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2.
Diagnostic Microbiology and Infectious Disease ; : 115635, 2022.
Article in English | ScienceDirect | ID: covidwho-1620620

ABSTRACT

Use of antigen tests for the diagnosis of COVID-19 has become widespread. The aim of this study was to evaluate the diagnostic accuracy of the nasopharyngeal rapid antigen diagnostic (RAD) immunoassay LumiraDx UK in an Emergency Department (ED). All patients admitted to our ED between November 11 and December 8, 2020 and had both a RAD test and a real-time-reverse-transcription-polymerase-chain-reaction (RT-PCR) test were enrolled. RAD was considered as the index test and RT-PCR test was used as the reference standard. Sensitivity, specificity, negative and positive predictive values and likelihood ratios were calculated with the 95% confidence interval. The sensitivity and specificity of RAD were 34.2% and 92.3%. Positive and negative likelihood ratio were 4.4 and 0.71. Our results demonstrate that the diagnostic accuracy of the LumiraDx RAD test is too low for routine use as a diagnostic method in the ED.

3.
Semin Respir Crit Care Med ; 42(6): 735-736, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1591801
4.
J Clin Med ; 10(24)2021 Dec 18.
Article in English | MEDLINE | ID: covidwho-1580661

ABSTRACT

A number of studies have highlighted important alterations of the lipid profile in COVID-19 patients. Besides the well-known atheroprotective function, HDL displays anti-inflammatory, anti-oxidative, and anti-infectious properties. The aim of this retrospective study was to assess the HDL anti-inflammatory and antioxidant features, by evaluation of HDL-associated Serum amyloid A (SAA) enrichment and HDL-paraoxonase 1 (PON-1) activity, in a cohort of COVID-19 patients hospitalized at the Cardiorespiratory COVID-19 Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan. COVID-19 patients reached very low levels of HDL-c (mean ± SD: 27.1 ± 9.7 mg/dL) with a marked rise in TG (mean ± SD: 165.9 ± 62.5 mg/dL). Compared to matched-controls, SAA levels were significantly raised in COVID-19 patients at admission. There were no significant differences in the SAA amount between 83 alive and 22 dead patients for all-cause in-hospital mortality. Similar findings were reached in the case of PON-1 activity, with no differences between alive and dead patients for all-cause in-hospital mortality. In conclusion, although not related to the prediction of in-hospital mortality, reduction in HDL-c and the enrichment of SAA in HDL are a mirror of SARS-CoV-2 positivity even at the very early stages of the infection.

6.
J Cyst Fibros ; 2021 Dec 13.
Article in English | MEDLINE | ID: covidwho-1562343

ABSTRACT

The prevalence of anti-SARS-CoV-2 antibodies in people with cystic fibrosis (CF) is largely unknown. We carried out a cross-sectional study between March and June 2021 with the aim of estimating the seroprevalence of anti-SARS-CoV-2 antibodies in two CF centres in Northern Italy. Total serum anti-SARS-CoV-2 (spike) antibodies levels were measured and values ≥0.8 U/mL were considered positive. Among 434 patients aged >12 years, 64 patients had a positive result (14.7%, 95% CI: 11.5-18.4), 36 (56.3%) without experiencing any COVID-19-related symptoms. Three out of 49 transplanted patients tested positive with an odds ratio for a positive result among transplanted as compared to non-transplanted patients of 0.35 (95% CI: 0.07-1.14). No significant differences were observed between sexes, age groups, socioeconomic status and lung disease severity. In conclusion, SARS-CoV-2 has infected a relatively high proportion of our patients but in most cases the infection was asymptomatic.

7.
Sci Rep ; 11(1): 22913, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1537333

ABSTRACT

Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases.

8.
Respir Med ; 190: 106674, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1487957

ABSTRACT

Influenza and pneumococcal disease represent a well-known burden on healthcare systems worldwide, as well as they still have an attributed morbidity and mortality, especially in elderly individuals and vulnerable populations. In the context of the ongoing pandemic of COVID-19, a series of considerations in favor of extensive influenza and pneumococcal vaccination campaign are emerging, including a possible reduction of hospital extra burden and saving of sanitary resources. In addition, recent studies have suggested that prior vaccinations towards non SARS-CoV-2 pathogens might confer some protection against COVID-19. In this paper the authors consider all factors in support of these hypotheses and provide a consensus statement to encourage influenza and pneumococcal vaccinations in targeted populations.

9.
Vaccines (Basel) ; 9(11)2021 Oct 22.
Article in English | MEDLINE | ID: covidwho-1481051

ABSTRACT

Immunization through vaccination is a milestone achievement that has made a tremendous contribution to public health. Historically, immunization programs aimed firstly to protect children, who were disproportionally affected by infectious diseases. However, vaccine-preventable diseases can have significant impacts on adult mortality, health, and quality of life. Despite this, adult vaccinations have historically been overlooked in favor of other health priorities, because their benefits to society were not well recognized. As the general population is aging, the issue of vaccination in older adults is gaining importance. In high-income countries, recommendations for the routine vaccination of older adults have been gradually introduced. The Italian National Immunization Plan is considered to be among the most advanced adult vaccination plans in Europe. However, available data indicate there is low adherence to vaccination recommendations in Italy. The COVID-19 pandemic has exposed the damage that can be caused by an infectious disease, especially among adults and individuals with comorbidities. The aim of this "Manifesto", therefore, is to provide an overview of the existing evidence on the value of adult vaccination, in the Italian context, with a call to action to healthcare providers and health authorities.

10.
J Fungi (Basel) ; 7(9)2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1403846

ABSTRACT

The occurrence of pulmonary fungal superinfection due to Aspergillus spp. in patients with COVID-19 is a well-described complication associated with significant morbidity and mortality. This can be related to a directed effect of the virus and to the immunosuppressive role of the therapies administered for the disease. Here, we describe the first case of pulmonary infection due to Mucorales occurring in a patient with a concomitant diagnosis of COVID-19-associated pulmonary aspergillosis.

11.
Microbiol Spectr ; 9(2): e0054921, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1381170

ABSTRACT

In one year of the coronavirus disease 2019 (COVID-19) pandemic, many studies have described the different metabolic changes occurring in COVID-19 patients, linking these alterations to the disease severity. However, a complete metabolic signature of the most severe cases, especially those with a fatal outcome, is still missing. Our study retrospectively analyzes the metabolome profiles of 75 COVID-19 patients with moderate and severe symptoms admitted to Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Lombardy Region, Italy) following SARS-CoV-2 infection between March and April 2020. Italy was the first Western country to experience COVID-19, and the Lombardy Region was the epicenter of the Italian COVID-19 pandemic. This cohort shows a higher mortality rate compared to others; therefore, it represents a unique opportunity to investigate the underlying metabolic profiles of the first COVID-19 patients in Italy and to identify the potential biomarkers related to the disease prognosis and fatal outcome. IMPORTANCE Understanding the metabolic alterations occurring during an infection is a key element for identifying potential indicators of the disease prognosis, which are fundamental for developing efficient diagnostic tools and offering the best therapeutic treatment to the patient. Here, exploiting high-throughput metabolomics data, we identified the first metabolic profile associated with a fatal outcome, not correlated with preexisting clinical conditions or the oxygen demand at the moment of diagnosis. Overall, our results contribute to a better understanding of COVID-19-related metabolic disruption and may represent a useful starting point for the identification of independent prognostic factors to be employed in therapeutic practice.


Subject(s)
Blood Chemical Analysis , COVID-19/epidemiology , COVID-19/mortality , Energy Metabolism/physiology , Metabolome/physiology , Aged , Aged, 80 and over , Biomarkers/blood , Comorbidity , Female , Humans , Italy/epidemiology , Male , Middle Aged , Prognosis , Retrospective Studies , SARS-CoV-2
12.
Sci Immunol ; 6(62)2021 08 10.
Article in English | MEDLINE | ID: covidwho-1352519

ABSTRACT

To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+ T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+ T lymphocytes, while CD4+ T cells were less expanded and skewed toward TCM and TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+ GZMB+ effector cells were clonally expanded both during the infection and post-infection, while CD8+ GZMK+ lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+ GZMB+ and GZMK+ subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+ T cell population with memory precursor-like features.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Host-Pathogen Interactions/immunology , Immunophenotyping , SARS-CoV-2/immunology , Transcriptome , Adult , Aged , Antibodies, Viral/immunology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Biomarkers , COVID-19/virology , Cell Plasticity/genetics , Cell Plasticity/immunology , Clonal Evolution/immunology , Female , Gene Expression Profiling , Humans , Immunoglobulin Isotypes/immunology , Immunologic Memory , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lymphocyte Count , Male , Middle Aged , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
13.
Infect Dis Ther ; 10(4): 1837-1885, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1333141

ABSTRACT

INTRODUCTION: The Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) constituted an expert panel for developing evidence-based guidance for the clinical management of adult patients with coronavirus disease 2019 (COVID-19) outside intensive care units. METHODS: Ten systematic literature searches were performed to answer ten different key questions. The retrieved evidence was graded according to the Grading of Recommendations Assessment, Development, and Evaluation methodology (GRADE). RESULTS AND CONCLUSION: The literature searches mostly assessed the available evidence on the management of COVID-19 patients in terms of antiviral, anticoagulant, anti-inflammatory, immunomodulatory, and continuous positive airway pressure (CPAP)/non-invasive ventilation (NIV) treatment. Most evidence was deemed as of low certainty, and in some cases, recommendations could not be developed according to the GRADE system (best practice recommendations were provided in similar situations). The use of neutralizing monoclonal antibodies may be considered for outpatients at risk of disease progression. For inpatients, favorable recommendations were provided for anticoagulant prophylaxis and systemic steroids administration, although with low certainty of evidence. Favorable recommendations, with very low/low certainty of evidence, were also provided for, in specific situations, remdesivir, alone or in combination with baricitinib, and tocilizumab. The presence of many best practice recommendations testified to the need for further investigations by means of randomized controlled trials, whenever possible, with some possible future research directions stemming from the results of the ten systematic reviews.

14.
Chest ; 159(6): 2507-2508, 2021 06.
Article in English | MEDLINE | ID: covidwho-1251066
15.
Eur J Clin Invest ; 51(9): e13629, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1286672

ABSTRACT

Background During COVID-19 outbreak, Italy was the first country in Europe to be heavily affected with an intensive care unit mortality of 26%. In order to reduce this percentage, physicians should establish clear and objective criteria to stratify COVID-19 patients at high risk of in-hospital death. Thus, the aim has been to test a large spectrum of variables ranging from clinical evaluation to laboratory biomarkers to identify which parameter would best predict all-cause in-hospital mortality in COVID-19 patients. Design observational study. Results Multivariate Cox regression analysis showed that each 5 years of increase in age corresponded to a hazard ratio (HR) of 1.28 (95% CI 1.00-1.65, P = .050); each increment of 803 ng/L of N-terminal pro-B-type natriuretic peptide (NT-proBNP) corresponded to a HR of 1.24 (95% CI 1.11-1.39, P < .001); each increment of 58 ng/L of interleukin (IL)-6 corresponded to a HR of 1.23 (95% CI 1.09-1.40, P < .001), and each increment of 250 U/L of lactate dehydrogenase (LDH) corresponded to a HR of 1.23 (95% CI 1.10-1.37, P < .001). According to the calculated cut-points for age (≥70 years), NT-proBNP (≥803 ng/L), IL-6 (≥58 ng/L) and LDH (≥371 U/L) when 2 out of these 4 were overcome, the HR was 2.96 (95% CI 1.97-4.45, P < .001). Conclusion In COVID-19 patients, besides age, the evaluation of three biochemical parameters, available in few hours after hospital admission can predict in-hospital mortality regardless of other comorbidities.


Subject(s)
COVID-19/mortality , Hospital Mortality , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Age Factors , Aged , Biomarkers , COVID-19/blood , Female , Humans , Italy , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , SARS-CoV-2
16.
Eur J Intern Med ; 91: 59-62, 2021 09.
Article in English | MEDLINE | ID: covidwho-1284061

ABSTRACT

BACKGROUND: In the emergency department (ED) definitive diagnosis of SARS-COV-2 pneumonia is challenging as nasopharyngeal swab (NPS) can give false negative results. Strategies to reduce false negative rate of NPS have limitations. Serial NPSs (24-48 h from one another) are time-consuming, sputum can not be collected in the majority of patients, and bronchoalveolar lavage (BAL), the most sensitive test, requires specific expertise. Laryngotracheal aspiration (LTA) is easy to perform and showed a similar accuracy to BAL for diagnosis of other pulmonary diseases, however it was not studied to diagnose SARS-COV-2 pneumonia. OBJECTIVE: An observational cross-sectional study was performed to evaluate the negative predictive value of LTA in patients with suspected SARS-COV-2 pneumonia despite a negative NPS. METHODS: In the EDs of two university hospitals, consecutive patients with suspected SARS-COV-2 pneumonia despite a negative NPS underwent LTA performed with a nasotracheal tube connected to a vacuum system. Final diagnosis based on all respiratory specimen tests (NPS, LTA and BAL) and hospital data was established by two reviewers and in case of discordance by a third reviewer. RESULTS: 117 patients were enrolled. LTA was feasible in all patients and no patients experienced adverse events. Fifteen (12.7%) patients were diagnosed with community-acquired SARS-COV-2 pneumonia: 13 LTA positive and only 2 (1.7%) LTA negative. The negative predictive value of NPS and LTA was 87.3% (79.9% - 92.7%) and 98.1% (93.3%99.8%) respectively. CONCLUSIONS: LTA resulted feasible, safe and reduced false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative NPS.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Cross-Sectional Studies , False Negative Reactions , Humans , Larynx/virology , Nasopharynx , SARS-CoV-2/isolation & purification , Sputum , Trachea/virology
18.
Respir Med ; 180: 106355, 2021.
Article in English | MEDLINE | ID: covidwho-1118652

ABSTRACT

Non-pharmacological interventions and tracing-testing strategy proved insufficient to reduce SARS-CoV-2 spreading worldwide. Several vaccines with different mechanisms of action are currently under development. This review describes the potential target antigens evaluated for SARS-CoV-2 vaccine in the context of both conventional and next-generation platforms. We reported experimental data from phase-3 trials with a focus on different definitions of efficacy as well as factors affecting real-life effectiveness of SARS-CoV-2 vaccination, including logistical issues associated to vaccine availability, delivery, and immunization strategies. On this background, new variants of SARS-CoV-2 are discussed. We also provided a critical view on vaccination in special populations at higher risk of infection or severe disease as elderly people, pregnant women and immunocompromised patients. A final paragraph addresses safety on the light of the unprecedented reduction of length of the vaccine development process and faster authorization.


Subject(s)
COVID-19 Vaccines/pharmacology , COVID-19/prevention & control , Immunity, Herd , SARS-CoV-2/immunology , Vaccination/methods , COVID-19/epidemiology , COVID-19/immunology , Humans , Pandemics
19.
Thromb Haemost ; 121(8): 1087-1096, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1066018

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, which may dysregulate platelet function. Total Thrombus-Formation Analysis System (T-TAS) is a flow-chamber device that analyses platelet-mediated thrombus formation in capillary channels through the following parameters: (1) the area under the flow-pressure curve (AUC), (2) occlusion start time (OST), time needed to reach OST, and (3) occlusion time (OT), time needed to reach the occlusion pressure. METHODS AND FINDINGS: Sixty-one COVID-19 patients admitted to intensive, subintensive, and low intensive care were prospectively enrolled according to the time of admission: group A (up to 8 days) (n = 18); group B (from 9 to 21 days) (n = 19), and group C ( > 21 days) (n = 24). T-TAS measurements were performed at enrolment and after 7 days. Median OST was similar among groups. AUC was lower in group A compared to B (p = 0.001) and C (p = 0.033). OT was longer in group A compared to B (p = 0.001) and C (p = 0.028). Platelet count (PC) was higher in group B compared to A (p = 0.024). The linear regression showed that OT and AUC were independent from PC in group A (OT: 0.149 [95% confidence interval [CI]: -0.326 to 0.624], p = 0.513 and AUC: 0.005 [95% CI: -0.008 to 0.017], p = 0,447). In contrast, in group B, PC was associated with OT (-0.019 [-0.028 to 0.008], p = 0.023) and AUC (0.749 [0.358-1.139], p = 0,015), similarly to group C. Conversely, patients with different illness severity had similar T-TAS parameters. CONCLUSION: COVID-19 patients display an impaired platelet thrombus formation in the early phase of the disease compared to later stages and controls, independently from illness severity.


Subject(s)
Blood Platelets/pathology , COVID-19/complications , Thrombosis/etiology , Adult , Blood Coagulation , COVID-19/blood , COVID-19/pathology , Female , Humans , Male , Middle Aged , Platelet Function Tests , Prospective Studies , Thrombosis/blood , Thrombosis/pathology , Young Adult
20.
Radiol Med ; 126(5): 722-728, 2021 May.
Article in English | MEDLINE | ID: covidwho-1037984

ABSTRACT

BACKGROUND: Preliminary reports suggest a hypercoagulable state in COVID-19. Deep vein thrombosis (DVT) is perceived as a frequent finding in hospitalized COVID-19 patients, but data describing the prevalence of DVT are lacking. OBJECTIVES: We aimed to report the prevalence of DVT in COVID-19 patients in general wards, blinded to symptoms/signs of disease, using lower extremities duplex ultrasound (LEDUS) in random patients. We tested the association of DVT with clinical, laboratory and inflammatory markers and also reported on the secondary endpoint of in-hospital mortality. PATIENTS/METHODS: n  = 263 COVID-19 patients were screened with LEDUS between March 01, 2020 and April 05, 2020 out of the overall n = 1012 admitted with COVID-19. RESULTS: DVT was detected in n = 67 screened patients (25.5%), n = 41 patients (15.6%) died during the index hospitalization. Multiple logistic regression demonstrated that only C-reactive protein (odds ratio 1.009, 95% CI 1.004-1.013, p < 0.001) was independently associated with the presence of DVT at LEDUS. Both age (odds ratio 1.101, 95% CI 1.054-1.150, p < 0.001) and C-reactive protein (odds ratio 1.012, 95% CI 1.006-1.018, p < 0.001) were instead significantly independently associated with in-hospital mortality. CONCLUSIONS: The main study finding is that DVT prevalence in COVID-19 patients admitted to general wards is 25.5%, suggesting it may be reasonable to screen COVID-19 patients for this potentially severe but treatable complication, and that inflammation, measured with serum C-reactive protein, is the main variable associated with the presence of DVT, where all other clinical or laboratory variables, age or D-dimer included, are instead not independently associated with DVT.


Subject(s)
COVID-19/complications , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology , Aged , COVID-19 Testing , Cross-Sectional Studies , Female , Hospitals , Humans , Lower Extremity/diagnostic imaging , Male , Middle Aged , Prevalence , Ultrasonography, Doppler, Duplex , Venous Thrombosis/diagnosis
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