Cytokine storm syndrome (CSS) is a critical clinical condition induced by a cascade of cytokine activation, characterized by overwhelming systemic inflammation, hyperferritinaemia, haemodynamic ...instability and multiple organ failure (MOF). At the end of 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in Wuhan, China, and rapidly developed into a global pandemic. More and more evidence shows that there is a dramatic increase of inflammatory cytokines in patients with COVID‐19, suggesting the existence of cytokine storm in some critical illness patients. Here, we summarize the pathogenesis, clinical manifestation of CSS, and highlight the current understanding about the recognition and potential therapeutic options of CSS in COVID‐19.
Introduction
During an out-of-hours shift, the initial assessment of a CAMHS patient is performed by the paediatric trainee, usually the paediatric SHO (senior-house-officer). During my placement as ...a paediatric SHO, I was aware of a gap in formalised metal state examination teaching for paediatric juniors, which would be crucial for a thorough assessment of these patients, and to better guarantee they are safely managed until further assessment.
Objectives
The aim is to provide a short teaching session on mental state examining of the CAMHS patent to paediatric SHOs in order to improve their confidence in assessment.
Methods
In order to assess initial confidence in assessing the mental-state of a CAMHS patient, a pre-teaching questionnaire was given to the paediatric SHOs. A 30-minute teaching session on the mental state exam was then carried out and a post-teaching questionnaire was then given to the same trainees.
Results
Paired sample Wilcoxons signed rank test found that training significant improved trainees’ confidence in taking a psychiatric mental state exam (p= 0.005, r = 0.628), and improved their confidence in presenting a mental state exam (p = 0.0041, r = 0.6420).
Conclusions
Being able to confidently assess the mental state of a CAMHS patient in an on call shift is important for the initial assessing paediatric trainee. However this is often not taught in the paediatric curriculum and trainees have expressed some anxiety in performing this assessment overnight, before a more comprehensive assessment by a CAMHS professional. A simple teaching session may help to reduce this anxiety and improve trainees’ confidence.
The diagnosis of postacute sequelae of coronavirus disease 2019 (PASC) poses an ongoing medical challenge. To identify biomarkers associated with PASC we analyzed plasma samples collected from PASC ...and coronavirus disease 2019 patients to quantify viral antigens and inflammatory markers. We detect severe acute respiratory syndrome coronavirus 2 spike predominantly in PASC patients up to 12 months after diagnosis.
A reproducible stationary high-confinement regime with small "edge-localized modes" (ELMs) has been achieved recently in the Experimental Advanced Superconducting Tokamak, which has a metal wall and ...low plasma rotation as projected for a fusion reactor. We have uncovered that this small ELM regime is enabled by a wide edge transport barrier (pedestal) with a low density gradient and a high density ratio between the pedestal foot and top. Nonlinear simulations reveal, for the first time, that the underlying mechanism for the observed small ELM crashes is the upper movement of the peeling boundary induced by an initial radially localized collapse in the pedestal, which stops the growth of instabilities and further collapse of the pedestal, thus providing a physics basis for mitigating ELMs in future steady-state fusion reactors.
With more than 38 million people living with HIV-1 (PLWH) worldwide, developing a cure for HIV-1 remains a major global health priority. Lifelong persistence of HIV-1 is frequently attributed to a ...pool of stable, transcriptionally silent HIV-1 proviruses, which are unaffected by currently available antiretroviral therapy (ART) or host immune activity. In this opinion article, we propose a more dynamic interpretation of HIV-1 reservoir cell biology and argue that HIV-1 proviruses frequently display residual viral transcriptional activity, making them vulnerable to longitudinal immune-mediated selection processes. Such mechanisms may, over extended periods of ART, induce an attenuated viral reservoir profile characterized by intact proviruses preferentially integrated into heterochromatin locations. We suggest that intensifying and accelerating naturally occurring selection mechanisms might represent a promising strategy for finding a potential cure for HIV-1 infection.
Dendritic cells (DCs) are professional antigen-presenting cells that link innate and adaptive immunity and are critical for the induction of protective immune responses against pathogens. Proportions ...of these cells are markedly decreased in the blood of untreated HIV-1-infected individuals, suggesting they might be intrinsically involved in HIV-1 pathogenesis. However, despite several decades of active research, the precise role and contribution of these cells to protective or detrimental host responses against HIV-1 are still remarkably unclear. Recent studies have shown that DCs possess a fine-tuned machinery to recognize HIV-1 replication products through a variety of innate pathogen sensing mechanisms, which may be instrumental for generating both cellular and humoral protective immune responses in persons who naturally control HIV-1 replication. Yet, dysregulated and abnormal activation of DCs might also contribute to sustained inflammation and immune activation accelerating disease progression during chronic progressive infection. Emerging data also suggest that DCs can influence the induction of potent broadly-neutralizing antibodies, and may, for this reason, have to be considered as important components of future HIV-1 vaccination strategies. Apart from their involvement in antiviral host immunity, at least a subgroup of DCs seem intrinsically susceptible to HIV-1 infection and may serve as a viral target cell population. Indeed recent studies suggest that specific DC subpopulations residing in the genital mucosa are preferentially infected by HIV-1 and play an active role in sexual transmission; therefore, DCs may contribute to viral dissemination and possible persistence of the viral reservoirs through either direct or indirect mechanisms. Here, we analyze the distinct and partially opposing roles of DCs during HIV-1 disease pathogenesis, with a focus on implications of DC biology natural immune control and HIV cure research efforts.
This letter describes an immunocompromised patient who had persistent infection with SARS-CoV-2 over a period of months, despite several courses of remdesivir. Phylogenetic analysis showed ...accelerated viral evolution.
Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant economic and health damage worldwide. Rapid ...vaccination is one of the key strategies to curb severe illness and death due to SARS-CoV-2 infection. Hundreds of millions of people worldwide have received various COVID-19 vaccines, including mRNA vaccines, inactivated vaccines and adenovirus-vectored vaccines, but the side effects and efficacy of most vaccines have not been extensively studied. Recently, there have been increasing reports of immunoglobulin A nephropathy (IgAN) after COVID-19 vaccination, however, whether their relationship is causal or coincidental remains to be verified. Here, we summarize the latest clinical evidence of IgAN diagnosed by renal biopsy associated with the COVID-19 vaccine published by 10 July 2022 with the largest sample size, and propose a hypothesis for the pathogenesis between them. At the same time, the new opportunity presented by COVID-19 vaccine allows us to explore the mechanism of IgAN recurrence for the first time. Indeed, we recognize that large-scale COVID-19 vaccination has enormous benefits in preventing COVID-19 morbidity and mortality. The purpose of this review is to help guide the clinical assessment and management of IgA nephropathy post-COVID-19 vaccination and to enrich the 'multi-hit' theory of IgA nephropathy.
As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is ...critical.
Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified.
A total of 192 children (mean age, 10.2 ± 7.0 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met the criteria for MIS-C. Only 25 children (51%) with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were nonspecific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower angiotensin-converting enzyme 2 expression (P = .004). Immunoglobulin M (IgM) and Immunoglobulin G (IgG) to the receptor binding domain of the SARS-CoV-2 spike protein were increased in severe MIS-C (P < .001), with dysregulated humoral responses observed.
This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic despite having milder disease or a lack of symptoms; immune dysregulation is implicated in severe postinfectious MIS-C.
HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered “transcriptionally silent,” but active viral gene expression may occur in some cells, challenging the ...concept of viral latency. Applying an assay for profiling the transcriptional activity and the chromosomal locations of individual proviruses, we describe a global genomic and epigenetic map of transcriptionally active and silent proviral species and evaluate their longitudinal evolution in persons receiving suppressive ART. Using genome-wide epigenetic reference data, we show that proviral transcriptional activity is associated with activating epigenetic chromatin features in linear proximity of integration sites and in their inter- and intrachromosomal contact regions. Transcriptionally active proviruses were actively selected against during prolonged ART; however, this pattern was violated by large clones of virally infected cells that may outcompete negative selection forces through elevated intrinsic proliferative activity. Our results suggest that transcriptionally active proviruses are dynamically evolving under selection pressure by host factors.
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•A multidimensional assay for HIV-1 reservoir cell profiling is presented (PRIP-seq)•Transcriptionally active HIV-1 proviruses are actively selected against during ART•Large transcriptionally active proviral clones resist negative host selection forces•Epigenetic signals in linear and 3D chromatin contacts influence HIV-1 transcription
PRIP-seq is a multidimensional single-cell assay that simultaneously captures the proviral sequence, the corresponding chromosomal integration site, and the expression of HIV-1 RNA in single virally infected cells and allows for the global mapping of transcriptionally active and silent proviruses in patients receiving suppressive antiretroviral therapy.
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