Multisystem inflammatory syndrome in children related to COVID-19: A New York City experience.

In December 2019, the 2019, a novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in Wuhan, China. This has now spread worldwide and was declared a pandemic by March 2020. Initially, the pediatric population was described as a low risk for severe COVID-19. However, reports have emerged recently of cases of COVID-19 in children with a systemic inflammatory disease, with features that overlap with Kawasaki disease (KD). We describe the first 15 cases with the multi-systeminflammatory syndrome in children (MIS-C), temporally related to COVID-19, who presented for care to a tertiary pediatric referral center in New York City. We discuss the disproportionate burden of disease among Hispanic/Latino and Black/African American ancestry, the distinct cytokine signature across the disease spectrum (IL-1/IL-6), and the potential role and pathogenesis of SARS-CoV-2 in this new clinical entity.

Streptococcus pneumoniae purulent pericarditis in a neonate.

Purulent bacterial pericarditis is an uncommon infection that manifests during childhood, and in the post-antibiotic era Streptococcus pneumoniae is an unusual cause.We report a case of purulent bacterial pericarditis in a neonate caused by Streptococcus pneumoniae serotype 7F. Although cases of bacterial pericarditis caused by Streptococcus pneumoniae as a causative agent have been reported, their combination in a neonate is unique and this is, to our knowledge, the first case of this combination in the newborn period.

Falsely Undetectable Vancomycin Levels in a Pediatric Patient With Chronic Granulomatous Disease.

A child with chronic granulomatous disease on vancomycin treatment had V trough levels that became undetectable, as measured in our hospital's clinical laboratory by a commonly employed particle-enhanced turbidometric inhibition assay. An alternative laboratory method yielded appropriate results. Recognizing and resolving erroneously low V trough levels could prevent needless adjustments in dosing that could increase risk for acute kidney injury.

Hate versus politics: detection of hate against policy makers in Italian tweets.

Accurate detection of hate speech against politicians, policy making and political ideas is crucial to maintain democracy and free speech. Unfortunately, the amount of labelled data necessary for training models to detect hate speech are limited and domain-dependent. In this paper, we address the issue of classification of hate speech against policy makers from Twitter in Italian, producing the first resource of this type in this language. We collected and annotated 1264 tweets, examined the cases of disagreements between annotators, and performed in-domain and cross-domain hate speech classifications with different features and algorithms. We achieved a performance of ROC AUC 0.83 and analyzed the most predictive attributes, also finding the different language features in the anti-policymakers and anti-immigration domains. Finally, we visualized networks of hashtags to capture the topics used in hateful and normal tweets.

Postnatal maturation of total cell content and up-regulated surface expression of Mac-1 (CD11b/CD18) in polymorphonuclear leukocytes of human infants.

Markedly deficient expression of membrane-activated complex 1 (Mac-1; CD11b/CD18) by polymorphonuclear neutrophils (PMN) of human neonates compared with adults is well documented. To define postnatal maturation of Mac-1 expression of PMN, lysates of PMN from 21 infants, aged 1-14 months, and concurrent adult controls were assayed by ELISA for total cell content of Mac-1 and LFA-1 (CD11a/CD18), and LFA-1 content was within the normal adult range at all ages tested. Mac-1 content was approximately 50% of adult levels for infants 1-2 months of age and steadily increased to reach normal adult levels by 11-12 months of age. For a separate group of 25 infants, aged 0.5-11 months, measurement of surface expression of Mac-1 and LFA-1 on activated PMN by immunofluorescence flow cytometry yielded results that were similar to those obtained by ELISA.

Maternal-infant perinatal transmission of methicillin-resistant and methicillin-sensitive Staphylococcus aureus.

Because of the increasing importance of Staphylococcus aureus (SA), including methicillin-resistant SA (MRSA) in serious neonatal infections, we studied the contribution of perinatal maternal-infant transmission of SA to the colonization and infection of newborn infants. Cultures for SA, including MRSA, were obtained from nares and vagina of women in labor at term. Each mother's infant, if delivered vaginally, was cultured from nares and skin at delivery and again after 48 hours (at discharge). All MRSA and selected SA isolates were studied by pulsed field gel electrophoresis (PFGE). Infants were monitored after discharge for staphylococcal infection for 4 weeks. Of 304 women completing the study, 43 were colonized with SA, and 9/43 had MRSA. Of 252 evaluable infants, 25 were colonized with SA, and 9/25 had MRSA. Six of 252 mother-infant pairs were concordant for SA colonization, and one of these for MRSA. Isolates from five of these six infants were indistinguishable from their mother's isolates by PFGE, including the pair with MRSA. One SA-colonized infant and four noncolonized infants subsequently developed staphylococcal infections during the monitoring period. About 20% of SA isolates in this maternal population were MRSA. Perinatal maternal-infant transmission accounted for 20% of instances of perinatal colonization of infants with SA. Molecular confirmation of perinatal maternal-infant transmission of MRSA was first documented. In this population of term infants, most SA infections in the first 4 weeks of life appeared to result from colonization that occurred after discharge from the nursery.

The murine myeloid cell line 32Dcl3 as a model system for studying neutrophil functions.

The murine myeloid cell line 32Dcl3 is one of the few cell lines that can terminally differentiate into neutrophils. Granulocyte colony-stimulating factor (G-CSF) drives the differentiation of these cells; therefore, G-CSF receptor signaling for neutrophil proliferation and differentiation has been studied extensively using this cell line as a model. Differentiated 32Dcl3 cells exhibit a striking morphologic similarity to normal neutrophils; however, the degree to which differentiated 32Dcl3 cells are functionally similar to normal neutrophils remains unknown. In this study, we compared the function of differentiated 32Dcl3 cells with mouse neutrophils. Our results demonstrate that a subclone of differentiated 32Dcl3 cells (32Dcl3C) exhibits normal neutrophil functions of phagocytosis, degranulation, adhesion and shape change in response to appropriate stimuli. These observations suggest that this cell line can serve as an effective model system to study similar mature neutrophil functions. However, 32Dcl3C cells fail to produce superoxide in response proper stimuli.

A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans.

Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteopetrosis at an early age. These symptoms are consistent with but more severe than those reported for people with leukocyte adhesion deficiency III (LAD-III). Mechanistically, these symptoms arose from an inability to activate the integrins expressed on hematopoietic cells, including platelets and leukocytes. Immortalized lymphocyte cell lines isolated from the two individuals showed integrin activation defects. Several proteins previously implicated in integrin activation, including Ras-associated protein-1 (RAP1) and calcium and diacylglycerol-regulated guanine nucleotide exchange factor-1 (CALDAG-GEF1), were present and functional in these cell lines. The genetic basis for this disease was traced to a point mutation in the coding region of the KINDLIN3 (official gene symbol FERMT3) gene. When wild-type KINDLIN-3 was expressed in the immortalized lymphocytes, their integrins became responsive to activation signals. These results identify a genetic disease that severely compromises the health of the affected individuals and establish an essential role of KINDLIN-3 in integrin activation in humans. Furthermore, allogeneic bone marrow transplantation was shown to alleviate the symptoms of the disease.

Innate immune responses to infection.

The human host survives many infectious challenges in the absence of preexisting specific (adaptive) immunity because of the existence of a separate set of protective mechanisms that do not depend on specific antigenic recognition. These antigen-independent mechanisms constitute innate immunity. Antimicrobial peptides are released at epithelial surfaces and disrupt the membranes of many microbial pathogens. Toll-like receptors on epithelial cells and leukocytes recognize a range of microbial molecular patterns and generate intracellular signals for activation of a range of host responses. Cytokines released from leukocytes and other cells exhibit a vast array of regulatory functions in both adaptive and innate immunity. Chemokines released from infected tissues recruit diverse populations of leukocytes that express distinct chemokine receptors. Natural killer cells recognize and bind virus-infected host cells and tumor cells and induce their apoptosis. Complement, through the alternative and mannose-binding lectin pathways, mediates antibody-independent opsonization, phagocyte recruitment, and microbial lysis. Phagocytes migrate from the microcirculation into infected tissue and ingest and kill invading microbes. These innate immune mechanisms and their interactions in defense against infection provide the host with the time needed to mobilize the more slowly developing mechanisms of adaptive immunity, which might protect against subsequent challenges.

Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1.

Two novel CD18 mutations were identified in a patient who was a compound heterozygote with type 1 leukocyte adhesion deficiency and whose phenotype was typical except that he exhibited hypertrophic scarring. A deletion of 36 nucleotides in exon 12 (1622del36) predicted the net loss of 12 amino acid (aa) residues in the third cysteine-rich repeat of the extracellular stalk region (mut-1). A nonsense mutation in exon 15 (2200G>T), predicted a 36-aa truncation of the cytoplasmic domain (mut-2). Lymphocyte function-associated antigen 1 (LFA-1) and macrophage antigen-1 (Mac-1) containing the mut-1 beta(2) subunit were expressed at very low levels compared with wild-type (wt) beta(2). Mac-1 and LFA-1 expression with the mut-2 beta(2) subunit were equivalent to results with wt beta(2). Binding function of Mac-1 with mut-2 beta(2) was equivalent to that with wt beta(2). However, binding function of LFA-1 with the mut-2 beta(2) subunit was reduced by 50% versus wt beta(2). It was concluded that (1) the portion of the CD18 stalk region deleted in mut-1 is critical for beta(2) integrin heterodimer expression but the portion of the cytoplasmic domain truncated in mut-2 is not; and (2) the mut-2 cytoplasmic domain truncation impairs binding function of LFA-1 but not of Mac-1. Studies with the patient's neutrophils (PMNs) were consistent with functional impairment of LFA-1 but not of Mac-1.