48 research outputs found

    A paradigm shift in the diagnosis of aspiration pneumonia in older adults

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    In older adults, community-acquired pneumonia (CAP) is often aspiration-related. However, as aspiration pneumonia (AP) lacks clear diagnostic criteria, the reported prevalence and clinical management vary greatly. We investigated what clinical factors appeared to influence the diagnosis of AP and non-AP in a clinical setting and reconsidered a more clinically relevant approach. Medical records of patients aged ≥75 years admitted with CAP were reviewed retrospectively. A total of 803 patients (134 APs and 669 non-APs) were included. The AP group had significantly higher rates of frailty, had higher SARC-F scores, resided in institutions, had neurologic conditions, previous pneumonia diagnoses, known dysphagia, and were more likely to present with vomiting or coughing on food. Nil by mouth orders, speech therapist referrals, and broad-spectrum antibiotics were significantly more common, while computed tomography scans and blood cultures were rarely performed; alternative diagnoses, such as cancer and pulmonary embolism, were detected significantly less. AP is diagnosed more commonly in frail patients, while aspiration is the underlying aetiology in most types of pneumonia. A presumptive diagnosis of AP may deny patients necessary investigation and management. We suggest a paradigm shift in the way we approach older patients with CAP; rather than trying to differentiate AP and non-AP, it would be more clinically relevant to recognise all pneumonia as just pneumonia, and assess their swallowing functions, causative organisms, and investigate alternative diagnoses or underlying causes of dysphagia. This will enable appropriate clinical management

    Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

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    SARS-CoV-2オミクロンBA.2.75株(通称ケンタウロス)のウイルス学的性状の解明. 京都大学プレスリリース. 2022-10-12.The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5

    Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

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    In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions

    Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

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    In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022
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