Evidence-based public health approaches that minimize the introduction and spread of new SARS-CoV-2 transmission clusters are urgently needed in the United States and other countries struggling with ...expanding epidemics. Here we analyze 247 full-genome SARS-CoV-2 sequences from two nearby communities in Wisconsin, USA, and find surprisingly distinct patterns of viral spread. Dane County had the 12
known introduction of SARS-CoV-2 in the United States, but this did not lead to descendant community spread. Instead, the Dane County outbreak was seeded by multiple later introductions, followed by limited community spread. In contrast, relatively few introductions in Milwaukee County led to extensive community spread. We present evidence for reduced viral spread in both counties following the statewide "Safer at Home" order, which went into effect 25 March 2020. Our results suggest patterns of SARS-CoV-2 transmission may vary substantially even in nearby communities. Understanding these local patterns will enable better targeting of public health interventions.
Abstract
In a household study, loss of taste and/or smell was the fourth most reported symptom (26/42 62%) among coronavirus disease 2019 (COVID-19) case patients and had the highest positive ...predictive value (83% 95% confidence interval CI, 55%–95%) among household contacts. Olfactory and taste dysfunctions should be considered for COVID-19 case identification and testing prioritization.
Severe combined immunodeficiency is a life-threatening primary immune deficiency characterized by low numbers of naïve T cells. Early diagnosis and treatment of this disease decreases mortality. In ...2008, Wisconsin began newborn screening of infants for severe combined immunodeficiency and other forms of T-cell lymphopenia by the T-cell receptor excision circle assay. In total, 207,696 infants were screened. Seventy-two infants had an abnormal assay. T-cell numbers were normal in 38 infants, abnormal in 33 infants, and not performed in one infant, giving a positive predictive value for T-cell lymphopenia of any cause of 45.83% and a specificity of 99.98%. Five infants with severe combined immunodeficiency/severe T-cell lymphopenia requiring hematopoietic stem cell transplantation or other therapy were detected. In summary, the T-cell receptor excision circle assay is a sensitive and specific test to identify infants with severe combined immunodeficiency and severe T-cell lymphopenia that leads to life-saving therapies such as hematopoietic stem cell transplantation prior to the acquisition of severe infections.
In a mouse model of viral induced atopic disease, expression of FcεRI on dendritic cells is critical. While adult human conventional (cDC) and plasmacytoid (pDC) dendritic cells have been shown to ...express FcεRI, it is not known if this receptor is expressed in childhood and how its expression is governed by IgE.
Following informed consent of subjects (n = 27, aged 12-188 months), peripheral blood was stained for surface expression of CD19, ILT7, CD1c, IgE, FcεRI and analyzed by flow cytometry (cDC: CD19(-) ILT7(-) CD1c(+); pDC: CD19(-) ILT7(+) CD1c(-)). Total and specific serum IgE levels to food and inhalant allergens were determined by ImmunoCAP, and the relationship between FcεRI expression on dendritic cells and sensitization, free IgE, cell bound IgE, and age was determined.
Independent of sensitization status, FcεRI expression was noted on cDC and pDC as early as 12 months of age. Serum IgE level correlated with expression of FcεRI on cDC, but not pDC. Based on the concentration of IgE, a complex relationship was found between surface bound IgE and expression of FcεRI on cDC. pDC exhibited a linear relationship of FcεRI expression and bound IgE that was consistent through all IgE concentrations.
In children, FcεRI expression on cDC and pDC is modulated differently by serum and cell bound IgE. IgE governance of FcεRI expression on cDC depends upon a complex relationship. Further studies are needed to determine the functional roles of FcεRI on cDC and pDC.
Rationale Decreased percentage of Th17 is seen in Hyperimmunoglobulin E Syndrome (HIES), although reports have suggested that TH17 levels are also low in atopic disease. Since eczema is often the ...first, and sometimes only presenting symptom of HIES, it is important to differentiate between the two entities.
Egr-1 (early growth response gene-1) is an immediate early gene encoding a zinc finger motif-containing transcription factor. Upon cross-linking of BCR, mature B cells undergo proliferation with an ...increase in Egr-1 message. Immature B lymphoma cells that express Egr-1 message and protein constitutively are growth inhibited when Egr-1 is down-regulated by negative signals from BCR or by antisense oligonucleotides. To test the hypothesis that Egr-1 is important for B cell development, we examined B cells from primary and secondary lymphoid organs in Egr-1(-/-) mice. Marginal zone B cell development was arrested in these mice, whereas the B cells in all other compartments were increased. To test the hypothesis that Egr-1 function may be partially compensated by other Egr family members, we developed transgenic mice expressing a dominant negative form of Egr-1, which lacks the trans activation domain but retains the DNA-binding domain, in a B cell-specific manner. There was a decrease in B lymphopoiesis in the bone marrow accompanied by a reduction in splenic immature and mature B cells as well as marginal zone B cells in the transgenic mice. Moreover, transgenic mice respond poorly to BCR cross-linking in vitro and T-independent and T-dependent Ags in vivo.
Abstract A subset of CD4+ T cells, the CD4+ CD25+ regulatory T (Treg ) cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo ...studies have indicated that T cell receptor (TCR) signal is required for development of such ‘natural regulatory (Treg ) cells’ and for activation of the effector function of CD4+ CD25+ regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes, the B-1 cells, primarily localized to coelomic cavities, Peyer's patches, tonsils and spleen. CD5 acts as a negative regulator of T cell and B cell signaling via recruitment of SHP-1. Here, we demonstrate that Treg cells obtained from CD5−/− mice are more potent than those from wild type mice in suppressing the in vitro cell proliferation of anti-CD3 stimulated CD4+ CD25− responder T cells. This phenomenon was cell contact and GITR dependent. Lack of CD5 expression on Treg cells (from spleen, lymph node and thymus) did not affect the intracellular levels of Foxp3. However, CD5−/− Treg thymocytes were able to elicit a higher Ca2+ response to TCR + co-stimulatory signals than the wild type cells. CD5−/− mice expressed more Foxp3 mRNA in the colon than wild type mice, and additionally, the severity of the dextran sulfate sodium (DSS)-induced colitis in CD5−/− mice was less than the wild type strain. We suggest that manipulation of CD5 expression or the downstream signaling components of CD4+ CD25+ Treg cells as a potential strategy for therapeutic intervention in cases of auto-immune disorders.
Abstract
Background
Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has principally been performed through the use of real-time reverse-transcription polymerase ...chain reaction testing. Results of such tests can be reported as cycle threshold (Ct) values, which may provide semi-quantitative or indirect measurements of viral load. Previous reports have examined temporal trends in Ct values over the course of a SARS-CoV-2 infection.
Methods
Using testing data collected during a prospective household transmission investigation of outpatient and mild coronavirus disease 2019 cases, we examined the relationships between Ct values of the viral RNA N1 target and demographic, clinical, and epidemiological characteristics collected through participant interviews and daily symptom diaries.
Results
We found that Ct values are lowest (corresponding to a higher viral RNA concentration) soon after symptom onset and are significantly correlated with the time elapsed since onset (P < .001); within 7 days after symptom onset, the median Ct value was 26.5, compared with a median Ct value of 35.0 occurring 21 days after onset. Ct values were significantly lower among participants under 18 years of age (P = .01) and those reporting upper respiratory symptoms at the time of sample collection (P = .001), and were higher among participants reporting no symptoms (P = .05).
Conclusions
These results emphasize the importance of early testing for SARS-CoV-2 among individuals with symptoms of respiratory illness, and allow cases to be identified and isolated when their viral shedding may be highest.
Abstract
Background
To better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described participant ...characteristics associated with the first negative rRT-PCR test (resolution), and determined if replication-competent viruses was recoverable ≥10 days after symptom onset.
Methods
We collected serial nasopharyngeal specimens from 109 individuals with rRT-PCR–confirmed COVID-19 in Utah and Wisconsin. We calculated viral RNA shedding resolution probability using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR–positive nasopharyngeal specimens collected ≥10 days after symptom onset.
Results
The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged <18 years (adjusted hazards ratio aHR, 3.01; 95% confidence interval CI, 1.6–5.6) and longer among those aged ≥50 years (aHR, 0.50; 95% CI, .3–.9) compared to participants aged 18–49 years. No replication-competent viruses were recovered.
Conclusions
Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.
The majority of participants with mild to moderate COVID-19 continued to shed SARS-CoV-2 from the nasopharynx ≥10 days after symptom onset. However, we did not recover any replication-competent virus from 35 rRT-PCR–positive nasopharyngeal specimens collected ≥10 days after symptom onset.
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