The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients' survival and long COVID.

Introduction: SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.

Methods: We longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19.

Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency.

Recombination activating genes () are tightly regulated during lymphoid differentiation, and their mutations cause a spectrum of severe immunological disorders. Hematopoietic stem and progenitor cell (HSPC) transplantation is the treatment of choice but is limited by donor availability and toxicity. To overcome these issues, we developed gene editing strategies targeting a corrective sequence into the human gene by homology-directed repair (HDR) and validated them by tailored two-dimensional, three-dimensional, and in vivo xenotransplant platforms to assess rescue of expression and function.

HOMA-IR and the Matsuda Index as predictors of progression to type 1 diabetes in autoantibody-positive relatives.

Aim/hypothesis: We assessed whether HOMA-IR and the Matsuda Index are associated with transitions through stages of type 1 diabetes.

Methods: Autoantibody (AAb)-positive relatives of individuals with type 1 diabetes (n=6256) from the TrialNet Pathway to Prevention were studied. Associations of indicators of insulin resistance (HOMA-IR) and insulin sensitivity (Matsuda Index) with BMI percentile (BMIp) and age were assessed with adjustments for measures of insulin secretion, Index60 and insulinogenic index (IGI).

Analysis of healthcare workers' mental health during the COVID-19 pandemic: Evidence from a three-wave longitudinal study.

The "Healthcare workers' wellbeing [Benessere Operatori]" project is an exploratory longitudinal study assessing healthcare workers' mental health at three different time points over a 14-month period during the COVID-19 pandemic. We collected socio-demographic and work-related information and assessed the perceived social support, coping strategies, and levels of depression, anxiety, insomnia, anger, burnout, and PTSD symptoms. In total, 325 Italian healthcare workers (i.

Modifiable risk factors of COVID-19 in patients with multiple sclerosis: a single-centre case-control study.

Background: Disease and treatment-associated immune system abnormalities may confer higher risk of Coronavirus disease 2019 (COVID-19) to people with multiple sclerosis (PwMS). We assessed modifiable risk factors associated with COVID-19 in PwMS.

Methods: Among patients referring to our MS Center, we retrospectively collected epidemiological, clinical and laboratory data of PwMS with confirmed COVID-19 between March 2020 and March 2021 (MS-COVID, n = 149).

Modelling the impact of protein-kinase R allelic variant on HIV biomarkers trajectories by means of latent class mixed models.

This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position -168 of the promoter region of the protein kinase R (-168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication.

The "Healthcare Workers' Wellbeing [Benessere Operatori]" Project: A Longitudinal Evaluation of Psychological Responses of Italian Healthcare Workers during the COVID-19 Pandemic.

Background: COVID-19 forced healthcare workers to work in unprecedented and critical circumstances, exacerbating already-problematic and stressful working conditions. The "Healthcare workers' wellbeing (Benessere Operatori)" project aimed at identifying psychological and personal factors, influencing individuals' responses to the COVID-19 pandemic.

Methods: 291 healthcare workers took part in the project by answering an online questionnaire twice (after the first wave of COVID-19 and during the second wave) and completing questions on socio-demographic and work-related information, the Depression Anxiety Stress Scale-21, the Insomnia Severity Index, the Impact of Event Scale-Revised, the State-Trait Anger Expression Inventory-2, the Maslach Burnout Inventory, the Multidimensional Scale of Perceived Social Support, and the Brief Cope.

Profiling Antibody Response Patterns in COVID-19: Spike S1-Reactive IgA Signature in the Evolution of SARS-CoV-2 Infection.

This contribution explores in a new statistical perspective the antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 141 coronavirus disease 2019 (COVID-19) patients exhibiting a broad range of clinical manifestations. This cohort accurately reflects the characteristics of the first wave of the SARS-CoV-2 pandemic in Italy. We determined the IgM, IgA, and IgG levels towards SARS-CoV-2 S1, S2, and NP antigens, evaluating their neutralizing activity and relationship with clinical signatures.

Exocrine pancreas function is impaired in adult relatives of patients with type 1 diabetes.

Aims: Alterations of the exocrine pancreas have been reported in type 1 diabetes, but their contribution to the pathogenesis of the disease is poorly understood. Here, we investigated markers of exocrine pancreas dysfunction in individuals at-risk of developing type 1 diabetes.

Methods: Serum P-amylase and lipase levels were assessed in samples obtained from healthy controls, patients with new onset type 1 diabetes, relatives participating to the TrialNet Pathway to Prevention who were, at blood collection, autoantibody negative or positive for a single autoantibody (low-risk individuals), and positive for multiple autoantibodies (high-risk individuals).

CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

Background: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment.

Methods: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism.

Saliva molecular testing for SARS-CoV-2: simplifying the diagnosis without losing accuracy.

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Deepening Well-Being Evaluation with Different Data Sources: A Bayesian Networks Approach.

In this paper, we focus on a Bayesian network s approach to combine traditional survey and social network data and official statistics to evaluate well-being. Bayesian networks permit the use of data with different geographical levels (provincial and regional) and time frequencies (daily, quarterly, and annual). The aim of this study was twofold: to describe the relationship between survey and social network data and to investigate the link between social network data and official statistics.

Metachromatic leukodystrophy: A single-center longitudinal study of 45 patients.

In this study, we characterize the natural course of metachromatic leukodystrophy (MLD), explore intra/inter group differences, and identify biomarkers to monitor disease progression. This is a longitudinal observational study. Genotype and characteristics at disease onset were recorded.

Psychological factors influencing emotional reactions to gestational trophoblastic disease: The role of coping mechanisms and illness perception.

Objective: Referring to Leventhal's common-sense model, this observational cross-sectional study aimed at investigating the relationship between illness mental representations, coping mechanisms and psychological distress in a sample of women with gestational trophoblastic disease (GTD).

Methods: Thirty-eight women diagnosed with GTD (18 with hydatidiform mole; 20 with gestational trophoblastic neoplasia) were asked to complete the Illness Perception Questionnaire-Revised, the Coping Orientation to the Problems Experienced, the State-Trait Anxiety Inventory-Form Y and the Beck Depression Inventory-Short Form. Demographic and clinical information was collected through a self-report questionnaire.

A New Model of Chronic Lung Infection in Immunocompetent Mice.

Pulmonary infections caused by (MA) have increased over recent decades, affecting individuals with underlying pathologies such as chronic obstructive pulmonary disease, bronchiectasis and, especially, cystic fibrosis. The lack of a representative and standardized model of chronic infection in mice has limited steps forward in the field of pulmonary infection. To overcome this challenge, we refined the method of agar beads to establish chronic infection in immunocompetent mice.

Theory of mind and loneliness: Effects of a conversation-based training at school.

Conversation-based training programmes are known to be effective in enhancing theory of mind (ToM). The possible consequences of such training programmes on the understanding of other constructs have rarely been investigated. The present research aimed to evaluate the effects of two different types of conversation-based training on ToM and loneliness.

Efficient gene editing of human long-term hematopoietic stem cells validated by clonal tracking.

Targeted gene editing in hematopoietic stem cells (HSCs) is a promising treatment for several diseases. However, the limited efficiency of homology-directed repair (HDR) in HSCs and the unknown impact of the procedure on clonal composition and dynamics of transplantation have hampered clinical translation. Here, we apply a barcoding strategy to clonal tracking of edited cells (BAR-Seq) and show that editing activates p53, which substantially shrinks the HSC clonal repertoire in hematochimeric mice, although engrafted edited clones preserve multilineage and self-renewing capacity.