We described the case of a patient affected by activated PI3K-kinase delta syndrome (APDS) and a long-lasting and pauci-symptomatic SARS-CoV-2 infection, treated with multiple therapeutic agents ...including remdesivir and SARS-CoV-2-neutralizing monoclonal antibodies. We detected the clearance of the virus 105 days from the first positive swab and 7 days after monoclonal antibody administration. At genotyping, the SARS-CoV-2 virus resulted as wild type on all samples tested. This case shows the monoclonal antibodies’ good tolerability and efficacy in reducing viral shedding in long-lasting infections refractory to other treatments.
Background
Although SARS‐CoV‐2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti‐SARS‐CoV‐2 ...immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti‐SARS‐CoV‐2 immunity in children with distinct symptomatology.
Methods
Between March and July 2020, we recruited 15 SARS‐CoV‐2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS‐CoV‐2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti‐SARS‐CoV‐2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen‐specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink.
Results
Virological profiling showed that AS patients had lower viral load at diagnosis (p = .004) and faster virus clearance (p = .0002) compared with SY patients. Anti‐SARS‐CoV‐2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS‐CoV‐2 IgG, levels of neutralizing activity, and frequency of Ag‐specific B and CD8+ T cells, whereas pro‐inflammatory plasma protein profile was found to be associated with symptomatology.
Conclusion
We demonstrated the development of anti‐SARS‐CoV‐2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance.
The hyper‐inflammatory response, also known as multisystem inflammatory syndrome in children (MIS‐C), represents a major concern in children with SARS‐CoV‐2 infection. We report bone marrow features ...of three patients with MIS‐C who were diagnosed during the first wave of the SARS‐CoV‐2 pandemic. A bone marrow evaluation was performed at onset of the inflammatory condition in order to exclude secondary hemophagocytic lymphohistiocytosis (sHLH). The bone marrows of the patients presented common features: the erythroid and megakaryocytic lineages were prominently affected and hemophagocytosis was moderately increased, differently than observed in sHLH. Megakaryocytopoiesis was increased, representing a peculiar feature of MIS‐C differing from sHLH. SARS‐CoV‐2 RT‐PCR and viral panel were studied in bone marrow aspiration samples. MIS‐C is a rare complication of SARS‐CoV‐2 infections in children. An immuno‐dysregulation considering both innate and adaptive immunity together with vascular inflammation and endothelial dysfunction play a major role. Our observations, although limited due to the small sample size, suggest that there are unique features in the bone marrow of patients with MIS‐C that are likely secondary to immuno‐dysregulation, and there are notable differences in bone marrow features compared to those reported in sHLH.
Lately, one of the major clinical and public health issues has been represented by Coronavirus disease of 2019 (COVID-19) during pregnancy and the risk of transmission of the infection from mother to ...child. Debate on perinatal management and postnatal care is still ongoing, principally questioning the option of the joint management of mother and child after birth and the safety of breastfeeding. According to the available reports, neonatal COVID-19 appears to have a horizontal transmission and seems to be paucisymptomatic or asymptomatic, compared to older age groups. The aim of this work is to describe a cluster of neonatal COVID-19 and discuss our experience, with reference to current evidence on postnatal care and perinatal management.
This is a retrospective observational case series of five mother-child dyads, who attended the Labor and Delivery Unit of a first-level hospital in Italy, in March 2020. Descriptive statistics for continuous variables consisted of number of observations, mean and the range of the minimum and maximum values.
Five women and four neonates tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In one case, the mother-child dyad was separated and the neonate remained negative on two consecutive tests. Two positive neonates developed symptoms, with a predominant involvement of the gastrointestinal tract. Blood tests were unremarkable, except for a single patient who developed mild neutropenia. No complications occurred.
We agree that the decision on whether or not to separate a positive/suspected mother from her child should be made on an individual basis, taking into account the parent's will, clinical condition, hospital logistics and the local epidemiological situation. In conformity with literature, in our study, affected neonates were asymptomatic or paucisymptomatic. Despite these reassuring findings, a few cases of severe presentation in the neonatal population have been reported. Therefore, we agree on encouraging clinicians to monitor the neonates with a suspected or confirmed infection.
Aim: Up-regulation of soluble CD40 ligand (sCD40L) and of monocyte chemoattractant protein-1 (MCP-1) has been found in diabetes and in patients with acute cerebral ischemia. We asked whether (i) the ...two molecules are similarly upregulated among non-lacunar and lacunar diabetic strokes and (ii) sCD40L and/or MCP-1 predict the risk of cardiovascular events in this setting. Methods: Ninety patients with type 2 diabetes mellitus presenting with an acute ischemic stroke (compared with 45 control subjects) were evaluated on admission and up to 36 months (median 24 months) after the event. Results: Diabetic patients with acute stroke had higher plasma CD40L and MCP-1 than controls (p<0.0001), with no significant differences among lacunar and non-lacunar strokes. On multiple regression analysis, only higher sCD40L quartiles and older age were associated with higher MCP-1 quartiles. Forty-eight percent of patients experienced vascular events. Cox regression analysis showed that only the presence of higher sCD40L values independently predicted the recurrence of vascular events. Conclusion: Up-regulation of inflammatory molecules, such as CD40L and MCP-1, is involved in the advanced stage of atherosclerotic cerebro-vascular disease and is associated with increased risk of recurrence of cardiovascular events.
Background. Parkinson’s disease (PD) is mostly characterized by alpha-synuclein (SNCA) aggregation and loss of nigrostriatal dopamine-containing neurons. In this study a novel SNCA multiplication is ...described in two siblings affected by severe parkinsonism featuring early onset dyskinesia, psychiatric symptoms, and cognitive deterioration. Methods. SNCA dosage was performed using High-Density Comparative Genomic Hybridization Array (CGH-Array), Multiple Ligation Dependent Probe Amplification (MLPA), and Quantitative PCR (qPCR). Genetic analysis was associated with clinical evaluation. Results. Genetic analysis of siblings showed for the first time a 351 Kb triplication containing SNCA gene along with 6 exons of MMRN1 gene in 4q22.1 and a duplication of 1,29 Mb of a genomic region flanking the triplication. Conclusions. The identification of this family indicates a novel mechanism of SNCA gene multiplication, which confirms the genomic instability in this region and provides data on the genotype-phenotype correlation in PD patients.
Abstract Activated PI3-kinase delta syndrome (APDS) was recently reported as a novel primary immunodeficiency caused by heterozygous gain-of-function mutations in PIK3CD gene. Here we describe ...immunological studies in a 19 year old APDS patient for whom genetic diagnosis was discovered by Whole Exome Sequencing (WES) analysis. In addition to the progressive lymphopenia and defective antibody production we showed that the ability of the patient's B cells to differentiate in vitro is severely reduced. An in depth analysis of the myeloid compartment showed an increased expression of CD83 activation marker on monocytes and mono-derived DC cells. Moreover, monocytes-derived macrophages (MDMs) failed to solve the Mycobacterium bovis bacillus Calmette Guèrin (BCG) infection in vitro . Selective p110δ inhibitor IC87114 restored the MDM capacity to kill BCG in vitro. Our data show that the constitutive activation of Akt-mTOR pathway induces important alterations also in the myeloid compartment providing new insights in order to improve the therapeutic approach in these patients.
Biological sex and sociocultural gender matter when it comes to health and diseases. They have been both proposed as the undeniable gateways towards a personalized approach in care delivery. The ...Gender Working Group of the Italian Society of Internal Medicine (SIMI) was funded in 2019 with the aim of promoting good practice in the integration of sex and gender domains in clinical studies. Starting from a narrative literature review and based on regular meetings which led to a shared virtual discussion during the national SIMI congress in 2021, the members of the WG provided a core operational framework to be applied by internal medicine (IM) specialists to understand and implement their daily activity as researchers and clinicians. The SIMI Gender ‘5 Ws’ Rule for clinical studies has been conceptualized as follows: Who (Clinical Internal Medicine Scientists and Practitioners), What (Gender-related Variables—Gender Core Dataset), Where (Clinical Studies/Translational Research), When (Every Time It Makes Sense) and Why (Explanatory Power of Gender and Opportunities). In particular, the gender core dataset was identified by the following domains (variables to collect accordingly): relations (marital status, social support, discrimination); roles (occupation, caregiver status, household responsibility, primary earner, household dimension); institutionalized gender (education level, personal income, living in rural vs urban areas); and gender identity (validated questionnaires on personality traits). The SIMI Gender ‘5 Ws’ Rule is a simple and easy conceptual framework that will guide IM for the design and analysis of clinical studies.
PDF
