Macroevolution of virulence shifts in human-infective RNA virus species

Study Objectives: To determine the frequency and distribution of virulence shifts across 40 viral genera that include human-infective RNA virus species using evolutionary discrete trait models. Methods: An inhouse database containing RNA-dependent RNA polymerase (RdRp) gene sequences from human and non-human infective RNA virus species was updated in January – March 2021. RdRp gene sequences were obtained from NCBI GenBank for newly identified virus species. Data describing viral virulence in humans was obtained by a literature search in June 2021 and virus species were categorized as either being non-human-infective, non-severe, moderate or severe. Phylogenetic trees based on the RdRp gene sequences were estimated, discrete virulence trait evolution modelled, and discrete virulence trait transitions counted. Results: The final dataset contained RdRp gene sequences of 579 viral species. 38.3% (222) of all viruses were human-infective of which 21.6% (48) were classified as severe, 11.7% (26) as moderate and 66.7% (148) as non-severe. The Flavivirus genus had the highest number of severe virus species (10). 83% of severe virus species or clades were likely to have evolved from non-human-infective ancestral viruses. Large virulence increases once a virus had evolved the ability to infect humans were rare as only 2 transitions from non-severe to severe were observed. Discrete trait transitions from severe to non-severe were more frequent with 10 transitions. Transition to moderate from non-severe or severe were more balanced with evidence of 8 and 4 transitions, respectively. When transitions from no-human- infective viruses to any virulence class were stratified by envelope, genome and transmission mode, no transitions to severe were found for non-enveloped, dsRNA and vector-borne viruses. Conclusion: This study fits within a broader framework of comparative studies that attempts to understand the variation in virulence of viral genera that contain human- infective RNA viruses. The findings from this study suggest that, from a macroevolutionary viewpoint, the evolution of large virulence transitions are infrequent once RNA virus species have evolved human-infectivity

Unusually Divergent Ubiquitin Genes and Proteins in Plasmodium Species

Ubiquitin is an extraordinarily highly conserved 76 amino acid protein encoded by three different types of gene, where the primary translation products are fusions either of ubiquitin with one of two ribosomal proteins (RPs) or of multiple ubiquitin monomers from head to tail. Here, we investigate the evolution of ubiquitin genes in mammalian malaria parasites (Plasmodium species). The ubiquitin encoded by the RPS27a fusion gene is highly divergent, as previously found in a variety of protists. However, we also find that two other forms of divergent ubiquitin sequence, each previously thought to be extremely rare, have arisen recently during the divergence of Plasmodium subgenera. On two occasions, in two distinct lineages, the ubiquitin encoded by the RPL40 fusion gene has rapidly diverged. In addition, in one of these lineages, the polyubiquitin genes have undergone a single codon insertion, previously considered a unique feature of Rhizaria. There has been disagreement whether the multiple ubiquitin coding repeats within a genome exhibit concerted evolution or undergo a birth-and-death process; the Plasmodium ubiquitin genes show clear signs of concerted evolution, including the spread of this codon insertion to multiple repeats within the polyubiquitin gene.</p

Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection.

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [18F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations

A Rapid Evidence Appraisal of influenza vaccination in health workers: an important policy in an area of imperfect evidence

IntroductionThe World Health Organization recommends vaccination of health workers (HWs) against influenza, but low uptake is intransigent.We conducted a Rapid Evidence Appraisal on: the risk of influenza in HWs, transmission risk from HWs to patients, the benefit of HW vaccination, and strategies for improving uptake. We aimed to capture a ‘whole-of-system’ perspective to consider possible benefits for HWs, employers and patients.MethodsWe executed a comprehensive search of the available literature published from 2006 to 2018 in the English language. We developed search terms for seven separate questions following the PICO framework (population, intervention, comparators, outcomes) and queried nine databases.ResultsOf 3784 publications identified, 52 met inclusion criteria. Seven addressed HW influenza risk, of which four found increased risk; 15 addressed influenza vaccine benefit to HWs or their employers, of which 10 found benefit; 11 addressed influenza transmission from HWs to patients, of which 6 found evidence for transmission; 12 unique studies addressed whether vaccinating HWs produced patient benefit, of which 9 concluded benefits accrued. Regarding the number of HWs needed to vaccinate (NNV) to deliver patient benefit, NNV estimates ranged from 3 to 36,000 but were in significant disagreement. Fourteen studies provided insights on strategies to improve uptake; the strongest evidence was for mandatory vaccination.ConclusionsThe evidence on most questions related to influenza vaccination in HWs is mixed and often of low-quality. Substantial heterogeneity exists in terms of study designs and settings, making comparison between studies difficult. Notwithstanding these limitations, a majority of studies suggests that influenza vaccination benefit HWs and their employers; and HWs are implicated in transmission events. The effects of vaccinating HWs on patient morbidity and mortality may include reductions in all-cause mortality and influenza-like illness (ILI). Taken together, the evidence suggests that HW vaccination is an important policy for HWs themselves, their employers, and their patients

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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