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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311148

ABSTRACT

Early recognition of risk and start of treatment may improve unfavorable outcome of COVID-19. In the SAVE-MORE double-blind randomized trial, 594 patients with pneumonia without respiratory dysfunction at risk as defined by plasma suPAR (soluble urokinase plasminogen activator receptor) ≥ 6 ng/ml were 1:2 randomized to subcutaneous placebo or 100 mg anakinra once daily for 10 days;85.9% were co-administered dexamethasone. After 28 days, anakinra-treated patients were distributed to lower strata of the 11-point World Health Organization ordinal Clinical Progression Scale (WHO-CPS) (adjusted odds ratio-OR 0.36;95%CI 0.26–0.50;P < 0.001);anakinra protected from severe disease or death (≥ 6 points of WHO-CPS) (OR: 0.46;P: 0.010). The median WHO-CPS decrease in the placebo and anakinra groups was 3 and 4 points (OR 0.40;P < 0.0001);the median decrease of SOFA score was 0 and 1 points (OR 0.63;P: 0.004). 28-day mortality decreased (hazard ratio: 0.45;P: 0.045) and hospital stay was shorter. (Sponsored by the Hellenic Institute for the Study of Sepsis ClinicalTrials.gov identifier, NCT04680949)

2.
Information ; 13(2):76, 2022.
Article in English | MDPI | ID: covidwho-1674676

ABSTRACT

The health emergency linked to the SARS-CoV-2 pandemic has highlighted problems in the health management of chronic patients due to their risk of infection, suggesting the need of new methods to monitor patients. People living with HIV/AIDS (PLWHA) represent a paradigm of chronic patients where an e-health-based remote monitoring could have a significant impact in maintaining an adequate standard of care. The key objective of the study is to provide both an efficient operating model to “follow”the patient, capture the evolution of their disease, and establish proximity and relief through a remote collaborative model. These dimensions are collected through a dedicated mobile application that triggers questionnaires on the basis of decision-making algorithms, tagging patients and sending alerts to staff in order to tailor interventions. All outcomes and alerts are monitored and processed through an innovative e-Clinical platform. The processing of the collected data aims into learning and evaluating predictive models for the possible upcoming alerts on the basis of past data, using machine learning algorithms. The models will be clinically validated as the study collects more data, and, if successful, the resulting multidimensional vector of past attributes will act as a digital composite biomarker capable of predicting HIV-related alerts. Design: All PLWH > 18 sears old and stable disease followed at the outpatient services of a university hospital (n = 1500) will be enrolled in the interventional study. The study is ongoing, and patients are currently being recruited. Preliminary results are yielding monthly data to facilitate learning of predictive models for the alerts of interest. Such models are learnt for one or two months of history of the questionnaire data. In this manuscript, the protocol—including the rationale, detailed technical aspects underlying the study, and some preliminary results—are described. Conclusions: The management of HIV-infected patients in the pandemic era represents a challenge for future patient management beyond the pandemic period. The application of artificial intelligence and machine learning systems as described in this study could enable remote patient management that takes into account the real needs of the patient and the monitoring of the most relevant aspects of PLWH management today.

3.
BMC Infect Dis ; 21(1): 1170, 2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1526605

ABSTRACT

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , Immunization, Passive , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
5.
Nat Med ; 27(10): 1752-1760, 2021 10.
Article in English | MEDLINE | ID: covidwho-1392877

ABSTRACT

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/ß inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml-1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.


Subject(s)
COVID-19/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Receptors, Urokinase Plasminogen Activator/blood , Aged , COVID-19/virology , Double-Blind Method , Female , Humans , Interleukin 1 Receptor Antagonist Protein/adverse effects , Male , Middle Aged , Placebos , SARS-CoV-2/isolation & purification
6.
EClinicalMedicine ; 27: 100553, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1385448

ABSTRACT

BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

7.
JCI Insight ; 6(13)2021 06 18.
Article in English | MEDLINE | ID: covidwho-1346128

ABSTRACT

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.


Subject(s)
Arthritis, Rheumatoid/immunology , COVID-19/immunology , Monocytes/immunology , Neutrophils/immunology , Osteopontin/immunology , Arthritis, Rheumatoid/metabolism , B7-H1 Antigen/immunology , Bronchoalveolar Lavage Fluid/immunology , CD48 Antigen/immunology , COVID-19/chemically induced , COVID-19/metabolism , Fatty Acid-Binding Proteins/immunology , Humans , Lectins/immunology , Lipopolysaccharide Receptors/immunology , Lipopolysaccharide Receptors/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Lung/pathology , Macrophages/immunology , Macrophages/metabolism , Membrane Glycoproteins/immunology , Monocytes/metabolism , Neutrophils/metabolism , Osteopontin/blood , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Immunologic/immunology , S100A12 Protein/immunology , S100A12 Protein/metabolism , Synovial Membrane/immunology , Tomography, X-Ray Computed
8.
Viruses ; 13(7)2021 07 19.
Article in English | MEDLINE | ID: covidwho-1344395

ABSTRACT

OBJECTIVES: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. METHODS: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. RESULTS: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). CONCLUSIONS: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.


Subject(s)
Disease Eradication/statistics & numerical data , HIV Infections/virology , Hepacivirus/genetics , Hepatitis C/prevention & control , Lipid Metabolism , Antiviral Agents/therapeutic use , Cholesterol/blood , Cholesterol, LDL/blood , Cohort Studies , Female , Genotype , Hepacivirus/classification , Hepacivirus/drug effects , Hepatitis C/drug therapy , Humans , Italy , Male , Middle Aged , Sustained Virologic Response
9.
J Healthc Eng ; 2021: 5556207, 2021.
Article in English | MEDLINE | ID: covidwho-1314165

ABSTRACT

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.


Subject(s)
Antimalarials/adverse effects , Antimalarials/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Hospital Mortality , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Aged , Aged, 80 and over , COVID-19/physiopathology , Cluster Analysis , Female , Humans , Italy , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/drug effects , Severity of Illness Index , Treatment Outcome
10.
Front Med (Lausanne) ; 8: 639970, 2021.
Article in English | MEDLINE | ID: covidwho-1285307

ABSTRACT

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

11.
Intern Emerg Med ; 17(1): 53-64, 2022 01.
Article in English | MEDLINE | ID: covidwho-1220529

ABSTRACT

INTRODUCTION: Antibody response plays a fundamental role in the natural history of infectious disease. A better understanding of the immune response in patients with SARS-CoV-2 infection could be important for identifying patients at greater risk of developing a more severe form of disease and with a worse prognosis. METHODS: We performed a cross-sectional analysis to determine the presence and the levels of both anti-SARS-CoV-2 IgG and IgA in a cohort of hospitalized patients with confirmed infection at different times in the natural history of the disease. Patients enrolled when admitted at the emergency department were prospectively followed up during hospital stay. RESULTS: Overall, 131 patients were considered with a total of 237 samples processed. Cross-sectional analysis showed that seroconversion for IgA seems to occur between days 6 and 15, while IgG response seems to occur slightly later, peaking at day 20 after symptoms onset. Both IgA and IgG were maintained beyond 2 months. Severe patients showed a higher IgA response compared with mild patients when analyzing optical density (8.3 versus 5.6, p < 0.001). Prospective analysis conducted on 55 patients confirmed that IgA appear slightly earlier than IgG. After stratifying for the severity of disease, both the IgA and IgG responses were more vigorous in severe cases. Moreover, while IgG tended to stabilize, there was a relevant decline after the first month of IgA levels in mild cases. CONCLUSION: IgA and IgG antibody response is closely related, although seroconversion for IgA occurs earlier. Both IgA and IgG are maintained beyond 2 months. Severe patients showed a more vigorous IgA and IgG response. IgA levels seem to decline after 1 month since the onset of symptoms in mild cases. Our results should be interpreted with cautions due to several limitations in our study, mainly the small number of cases, lack of data on viral load and clinical setting.


Subject(s)
COVID-19 , Antibody Formation , Cross-Sectional Studies , Hospitals , Humans , Immunoglobulin A , Immunoglobulin G , Referral and Consultation , SARS-CoV-2
12.
Thromb Haemost ; 121(8): 1054-1065, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1112023

ABSTRACT

INTRODUCTION: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. METHODS: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. CONCLUSION: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Heparin, Low-Molecular-Weight/therapeutic use , Heparin/therapeutic use , Thrombophilia/etiology , Thrombophilia/prevention & control , Aged , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/drug therapy , Female , Hospital Mortality , Humans , Italy/epidemiology , Male , Middle Aged , Retrospective Studies , Survival Analysis , Thrombophilia/blood
13.
Trials ; 21(1): 875, 2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-886002

ABSTRACT

OBJECTIVES: The primary objective is to demonstrate that COVID-19 convalescent plasma (CCP) prevents progression to severe pneumonia in elderly COVID-19 pneumonia patients with chronic comorbidities. Secondary objectives are to demonstrate that CCP decreases the viral load in nasopharyngeal swabs and increases the anti-SARS-CoV-2 antibody titre in recipients. TRIAL DESIGN: This is a randomized, open-label, parallel group, phase II/III study with a superiority framework. The trial starts with a screening phase II designed with two-tailed alpha=0.2. In case of positive results, the trial will proceed in a formally comparative phase III (alpha=0.05). PARTICIPANTS: Adult patients with confirmed or suspected COVID-19 who are at risk according to CDC definition are eligible. Inclusion criteria are all the following: age ≥ 65; pneumonia at CT scan; PaO2/FiO2 ≥300 mmHg; presence of one or more comorbidities; signed informed consent. Exclusion criteria are one of the following: age < 65; PaO2/FiO2 < 300 mmHg; pending cardiopulmonary arrest; refusal to blood product transfusions; severe IgA deficiency; any life-threatening comorbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion. The trial is being conducted at three reference COVID-19 centres in the middle of Italy. INTERVENTION AND COMPARATOR: Intervention: COVID-19 Convalescent Plasma (CCP) in addition to standard therapy. Patients receive three doses (200 ml/day on 3 consecutive days) of ABO matched CCP. Comparator: Standard therapy MAIN OUTCOMES: A. Primary outcome for Phase II: Proportion of patients without progression in severity of pulmonary disease, defined as worsening of 2 points in the ordinal scale of WHO by day 14. B. Primary outcome for Phase III: Proportion of patients without progression in severity of pulmonary disease, defined as worsening of 2 points in the ordinal scale of WHO by day 14. Secondary outcomes for Phase III: Decreased viral load on nasopharyngeal swab at days 6, 9 and 14; Decreased viremia at days 6 and 9; Increased antibody titer against SARS-CoV2 at days 30 and 60; Proportion of patients with negative of SARS-CoV2 nasopharyngeal swab at day 30; Length of hospital stay; Mortality rate at day 28; Total plasma related adverse event (day 60); Total non-plasma related adverse events (day 60); Severe adverse events (SAE) (day 60). RANDOMISATION: Treatment allocation is randomized with a ratio 1:1 in both phase II and phase III. Randomization sequences will be generated at Fondazione Policlinico Gemelli IRCCS through the RedCap web application. Randomized stratification is performed according to age (under/over 80 years), and sex. BLINDING (MASKING): None, this is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Phase II: 114 patients (57 per arm). Phase III: 182 patients (91 per arm) TRIAL STATUS: The trial recruitment started on May 27, 2020. The anticipated date of recruitment completion is April 30, 2021. The protocol version is 2 (May 10, 2020). TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov (May 5, 2020). The Identifier number is NCT04374526 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Betacoronavirus/genetics , Blood Transfusion/methods , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Aged , Aged, 80 and over , Betacoronavirus/immunology , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Progression , Female , Humans , Immunization, Passive/adverse effects , Immunization, Passive/methods , Informed Consent/ethics , Italy/epidemiology , Male , Mortality/trends , Pandemics , Pneumonia/diagnostic imaging , Pneumonia/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Viral Load/immunology , Viral Load/statistics & numerical data
14.
Nutr Metab Cardiovasc Dis ; 30(11): 1899-1913, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-759219

ABSTRACT

BACKGROUND AND AIMS: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. METHODS AND RESULTS: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. CONCLUSIONS: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.


Subject(s)
Betacoronavirus , Cardiovascular Diseases/etiology , Coronavirus Infections/mortality , Hospital Mortality , Machine Learning , Pneumonia, Viral/mortality , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , C-Reactive Protein/analysis , COVID-19 , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2 , Survival Analysis , Young Adult
15.
PLoS One ; 15(9): e0238414, 2020.
Article in English | MEDLINE | ID: covidwho-742541

ABSTRACT

In the face of the rapid evolution of the COVID-19 pandemic, healthcare professionals on the frontline are in urgent need of frequent updates in the accomplishment of their practice. Hence, clinicians started to search for prompt, valid information on sources that are parallel to academic journals. Aim of this work is to investigate the extent of this phenomenon. We administered an anonymous online cross-sectional survey to 645 Italian clinicians. Target of the survey were all medical figures potentially involved in the management of COVID-19 cases. 369 questionnaires were returned. 19.5% (n = 72) of respondents were younger than 30 years-old; 49,3% (n = 182) worked in Infectious Diseases, Internal Medicine or Respiratory Medicine departments, 11.5% (n = 42) in Intensive Care Unit and 7.4% (n = 27) were general practitioner. 70% (n = 261) of respondents reported that their use of social media to seek medical information increased during the pandemic. 39.3% (n = 145) consistently consulted Facebook groups and 53.1% (n = 196) Whatsapp chats. 47% (n = 174) of respondents reported that information shared on social media had a consistent impact on their daily practice. In the present study, we found no difference in social media usage between age groups or medical specialties. Given the urgent need for scientific update during the present pandemic, these findings may help understanding how clinicians access new evidences and implement them in their daily practice.


Subject(s)
Coronavirus Infections/epidemiology , Health Information Exchange/statistics & numerical data , Health Personnel/statistics & numerical data , Information Dissemination , Pneumonia, Viral/epidemiology , Social Media/statistics & numerical data , Adult , Age Factors , Aged , COVID-19 , Coronavirus Infections/psychology , Diffusion of Innovation , Female , Health Personnel/psychology , Humans , Italy , Male , Middle Aged , Pandemics , Pneumonia, Viral/psychology
16.
Br J Haematol ; 191(2): 207-211, 2020 10.
Article in English | MEDLINE | ID: covidwho-652703

ABSTRACT

A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the coronavirus disease 2019 (COVID-19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD-1 expression on both CD4+ T and CD8+ T cells in 42 COVID-19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of naive events. Our results might suggest a shift to antigen-activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID-19 infection.


Subject(s)
CD4-Positive T-Lymphocytes/chemistry , CD8-Positive T-Lymphocytes/chemistry , COVID-19/immunology , Lymphocyte Subsets/chemistry , Lymphopenia/etiology , Programmed Cell Death 1 Receptor/blood , fas Receptor/blood , Adult , Aged , Aged, 80 and over , Aging/blood , Aging/immunology , Apoptosis , COVID-19/blood , COVID-19/complications , Female , Humans , Lymphocyte Count , Male , Middle Aged , Prognosis , SARS-CoV-2
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