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Membranoproliferative glomerulonephritis (MPGN) comprises a histologic pattern of glomerular injury with different underlying diseases. Here we report on a 47-year-old female with rapidly progressive glomerulonephritis (RPGN) on top of a previously diagnosed idiopathic MPGN after receiving the first dose of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) mRNA vaccine. After aggressive immunosuppression her serum creatinine returned to normal values, along with reduction of proteinuria. Recently, numerous publications have reported an association of glomerular diseases with COVID-19 vaccination. Our case presents to the best of our knowledge the first occurrence of possible association of COVID-19 mRNA vaccination with a crescentic form of MPGN.

The process of finding molecules that bind to a target protein is a challenging first step in drug discovery. Crystallographic fragment screening is a strategy based on elucidating binding modes of small polar compounds and then building potency by expanding or merging them. Recent advances in high-throughput crystallography enable screening of large fragment libraries, reading out dense ensembles of fragments spanning the binding site. However, fragments typically have low affinity thus the road to potency is often long and fraught with false starts. Here, we take advantage of high-throughput crystallography to reframe fragment-based hit discovery as a denoising problem – identifying significant pharmacophore distributions from a fragment ensemble amid noise due to weak binders – and employ an unsupervised machine learning method to tackle this problem. Our method screens potential molecules by evaluating whether they recapitulate those fragment-derived pharmacophore distributions. We retrospectively validated our approach on an open science campaign against SARS-CoV-2 main protease (Mpro), showing that our method can distinguish active compounds from inactive ones using only structural data of fragment-protein complexes, without any activity data. Further, we prospectively found novel hits for Mpro and the Mac1 domain of SARS-CoV-2 non-structural protein 3. More broadly, our results demonstrate how unsupervised machine learning helps interpret high throughput crystallography data to rapidly discover of potent chemical modulators of protein function.

SUMMARY The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localises to mitochondria during infection, where it inhibits innate immunity by restricting IFN-β production, but not NF-κB activation or JAK-STAT signalling downstream of type I IFN stimulation. We find that ORF3c acts after stimulation with cytoplasmic RNA helicases RIG-I or MDA5 or adaptor protein MAVS, but not after TRIF, TBK1 or phospho-IRF3 stimulation. ORF3c co-immunoprecipitates with the antiviral proteins MAVS and PGAM5 and induces MAVS cleavage by caspase-3. Together, these data provide insight into an uncharacterised mechanism of innate immune evasion by this important human pathogen.

Peer reviewed: True Here researchers have the disposition to engage in the scholarly discourse on how the pandemic adversely influenced individuals' mental health and what remedies should be exercised in response to the mental health challenges. There is a shortage of scholarly discussion about who benefitted from the occurrence of the pandemic. Mancini et al. argued that the pandemic benefitted the social and mental health functioning of a subset of the population, despite the pandemic causing considerable risks of harm to mental health. In this perspective, the author summarizes relevant findings and arguments to present which subsets of the population benefitted at school, at home, and in the workplace during the pandemic. Although COVID-19 is no longer deemed a pandemic, many by-products of the public health crisis, including the encouragement of remote work and studies, remain. In this perspective, by understanding who benefitted from the pandemic and why, the author can evaluate if any public policies formed in response to the pandemic should be kept in the long run in order to maximize individuals' mental health.

Background Adherence to pharmacological interventions in clinical trials is crucial for correct estimation of beneficial and adverse effects, including trials of SARS-CoV-2. The Template for Intervention Description and Replication (TIDieR) – a 12-item extension of the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines – includes two items (11 and 12) that address intervention adherence reporting in trial publications. Objective To assess compliance with TIDieR items 11 and 12 of randomised controlled trials (RCTs) of interventions in SARS-CoV-2 infection published in five selected journals during 2021. Methods We assessed SARS-CoV-2 pharmacological RCTs published in the Annals of Internal Medicine, The BMJ, JAMA, The Lancet , and The New England Journal of Medicine in 2021 for compliance with TIDieR items 11 and 12. Item 11 was assessed in two parts: 11a—how intervention adherence was assessed; 11b—if any strategies were used to maintain or improve how intervention adherence was maintained or improved. Item 12 assessed the extent to which the intervention was delivered as planned. We calculated raw adherence and proportional (weighted) adherence for pharmacological and comparator interventions where available. Results We found 75 eligible RCTs, of which 28 (37%) reported results related to SARS-CoV-2 vaccinations. Compliance with items 11a and 12 could be assessed in 71 of these 75. Of those 71 RCTs, 37 (52%, 95% confidence interval 40–64%) were compliant with reporting of item 11a. Seven RCTs had a strategy to assess compliance with item 11b, and only three (43%, 9–82%) of those complied with item 11b reporting. Of the 71 RCTs, 70 complied with reporting of item 12. Only one of the 71 RCTs (1.4%, 0–7.6%) fully complied with TIDieR items 11a, 11b, and 12. Compliance varied across journals. Conclusions RCTs of SARS-CoV-2 pharmacological interventions published in high-impact medical journals complied variably with reporting of intervention adherence, even though the journals endorse CONSORT. The implications for interpretation, application, and replication of findings based on these publications warrant consideration.

Funder: UK Research and Innovation; Id: http://dx.doi.org/10.13039/100014013 Funder: Academic Clinical Lecturer Funder: Applied Research Collaboration East Midlands (ARC EM)

The primary objective of this scoping review is to understand the extent and type of evidence in relation to moral injury in social work staff. The secondary objective is to establish how moral injury has been defined in the literature in the context of social work. The review question is: what is currently known about moral injury in social work staff?

ABSTRACT Intensive care unit (ICU) staff continue to face recurrent work-related traumatic events throughout the COVID-19 pandemic. Intrusive memories (IMs) of such traumatic events comprise sensory image-based memories. Harnessing research on preventing IMs with a novel behavioural intervention on the day of trauma, here we take critical next steps in developing this approach as a treatment for ICU staff who are already experiencing IMs days, weeks, or months post-trauma. To address the urgent need to develop novel mental health interventions, we used Bayesian statistical approaches to optimise a brief imagery-competing task intervention to reduce the number of IMs. We evaluated a digitised version of the intervention for remote, scalable delivery. We conducted a two-arm, parallel-group, randomised, adaptive Bayesian optimisation trial. Eligible participants worked clinically in a UK NHS ICU during the pandemic, experienced at least one work-related traumatic event, and at least three IMs in the week prior to recruitment. Participants were randomised to receive immediate or delayed (after four weeks) access to the intervention. Primary outcome was the number of IMs of trauma during week 4, controlling for baseline week. Analyses were conducted on an intention-to-treat basis as a between-group comparison. Prior to final analysis, sequential Bayesian analyses were conducted ( n =20,23,29,37,41,45) to inform early stopping of the trial prior to the planned maximum recruitment ( n =150). Final analysis ( n =75) showed strong evidence for a positive treatment effect (Bayes factor, BF=1.25 × 10 6 ): the immediate arm reported fewer IMs (median=1, IQR=0-3) than the delayed arm (median=10, IQR=6-16.5). With further digital enhancements, the intervention ( n =28) also showed a positive treatment effect (BF=7.31). Sequential Bayesian analyses provided evidence for reducing IMs of work-related trauma for healthcare workers. This methodology also allowed us to rule out negative effects early, reduced the planned maximum sample size, and allowed evaluation of enhancements. Trial Registration NCT04992390 ( www.clinicaltrials.gov ).