oxygen tension over inspired oxygen fraction ratio. CONCLUSIONS: Our data thus suggest that plasma viral RNA load at the time of hospital admission could represent a useful independent biomarker allowing early patients' stratification according to the expected disease evolution, and driving clinical decisions tailored on the specific needs of the individual patient.

5.
Dis Markers ; 2022: 1568352, 2022.
Article in English | MEDLINE | ID: covidwho-1832655

ABSTRACT

Reliable biomarkers allowing early patients' stratification for the risk of adverse outcomes in COVID-19 are lacking. Gas6, together with its tyrosine kinase receptors named TAM, is involved in the regulation of immune homeostasis, fibrosis, and thrombosis. Our aim was to evaluate whether Gas6, sAxl, and sMerTK could represent early predictors of disease evolution either towards a negative (death or need of ICU admission) or a positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. To this purpose, between January and May 2021 (corresponding to third pandemic wave in Italy), 139 consecutive SARS-CoV-2 positive patients were enrolled in a prospective observational study. Plasma levels of these molecules were measured by ELISA at the time of hospitalization and after 7 and 14 days. We observed that higher plasma Gas6 concentrations at hospital admission were associated with a worsening in clinical conditions while lower sMerTK concentrations at baseline and after 7 days of hospitalization were associated with a more favorable outcome. At multivariate analysis, after correction for demographic and COVID-19 severity variables (NEWS2 and PiO2/FiO2), only Gas6 measured at baseline predicted an adverse prognosis with an odds ratio of 1.03 (C.I. 1.01-10.5). At ROC curve analysis, baseline Gas6 levels higher than 58.0 ng/ml predicted a severe disease evolution with 53.3% sensitivity and 77.6% specificity (area under the curve 0.653, p = 0.01, likelihood ratio of 2.38, IQR: 1.46-3.87). Taken together, these results support the hypothesis that a dysregulation in the Gas6/TAM axis could play a relevant role in modulating the course of COVID-19 and suggest that plasma Gas6 may represent a promising prognostic laboratory parameter for this condition.


Subject(s)
COVID-19 , Intercellular Signaling Peptides and Proteins , Blood Proteins , Humans , Intercellular Signaling Peptides and Proteins/blood , Proto-Oncogene Proteins , Receptor Protein-Tyrosine Kinases/metabolism , SARS-CoV-2
6.
Dis Markers ; 2022: 3528312, 2022.
Article in English | MEDLINE | ID: covidwho-1723960

ABSTRACT

BACKGROUND: SARS-CoV-2 is responsible for COVID-19, a clinically heterogeneous disease, ranging from being completely asymptomatic to life-threating manifestations. An unmet clinical need is the identification at disease onset or during its course of reliable biomarkers allowing patients' stratification according to disease severity. In this observational prospective cohort study, patients' immunologic and laboratory signatures were analyzed to identify independent predictors of unfavorable (either death or intensive care unit admission need) or favorable (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. METHODS: Between January and May 2021 (third wave of the pandemic), we enrolled 139 consecutive SARS-CoV-2 positive patients hospitalized in Northern Italy to study their immunological and laboratory signatures. Multiplex cytokine, chemokine, and growth factor analysis, along with routine laboratory tests, were performed at baseline and after 7 days of hospital stay. RESULTS: According to their baseline characteristics, the majority of our patients experienced a moderate to severe illness. At multivariate analysis, the only independent predictors of disease evolution were the serum concentrations of IP-10 (at baseline) and of C-reactive protein (CRP) after 7 days of hospitalization. Receiver-operating characteristic (ROC) curve analysis confirmed that baseline IP - 10 > 4271 pg/mL and CRP > 2.3 mg/dL at 7 days predict a worsening in clinical conditions (87% sensitivity, 66% specificity, area under the curve (AUC) 0.772, p < 0.001 and 83% sensitivity, 73% specificity, AUC 0.826, p < 0.001, respectively). CONCLUSIONS: According to our results, baseline IP-10 and CRP after 7 days of hospitalization could be useful in driving clinical decisions tailored to the expected disease trajectory in hospitalized COVID-19 patients.


Subject(s)
Biomarkers/blood , COVID-19/immunology , Chemokine CXCL10/blood , Nerve Tissue Proteins/blood , Aged , Area Under Curve , C-Reactive Protein , COVID-19/blood , COVID-19/mortality , Female , Hospitalization , Humans , Italy , Male , Middle Aged , Patient Acuity , Prognosis , Prospective Studies
7.
J Clin Med ; 11(3)2022 Jan 29.
Article in English | MEDLINE | ID: covidwho-1667215

ABSTRACT

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01-1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05-6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19-10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13-8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered.

8.
Panminerva Med ; 63(4): 478-481, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1591662

ABSTRACT

BACKGROUND: The Coronavirus disease (COVID-19) outbreak is putting the European National Health Systems under pressure. Interestingly, Emergency Department (ED) referrals for other reasons than COVID-19 seem to have declined steeply. In the present paper, we aimed to verify how the COVID-19 outbreak changed ED referral pattern. METHODS: We retrospectively reviewed the clinical records of patients referred to the ED of a University Hospital in Northern Italy from 1 March to 13 April 2020. We compared the following data with those belonging to the same period in 2019: number of EDs accesses, rate of hospital admission, frequencies of the most common causes of ED referral, priority codes of access. RESULTS: The number of ED referrals during the COVID-19 outbreak was markedly reduced when compared to the same period in 2019 (3059 vs. 5691; -46.3%). Conversely, the rate of hospital admission raised from 16.9% to 35.4% (P<0.0001), with a shift toward higher priority codes of ED admission. In 2020, we observed both a reduction of the number of patients referred for both traumatic (513, 16.8% vs. 1544, 27.1%; χ2=118.7, P<0.0001) and non-traumatic (4147 vs. 2546) conditions. Among the latter, suspected COVID-19 accounted for 1101 (43.2%) accesses. CONCLUSIONS: The COVID-19 pandemic completely changed the pattern of ED referral in Italy, with a marked reduction of the accesses to the hospitals. This could be related to a limited exposure to traumas and to a common fear of being infected during EDs in-stay. This may limit the misuse of EDs for non-urgent conditions but may also delay proper referrals for urgent conditions.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Emergency Service, Hospital/statistics & numerical data , Referral and Consultation/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Emergency Service, Hospital/trends , Female , Health Services Accessibility , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Referral and Consultation/trends , Retrospective Studies , SARS-CoV-2
9.
Minerva Med ; 113(1): 158-171, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1552034

ABSTRACT

INTRODUCTION: Coronavirus disease 19 (COVID-19) is an infectious disease caused by the newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have plenty of data about the clinical features of the disease's acute phase, while little is known about the long-term consequences on survivors. EVIDENCE ACQUISITION: We aimed to review systematically emerging evidence about clinical and functional consequences of COVID-19 pneumonia months after hospital discharge. EVIDENCE SYNTHESIS: Current evidence supports the idea that a high proportion of COVID-19 survivors complain of symptoms months after the acute illness phase, being fatigue and reduced tolerance to physical effort the most frequently reported symptom. The strongest association for these symptoms is with the female gender, while disease severity seems less relevant. Respiratory symptoms are associated with a decline in respiratory function and, conversely, seem to be more frequent in those who experienced a more severe acute pneumonia. Current evidence highlighted a persistent motor impairment which is, again, more prevalent among those survivors who experienced a more severe acute phase of the disease. Additionally, the persistence of symptoms is a primary determinant of mental health outcome, with anxiety, depression, sleep disturbances, and post-traumatic stress symptoms being commonly reported in COVID-19 survivors. CONCLUSIONS: Current literature highlights the importance of a multidisciplinary approach to Coronavirus Disease 19 since the sequelae appear to involve different organs and systems. Given the pandemic outbreak's size, this is a critical public health issue: a better insight on this topic should inform clinical decisions about the modalities of follow-up for COVID-19 survivors.


Subject(s)
COVID-19 , Anxiety/etiology , COVID-19/complications , Fatigue/etiology , Female , Humans , Pandemics , SARS-CoV-2
11.
Sci Rep ; 11(1): 22666, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1528025

ABSTRACT

Many coronavirus disease 2019 (Covid-19) survivors show symptoms months after acute illness. The aim of this work is to describe the clinical evolution of Covid-19, one year after discharge. We performed a prospective cohort study on 238 patients previously hospitalized for Covid-19 pneumonia in 2020 who already underwent clinical follow-up 4 months post-Covid-19. 200 consented to participate to a 12-months clinical assessment, including: pulmonary function tests with diffusing lung capacity for carbon monoxide (DLCO); post-traumatic stress (PTS) symptoms evaluation by the Impact of Event Scale (IES); motor function evaluation (by Short Physical Performance Battery and 2 min walking test); chest Computed Tomography (CT). After 366 [363-369] days, 79 patients (39.5%) reported at least one symptom. A DLCO < 80% was observed in 96 patients (49.0%). Severe DLCO impairment (< 60%) was reported in 20 patients (10.2%), related to extent of CT scan abnormalities. Some degree of motor impairment was observed in 25.8% of subjects. 37/200 patients (18.5%) showed moderate-to-severe PTS symptoms. In the time elapsed from 4 to 12 months after hospital discharge, motor function improves, while respiratory function does not, being accompanied by evidence of lung structural damage. Symptoms remain highly prevalent one year after acute illness.


Subject(s)
COVID-19/complications , Hospitalization , Aged , COVID-19/diagnosis , COVID-19/diagnostic imaging , COVID-19/epidemiology , Carbon Monoxide/metabolism , Female , Humans , Italy/epidemiology , Logistic Models , Male , Mental Health , Middle Aged , Motor Activity , Patient Acuity , Patient Discharge , Prevalence , Prospective Studies , Pulmonary Diffusing Capacity , Respiratory Function Tests , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/etiology , Survivors , Tomography, X-Ray Computed , Walk Test
12.
Sci Rep ; 11(1): 13796, 2021 07 05.
Article in English | MEDLINE | ID: covidwho-1297316

ABSTRACT

The COVID-19 pandemic is still raging in most countries. Although the recent mass vaccination campaign has opened a new chapter in the battle against SARS-CoV-2, the world is still far from herd immunity. There is an urgent need to identify healthy people at high risk of contracting COVID-19, as well as supplements and nutraceuticals that can reduce the risk of infection or mitigate symptoms. In the present study, a metabolic phenotype that could protect individuals from SARS-CoV-2 infection or predispose them to developing COVID-19 was investigated. Untargeted metabolomics was performed on serum samples collected from 51 healthcare workers who were in good health at the beginning of the COVID-19 outbreak in Italy, and who were later exposed to the same risk of developing COVID-19. Half of them developed COVID-19 within three weeks of the blood collection. Our results demonstrate the presence of a specific signature associated with protection from SARS-CoV-2. Circulating monolaurin, which has well-known antiviral and antibacterial properties, was higher in protected subjects, suggesting a potential defensive role against SARS-CoV-2 infection; thus, dietary supplements could boost the immune system against this infection. In addition, our data demonstrate that people with higher levels of cholesterol are at higher risk of developing COVID-19. The present study demonstrates that metabolomics can be of great help for developing personalized medicine and for supporting public healthcare strategies. Studies with larger cohorts of subjects are necessary to confirm our findings.


Subject(s)
COVID-19/prevention & control , Disease Outbreaks/prevention & control , Metabolomics , SARS-CoV-2/pathogenicity , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Health Personnel/statistics & numerical data , Humans , Immunity, Herd/physiology , Italy
13.
Front Psychiatry ; 12: 667385, 2021.
Article in English | MEDLINE | ID: covidwho-1285349

ABSTRACT

Background: Although the usual primary clinical manifestation of Coronavirus disease (COVID-19) is respiratory, several non-respiratory symptoms have been described, including neuropsychiatric ones. The aim of this study was to investigate the mid-term mental health outcomes in patients recovered from COVID-19, 3-4 months after discharge from the University Hospital Maggiore della Carità, Novara, Italy. Furthermore, we investigated the possible association of the mid-term mental health consequences of the COVID-19 infection with patients' clinical current status, persistent physical impairment and severity of acute phase of the disease. Methods: Prospective study involving 238 individuals recovered from COVID-19. In the context of a multi-disciplinary approach, patients' assessment included both a clinical interview performed by an experienced psychiatrist, trained in the use of the Mini-International Neuropsychiatric Interview to assess the presence of anxiety and depressive symptoms and self-administered questionnaires: Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Resilience Scale for Adults (RSA), Impact of Event Scale (IES). Results: At the psychiatric assessment 32.9 and 29.5% of participants showed anxiety and depressive symptoms, respectively. Changes in appetite and sleep patterns emerged for 15.6 and 31.2% of patients. According to the self-administered questionnaires, 7.1% of participants had moderate-severe anxiety levels (BAI), while 10.5% had mild to severe depression (BDI-II). Twenty-six (11%) participants were referred to further psychiatric consultation. Psychiatric symptoms showed no correlation with acute COVID-19 severity; in our sample patients with depressive symptoms at the clinical interview, as well as those with mild to severe levels of depression according to BDI-II scores, had lower forced expiratory volume in the 1st second (FEV1) values than those without and greater odds for persistent, poor tolerance for physical efforts. Conclusions: As could be expected, an approach including both a psychiatric interview and the use of self-administered questionnaires is likely to capture the psychiatric outcome of patients recovered from COVID-19 better than questionnaires alone. Anxiety and depressive symptoms at follow-up had no correlation with the severity of COVID acute manifestations, but rather with ongoing and persistent physical symptoms. Further studies and longer follow-up duration will allow a better understanding of the complex relationship between residual physical symptoms, quality of life and psychological health.

14.
J Thromb Thrombolysis ; 52(3): 746-753, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1263169

ABSTRACT

Patients with Coronavirus Disease-2019 (COVID-19) have haemostatic dysfunction and are at higher risk of thrombotic complications. Although age is a major risk factor for outcome impairment in COVID-19, its impact on coagulative patterns here is still unclear. We investigated the association of Endogenous Thrombin Potential (ETP) with thrombotic and haemorrhagic events according to different ages in patients admitted for COVID-19. A total of 27 patients with COVID-19-related pneumonia, without need for intensive care unit admission or mechanical ventilation at hospital presentation, and 24 controls with non-COVID-19 pneumonia were prospectively included. ETP levels were measured on admission. Patients were evaluated for major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke, transient ischemic attack, venous thromboembolism) and bleeding complications [according to Bleeding Academic Research Consortium (BARC) definition] during in-hospital stay. COVID-19 patients had similar ETP levels compared to controls (AUC 93 ± 24% vs 99 ± 21%, p = 0.339). In the COVID-19 cohort, patients with in-hospital MACE showed lower ETP levels on admission vs those without (AUC 86 ± 14% vs 95 ± 27%, p = 0.041), whereas ETP values were comparable in patients with or without bleeding (AUC 82 ± 16% vs 95 ± 26%, p = 0.337). An interaction between age and ETP levels for both MACE and bleeding complications was observed, where a younger age was associated with an inverse relationship between ETP values and adverse event risk (pint 0.018 for MACE and 0.050 for bleeding). Patients with COVID-19 have similar thrombin potential on admission compared to those with non-COVID-19 pneumonia. In younger COVID-19 patients, lower ETP levels were associated with a higher risk of both MACE and bleeding.


Subject(s)
COVID-19/complications , Hemostasis , Hospitalization , Thrombin/metabolism , Thrombosis/etiology , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , Case-Control Studies , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Assessment , Risk Factors , Thrombosis/blood , Thrombosis/mortality , Thrombosis/therapy , Time Factors
15.
Dis Markers ; 2021: 8863053, 2021.
Article in English | MEDLINE | ID: covidwho-1231192

ABSTRACT

INTRODUCTION: The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. MATERIALS AND METHODS: In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients (F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. RESULTS: At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) (χ 2 10.4; p < 0.001), neutrophil-to-lymphocyte (NL) ratio (χ 2 7.6; p = 0.006), and platelet count (χ 2 5.39; p = 0.02), along with age (χ 2 87.6; p < 0.001) and gender (χ 2 17.3; p < 0.001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality (OR) = 3.40 (2.40-4.82), while the OR for a RDW > 13.7% was 4.09 (2.87-5.83); a platelet count > 166,000/µL was, conversely, protective (OR: 0.45 (0.32-0.63)). CONCLUSION: Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.


Subject(s)
Blood Cell Count , COVID-19/blood , COVID-19/mortality , Clinical Decision Rules , Hospital Mortality , Severity of Illness Index , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , Female , Humans , Italy/epidemiology , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies
16.
Eur J Phys Rehabil Med ; 57(2): 199-207, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1224409

ABSTRACT

BACKGROUND: COVID-19 has been mainly investigated concerning the acute and subacute phase implications and management. Meanwhile, few studies focused on the midterm sequelae, which still remain largely unknown. AIM: To assess the physical performance of COVID-19 survivors at 3 to 6 months from Hospital discharge. DESIGN: A cross-sectional study focused on mid-term functional outcomes evaluation in COVID-19 survivors. SETTING: Outpatients who had been previously hospitalized due to COVID-19 from March to May 2020 at the University Hospital of Novara, Italy. POPULATION: We enrolled 204 patients, of which 60% were men, with the mean age of 57.9 years. METHODS: Patients firstly underwent the short physical performance battery test (SPPB), which is composed of a series of physical tests assessing the lower limb function and the functional status of the subjects. Subsequently, based on SPPB results, patients' cardiorespiratory fitness performance was further investigated. Patients with normal SPPB score (SPPB>10) underwent the 2-minute walking test (2MWT) whereas, in order to safely test the cardiorespiratory function, in patients with abnormal SPPB score (SPPB≤10) the 1-minute sit-to-stand test (1MSTST) was performed. It should be noted that the 1MSTST can be safely performed even by subjects with compromised walking ability. RESULTS: Overall, 66 patients (32% of our sample) showed an impaired physical performance at 3 to 6 months after hospital discharge. In particular, 29 patients presented an SPPB score ≤10, and the 1MSTST confirmed this status in the whole group (100%) compared to the reference values for age and sex. Besides, among patients with a normal SPPB score, 37 showed a lower sex- and age-matched 2MWT score. Finally, a significant association between Intensive Care Unit hospitalization or mechanical ventilation and physical impairment was observed together with a significant association between the walking ability (measured with SPPB and 2MWT) and the number of comorbidities. CONCLUSIONS: A residual physical and functional impairment was observed in COVID-19 survivors at mid-term evaluation after hospitalization. CLINICAL REHABILITATION IMPACT: Considering the current COVID-19 epidemiology, we might expect a tremendous burden of disability in the next future. Thus, an appropriate clinical rehabilitation pathway must be implemented.


Subject(s)
COVID-19/rehabilitation , Disability Evaluation , Disabled Persons/statistics & numerical data , Physical Functional Performance , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/physiopathology , Cross-Sectional Studies , Female , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , SARS-CoV-2 , Walk Test , Young Adult
17.
Intern Emerg Med ; 16(4): 1005-1015, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1202836

ABSTRACT

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio < 100. The latter, significantly benefited by the early use of non-invasive mechanical ventilation. Our study identified PaO2/FiO2 ratio at admission and comorbidity as the main alert signs to inform clinical decisions and resource allocation in non-critically ill COVID-19 patients admitted to IMU.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Hospitalization , Internal Medicine , Adult , Aged , Aged, 80 and over , COVID-19/complications , Cohort Studies , Critical Care , Hospital Mortality , Humans , Italy , Middle Aged , Respiration, Artificial , Survival Rate
18.
J Thromb Thrombolysis ; 52(3): 782-790, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1111318

ABSTRACT

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/therapy , Enoxaparin/administration & dosage , Hospitalization , Thromboembolism/prevention & control , Aged , Aged, 80 and over , Anticoagulants/adverse effects , COVID-19/blood , COVID-19/diagnosis , COVID-19/mortality , Enoxaparin/adverse effects , Female , Hospital Mortality , Humans , Italy , Male , Middle Aged , Protective Factors , Respiration, Artificial , Retrospective Studies , Risk Assessment , Risk Factors , Thromboembolism/blood , Thromboembolism/diagnosis , Thromboembolism/mortality , Time Factors , Treatment Outcome
20.
Eur J Phys Rehabil Med ; 57(2): 199-207, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1077000

ABSTRACT

BACKGROUND: COVID-19 has been mainly investigated concerning the acute and subacute phase implications and management. Meanwhile, few studies focused on the midterm sequelae, which still remain largely unknown. AIM: To assess the physical performance of COVID-19 survivors at 3 to 6 months from Hospital discharge. DESIGN: A cross-sectional study focused on mid-term functional outcomes evaluation in COVID-19 survivors. SETTING: Outpatients who had been previously hospitalized due to COVID-19 from March to May 2020 at the University Hospital of Novara, Italy. POPULATION: We enrolled 204 patients, of which 60% were men, with the mean age of 57.9 years. METHODS: Patients firstly underwent the short physical performance battery test (SPPB), which is composed of a series of physical tests assessing the lower limb function and the functional status of the subjects. Subsequently, based on SPPB results, patients' cardiorespiratory fitness performance was further investigated. Patients with normal SPPB score (SPPB>10) underwent the 2-minute walking test (2MWT) whereas, in order to safely test the cardiorespiratory function, in patients with abnormal SPPB score (SPPB≤10) the 1-minute sit-to-stand test (1MSTST) was performed. It should be noted that the 1MSTST can be safely performed even by subjects with compromised walking ability. RESULTS: Overall, 66 patients (32% of our sample) showed an impaired physical performance at 3 to 6 months after hospital discharge. In particular, 29 patients presented an SPPB score ≤10, and the 1MSTST confirmed this status in the whole group (100%) compared to the reference values for age and sex. Besides, among patients with a normal SPPB score, 37 showed a lower sex- and age-matched 2MWT score. Finally, a significant association between Intensive Care Unit hospitalization or mechanical ventilation and physical impairment was observed together with a significant association between the walking ability (measured with SPPB and 2MWT) and the number of comorbidities. CONCLUSIONS: A residual physical and functional impairment was observed in COVID-19 survivors at mid-term evaluation after hospitalization. CLINICAL REHABILITATION IMPACT: Considering the current COVID-19 epidemiology, we might expect a tremendous burden of disability in the next future. Thus, an appropriate clinical rehabilitation pathway must be implemented.


Subject(s)
COVID-19/rehabilitation , Disability Evaluation , Disabled Persons/statistics & numerical data , Physical Functional Performance , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/physiopathology , Cross-Sectional Studies , Female , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , SARS-CoV-2 , Walk Test , Young Adult
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