The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate.

Despite extensive studies into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the effect of maternal infection on the neonate is unclear. To investigate this, we characterized the immunology of neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy. Here we show that maternal SARS-CoV-2 infection affects the neonatal immune system. Despite similar proportions of B cells, CD4+ T cells and CD8+ T cells, increased percentages of natural killer cells, Vδ2+ γδ T cells and regulatory T cells were detected in neonates born to mothers with recent or ongoing infection compared with those born to recovered or uninfected mothers. Increased plasma cytokine levels were also evident in neonates and mothers within the recent or ongoing infection group. Cytokine functionality was enhanced in neonates born to SARS-CoV-2-exposed mothers, compared to those born to uninfected mothers. In most neonates, this immune imprinting was nonspecific, suggesting vertical transmission of SARS-CoV-2 is limited, a finding supported by a lack of SARS-CoV-2-specific IgM in neonates despite maternal IgG transfer.

Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19.

Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) ß and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRß and TCRδ loci, including some TCRß sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.

Ongoing mumps outbreak among adolescents and young adults, Ireland, August 2018 to January 2020.

Between 18 August 2018 and 24 January 2020, 3,736 mumps cases were notified in Ireland. The highest numbers of notifications were observed in the age group 15-24 years. Vaccination status was reported for 32% (n = 1,199) of cases: 72% of these had received two doses of measles-mumps-rubella (MMR) vaccine. Vaccination uptake after free MMR vaccination targeting colleges and universities since early 2019 was low. Therefore, a national media campaign began in January 2020.

Inpatient dermatology consultation aids diagnosis of cellulitis among hospitalized patients: A multi-institutional analysis.

BACKGROUND: Given its nonspecific physical examination findings, accurately distinguishing cellulitis from a cellulitis mimicker (pseudocellulitis) is challenging. OBJECTIVE: We sought to investigate the national incidence of cellulitis misdiagnosis among inpatients. METHODS: We conducted a retrospective review of inpatient dermatology consultations at Massachusetts General Hospital, University of Alabama at Birmingham Medical Center, University of California Los Angeles Medical Center, and University of California San Francisco Medical Center in 2008. All consults requested for the evaluation of cellulitis were included. The primary outcomes were determining the incidence of cellulitis misdiagnosis, evaluating the prevalence of associated risk factors, and identifying common pseudocellulitides. RESULTS: Of the 1430 inpatient dermatology consultations conducted in 2008, 74 (5.17%) were requested for the evaluation of cellulitis. In all, 55 (74.32%) patients evaluated for cellulitis were given a diagnosis of pseudocellulitis. There was no statistically significant difference in the rate of misdiagnosis across institutions (P = .12). Patient demographics and associated risk factor prevalence did not statistically vary in patients given a diagnosis of cellulitis versus those with pseudocellulitis (P > .05). LIMITATIONS: This study was unable to evaluate all patients admitted with cellulitis and was conducted at tertiary care centers, which may affect the generalizability of the results. CONCLUSIONS: Cellulitis is commonly misdiagnosed in the inpatient setting. Involving dermatologists may improve diagnostic accuracy and decrease unnecessary antibiotic use.

A survey assessment of the recognition and treatment of psychocutaneous disorders in the outpatient dermatology setting: how prepared are we?

BACKGROUND: Dermatologists provide the bulk of psychocutaneous care; however, recent studies suggest that dermatologists believe they are largely underprepared to treat most psychocutaneous conditions. OBJECTIVE: We sought to identify gaps in psychodermatologic knowledge among practicing dermatologists in two academic institutions. METHODS: An online survey was sent to 59 dermatologists at the Massachusetts General Hospital (Boston, MA) and Brigham and Women's Hospital (Boston, MA) from July 2010 through October 2011. RESULTS: The response rate was 40 of 59 (68%). More than 50% of dermatologists were comfortable making diagnoses for 8 of 10 psychocutaneous disorders. In all, 57% were comfortable making a diagnosis of depression. A total of 11% were comfortable starting antidepressants; 3%, antipsychotics; and 66%, medications for neuropathic pain. In all, 72%, 68%, and 21% of dermatologists never prescribe antidepressants, antipsychotics, or medications for neuropathic pain, respectively. Only 38% believed they were successful treating compulsive skin picking; 15%, body dysmorphic disorder; 27%, delusions of parasitosis; and 24%, depression. LIMITATIONS: Limitations include small sample size, data extraction from an academic setting, self-reporting of outcome measures, and response bias. CONCLUSION: Although the majority of the physicians surveyed believed they were capable of diagnosing psychocutaneous disease, very few were comfortable starting psychotropics or thought they were successful treating such conditions.

Churg-Strauss syndrome presenting as scar reactivation: histopathologic features and an illustration of 'locus minoris resistentiae'.

We report a 33-year-old female with cutaneous involvement by Churg-Strauss syndrome confined to surgical scars that were obtained 13 years before. She presented to the emergency department with 2-day history of fever, night sweats, right-sided weakness, hoarseness and worsening asthma symptoms. She was found to have an eosinophilia and two sub-5-mm pulmonary nodules. The patient also reported that the scars on her right thumb, inner wrist and back had been swollen, red and painful for 2 days. Examination revealed tender, erythematous, well-healed edematous scars studded with small skin colored papules. She had no clinical findings that were classic for cutaneous vasculitis. A skin biopsy of a scar revealed perivascular and palisading granulomatous inflammation consisting of histiocytes and neutrophils with leukocytoclasia. Focal vascular injury was identified. Scattered tissue eosinophils were seen. Special stains were negative for infection. Thereafter, she was started on intravenous steroids, at which point the fever, pulmonary and cutaneous symptoms subsided. Although scar sarcoidosis is a well-described phenomenon, granulomatous inflammation and vasculitis seen in Churg-Strauss syndrome exclusively manifesting in well-healed surgical scars highlights the unique features seen in this case and draws attention to the concept of locus minoris resistentiae. This case also highlights how a skin biopsy in the setting of suspected systemic vasculitis can confirm the presence of vasculitis and/or granulomatous inflammation and obviate the need for more invasive, higher risk procedures such as lung biopsy.

Rapidly fatal multiorgan Langerhans cell histiocytosis in a neonate.

Multiorgan Langerhans cell histiocytosis (LCH) presenting in the neonatal period is associated with a poor prognosis. We report a 5-day-old neonate who presented at birth with diffuse cutaneous nodules and respiratory failure who received a postmortem diagnosis of LCH. We emphasize the importance of recognizing the cutaneous findings of this rare disease.

Two distinct viral infections complicating pemphigus foliaceus.

We describe a patient with pemphigus foliaceus who developed two distinct disseminated cutaneous viral infections. Our patient is an 83-year-old female with a recent diagnosis of pemphigus foliaceus, who presented with painful ulcerations while on corticosteroids. Histopathology examination revealed disseminated herpes simplex virus (HSV). Despite adequate treatment with anti-herpetic treatment, some ulcerations failed to heal. A second biopsy revealed the presence of cytomegalovirus (CMV). This was treated successfully with appropriate antiviral therapy. In patients with autoimmune bullous disease, the development of new skin pain or new constitutional symptoms, change in primary morphology, rapid disease progression, or failure to respond to appropriate therapies should prompt the clinician to consider a concurrent cutaneous viral infection. There should be a low threshold to perform ancillary tests, to re-biopsy, and in severe cases, to consider empiric treatment with antiviral treatment therapy and modification of immunosuppressive regimens.

Building bridges: Connecting sport marketing and critical social science research.

Recently, sport management scholars have called for researchers to critically evaluate the ways in which research questions and resulting contributions truly disrupt what is known, how it is known, why it is important to know, and for whom. Historically, sport marketing research has adapted traditional research approaches from the parent marketing discipline to sport. Yet, sport is a constantly evolving social and cultural phenomenon and a reliance on conventional theories, concepts, and methods can serve to crystalize the discourse in sport marketing in ways that may limit knowledge production. Responding to this call, we believe that sport marketing research has much to gain from engaging with critical social science assumptions, worldviews, and perspectives to examine complex issues in sport. We position this paper as a starting point for advancing the field of sport marketing in meaningful and impactful ways by offering two research propositions, each accompanied by four actional recommendations. We employ a particular focus on the marketing campaigns that activate and promote corporate partnerships in sport to frame our two propositions, which discuss (1) consumer culture theory and (2) the circuit of culture as two important frameworks that begin to build bridges between sport marketing and critical social science.

Activation of Lymphocytes in Healthy Neonates Within Hours of Birth.

It is now established that immune maturation occurs along a defined trajectory in the weeks and months after birth, but the immediate changes that occur within immune cells following birth is less clear. In this study, we monitored the immune profile of neonates via analysis of paired samples (n= 28) of cord blood and heel prick blood taken at varying times post term delivery by planned elective caesarean section. This paired approach accounted for the between-subject variability often observed over the first week of life. We identified rapid changes in immune cell populations within hours of birth. Specifically, we observed increased proliferation in effector T cells (but not regulatory T cells) that exhibited an increase in cytokine producing ability and also an increase in the percentage of CD3 T cells over this short time frame. This indicates that the mobilisation of the immune system is immediate post birth, presumably as a response to sudden exposure to the external environment, antigen or stress. Hence, immune development may start to occur more rapidly than previously proposed and as such, to study this trajectory, blood sampling should begin as soon after birth as possible.

Three dimensional and microphysiological bone marrow models detect in vivo positive compounds.

Micronucleus (MN) assessment is a valuable tool in safety assessment. However, several compounds are positive in the in vivo bone marrow (BM) MN assay but negative in vitro, reflecting that BM complexity is not recapitulated in vitro. Importantly, these compounds are not genotoxic; rather, drug-driven pharmacological-effects on the BM increase MN, however, without mechanistic understanding, in vivo positives stop drug-progression. Thus, physiologically-relevant BM models are required to bridge the gap between in vitro and in vivo. The current study aimed to investigate the utility of two human 3D BM models (fluidic and static) for MN assessment. MN induction following treatment with etoposide and Poly-ADP Ribose Polymerase inhibitor (PARPi) and prednisolone (negative in vitro, positive in vivo) was determined in 2D L5178Y and human BM cells, and the 3D BM models. Etoposide (0-0.070 µM) and PARPi (0-150 µM) induced MN in both 3D BM models indicating their utility for genotoxicity testing. Interestingly, PARPi treatment induced a MN trend in 3D more comparable to in vivo. Importantly, prednisolone (0-1.7 mM) induced MN in both 3D BM models, suggesting recapitulation of the in vivo microenvironment. These models could provide a valuable tool to follow up, and eventually predict, suspected pharmacological mechanisms, thereby reducing animal studies.

Acute Immune Signatures and Their Legacies in Severe Acute Respiratory Syndrome Coronavirus-2 Infected Cancer Patients.

Given the immune system's importance for cancer surveillance and treatment, we have investigated how it may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type, stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2, apparent from the resemblance of their immune signatures to those for COVID-19+ non-cancer patients. This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding. Furthermore, while recovered solid cancer patients' immunophenotypes resemble those of non-virus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care.

Developing an Arrayed CRISPR-Cas9 Co-Culture Screen for Immuno-Oncology Target ID.

Immunotherapies including PD-L1 blockade have shown remarkable increases in the T cell-directed antitumor response; however, efficacy is seen only in a minority of patients. Recently, pooled CRISPR-Cas9 knockout (CRISPRn) screens in tumor/immune co-culture systems have identified a number of genes that confer resistance to T cell killing in pathways including antigen presentation and cytokine signaling, providing insight into tumor mechanisms that cause resistance to immunotherapies. The development of an arrayed CRISPRn screen in a tumor/immune co-culture system would allow the identification of novel targets for immuno-oncology, characterization of hits from pooled screens, and multiple assay endpoints to be measured per gene. Here, a small-scale arrayed CRISPRn screen was successfully developed to investigate the effects on a co-culture of T cells and Cas9-expressing PC9 lung adenocarcinoma cells modified to express anti-CD3 antibody on the cell surface (PC9-OKT3 T cell system). A focused CRISPRn library was designed to target genes involved in known resistance mechanisms (including antigen presentation, cytokine signaling, and apoptosis) as well as genes involved in immune synapse interactions. The viability of PC9 cells was assessed in two-dimensional adherent co-cultures via longitudinal imaging analysis. Knockout of epidermal growth factor receptor (EGFR) and PLK1 in tumor cells cultured alone or with T cells resulted in increased tumor cell death, as expected, whereas knockout of the test gene ICAM1 showed subtle donor-specific resistance to T cell killing. Taken together, these data provide proof of concept for arrayed CRISPRn screens in tumor/immune co-culture systems and warrant further investigation of in vitro co-culture models.

A dynamic COVID-19 immune signature includes associations with poor prognosis.

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.

Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis.

A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01186-5.

Nonsurgical management of hyperhidrosis.

HH is a chronic disease that can have a significant negative impact on a patient's quality of life. Primarily involving the axillae, palms, soles, and face, patients who have primary focal HH seek medical advice often long after they have been living with functional and psychosocial disability for some time. For every affected area of HH and at every stage of disease severity, conservative measures should be exhausted before progressing to surgical options. Treatment should be particular to each individual patient and chosen based on disease severity, expectations for improvement, and disease location. Generally, the most conservative options with the fewest adverse effects are attempted first. These include topical therapy (primarily AlCl3-6H2O) and iontophoresis. Patients who are less likely to respond to these measures are those living with severe disease (HDSS score of three or four). A minimally invasive procedure, intradermal BTX injections have been shown to improve disease significantly in these patients. Serving as an intermediate between conservative therapy and invasive surgery, BTX has revolutionized the treatment of focal HH. In many large controlled studies, it has been proved to be safe, efficacious, quick acting, and long lasting. Although BTX-A is most commonly used and studied, preliminary studies of BTX-B have demonstrated its potential to ameliorate focal HH significantly. Oral medications such as glycopyrrolate can be tried alone at any point in treatment, or as a useful adjunct, but side effects are common and caution should be taken with high-risk patients. For all forms of HH, the desired outcome for treatment should be qualitative and quantitative and it is critical for physicians to assess the patient's improvement periodically and adjust therapy, based on these therapeutic landmarks.