Search

Summary ParagraphTwo years into the SARS-CoV-2 pandemic, the post-acute sequelae of infection are compounding the global health crisis. Often debilitating, these sequelae are clinically heterogeneous and of unknown molecular etiology. Here, a transcriptome-wide investigation of this new condition was performed in a large cohort of acutely infected patients followed clinically into the post-acute period. Gene expression signatures of post-acute sequelae were already present in whole blood during the acute phase of infection, with both innate and adaptive immune cells involved. Plasma cells stood out as driving at least two distinct clusters of sequelae, one largely dependent on circulating antibodies against the SARS-CoV-2 spike protein and the other antibody-independent. Altogether, multiple etiologies of post-acute sequelae were found concomitant with SARS-CoV-2 infection, directly linking the emergence of these sequelae with the host response to the virus.

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C., Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Transcriptional quiescence, an evolutionarily conserved trait, distinguishes the embryonic primordial germ cells (PGCs) from their somatic neighbors. InDrosophila melanogaster, PGCs from embryos maternally compromised forgerm cell-less(gcl) misexpress somatic genes, possibly resulting in PGC loss. Recent studies documented a requirement for Gcl during proteolytic degradation of the terminal patterning determinant, Torso receptor. Here we demonstrate that the somatic determinant of female fate,Sex-lethal(Sxl), is a biologically relevant transcriptional target of Gcl. Underscoring the significance of transcriptional silencing mediated by Gcl, ectopic expression of a degradation-resistant form of Torso (torsoDeg) can activateSxltranscription in PGCs, whereas simultaneous loss oftorso-like(tsl) reinstates the quiescent status ofgclPGCs. Intriguingly, likegclmutants, embryos derived from mothers expressingtorsoDegin the germline display aberrant spreading of pole plasm RNAs, suggesting that mutual antagonism between Gcl and Torso ensures the controlled release of germ-plasm underlying the germline/soma distinction.

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C., Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Communication during a public health emergency event is a complex process. The objective of the present systematic review was to examine the extant literature related to such events to answer the following question: What are the best ways to communicate uncertainties to public audiences, at-risk communities, and stakeholders? The search for literature was in multiple languages; it had a focus on English and included Arabic, Chinese, French, Russian, and Spanish. The search included published studies, grey literature, and media reports. The found literature was narrowed to select only data-based primary studies, which were classified into four methodological streams: Quantitative-comparison groups; Quantitative-descriptive survey; Qualitative; and Mixed-method and case study. Study characteristics extracted from individual studies of all methodological streams included study method, country focus, disaster/ emergency type, disaster/ emergency phase, and at-risk/ vulnerable population. Study findings for all methodological streams were extracted as narrative findings. The synthesis of findings was done in two stages. In the first stage, findings from individual studies were synthesized within methodological streams and then these within-method synthesized findings were evaluated for certainty/ confidence using appropriate tools. In the second stage, the within-method synthesized findings were synthesized across methodological streams to develop an overarching synthesis of findings. In both the within-method and across-method stages, the synthesis of findings included subgroup analyses related to type of emergency event, phase of emergency event, country of emergency event, and presence of vulnerable population. The last two subgroups allowed considerations of equity in the synthesized findings. For English language literature search, almost 2900 titles and abstracts were scanned, of which about 1700 full-texts were quickly read. After this, 73 full-texts were downloaded, of which 33 data-based primary studies were selected for data extraction. For Arabic, Chinese, French, Russian, and Spanish languages all together almost 8600 titles and abstracts were scanned, of which about 900 full-texts were downloaded, of which 16 were fully read and then 13 data-based primary studies were selected for data extraction. The results showed that country coverage was of mostly high and middle-income countries in Asia, Europe, North America, and Oceania. The event most covered was infectious disease; other relatively common events included flood and earthquake. The final set of across-method synthesized findings showed that uncertainty in public health emergency events is a multi-faceted concept with multiple components. There is general agreement among experts and researchers, though with some exceptions, that communication by authorities to the public should include explicit information about uncertainties associated with events. However, it is important to ensure that the information provided is consistent and not contradictory, and is presented clearly and in an easy to understand manner. The findings also showed that uncertainty related to public health emergency events requires a distinction between uncertainty experience and uncertainty information. It is likely that uncertainty is experienced and uncertainty information is understood and misunderstood in the same general ways by both the public and experts. The experience of uncertainty may be a defining feature of a public health emergency event not only for the public and experts, but for the media as well as it has to often deal with contradictory and inconsistent uncertain information.