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[...]as of the beginning of April, 2024, the estimated variant frequency of KP.2 has already reached 20% in the UK (appendix p 15). Altogether, these results suggest that the increased immune escape ability of KP.2 contributes to its higher Re compared with JN.1. YKa, KU, YKo, and KO contributed equally to this study.

Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases 1 – 3 . Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium . These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis. The microbiota of centenarians (aged 100 years and older) comprise gut microorganisms that are capable of generating unique secondary bile acids, including isoallolithocholic acid, a bile acid with potent antimicrobial effects against Gram-positive—but not Gram-negative—multidrug-resistant pathogens.

Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions 1 – 3 . However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium . Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells 4 , 5 . Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection. Colonization of trypsin-degrading commensal bacteria may contribute to the maintenance of intestinal homeostasis and protection against pathogen infection in humans and mice.

Purpose The BioFire FilmArray® Meningitis/Encephalitis Panel (FAMEP) is designed to rapidly and accurately detect common multiple pathogens that cause central nervous system (CNS) infection, including viruses, bacteria, and yeast. The FAMEP’s usefulness in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) has not been fully evaluated. This retrospective study evaluated the usefulness of the FAMEP in the screening for CNS infection after allogeneic HSCT. Methods Cerebrospinal fluid (CSF) was obtained from 12 patients to evaluate the causes of CNS disorders after allogeneic HSCT, and the FAMEP was applied. Results The median day of the FAMEP evaluations was 27 days post-transplant (range, 0–390). Human herpesvirus 6 (HHV-6) was detected in three patients and cytomegalovirus was detected in one patient, leading to the diagnosis of encephalitis/myelitis. In three patients (HHV-6, n  = 2; CMV, n  = 1), the presence of the viruses was confirmed by conventional real-time polymerase chain reaction (PCR). However, in the remaining patient with HHV-6 detected by the AMEP, HHV-6 was not detected by real-time PCR at the onset but was detected 7 days later. The treatments for the detected viruses improved the clinical conditions in the four patients. Conclusions Our results suggest that the FAMEP can be a useful sensitive assay in the screening and diagnosis of CNS viral infections after allogeneic HSCT.

[...]we have found that natural infection with XBB subvariants, including XBB.1.5, does not efficiently induce humoral immunity against the infecting XBB subvariants.1–3 These observations raise the possibility that the XBB.1.5 monovalent vaccine might not be able to efficiently induce humoral immunity against emerging SARS-CoV-2 variants, including a variety of XBB subvariants (XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and HK.3) as well as BA.2.86. Importantly, in the case of the XBB.1.5 vaccine sera without previous infection, XBB.1.5 vaccine also efficiently induced antiviral activity (2·1-fold to 3·9-fold) against all variants tested with statistical significance (figure A). The induction efficiency of neutralising activity was comparable between the infection-naive cohort (figure A) and the XBB-infected cohort (figure B). [...]although all prevaccination sera from the XBB-infected cohort showed antiviral activity against all variants tested, some individuals vaccinated with XBB.1.5 vaccine without natural infection showed no antiviral activity against XBB.1.5 (n=2), XBB.1.16 (n=1), XBB.2.3 (n=3), EG.5.1 (n=3), HK.3 (n=3), and BA.2.86 (n=2).

The antibody titer is known to wane within months after receiving two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine. However, knowledge of the cellular immune response dynamics following vaccination is limited. This study to aimed to determine antibody and cellular immune responses following vaccination, and the incidence and determinants of breakthrough infection. This prospective cohort study a 6-month follow-up period was conducted among Japanese healthcare workers. All participants received two doses of BNT162b2 vaccine. Anti-SARS-CoV-2 antibody titers and T-cell immune responses were measured in serum samples collected at several timepoints before and after vaccination. A total of 608 participants were included in the analysis. Antibody titers were elevated 3 weeks after vaccination and waned over the remainder of the study period. T-cell immune responses showed similar dynamics. Six participants without predisposing medical conditions seroconverted from negative to positive on the IgG assay for nucleocapsid proteins, indicating breakthrough SARS-CoV-2 infection. Five of the six breakthrough infections were asymptomatic. Both humoral and cellular immunity waned within 6 months after BNT162b2 vaccination. The incidence of asymptomatic breakthrough infection within 6 months after vaccination was approximately one percent. UMIN000043340.

Effective early-stage markers for predicting which patients are at risk of developing SARS-CoV-2 infection have not been fully investigated. Here, we performed comprehensive serum metabolome analysis of a total of 83 patients from two cohorts to determine that the acceleration of amino acid catabolism within 5 days from disease onset correlated with future disease severity. Increased levels of de-aminated amino acid catabolites involved in the de novo nucleotide synthesis pathway were identified as early prognostic markers that correlated with the initial viral load. We further employed mice models of SARS-CoV2-MA10 and influenza infection to demonstrate that such de-amination of amino acids and de novo synthesis of nucleotides were associated with the abnormal proliferation of airway and vascular tissue cells in the lungs during the early stages of infection. Consequently, it can be concluded that lung parenchymal tissue remodeling in the early stages of respiratory viral infections induces systemic metabolic remodeling and that the associated key amino acid catabolites are valid predictors for excessive inflammatory response in later disease stages. Here the authors show that elevated serum levels of deaminated amino acid catabolites involved in de novo nucleotide synthesis pathway correlate with later COVID-19 severity. These elevated levels are likely associated with abnormal proliferation of airway and vascular cells in the lung.

•Neutralization antibody were measured against SARS-CoV-2 variants after vaccination.•Low neutralization antibody titer was observed against beta and delta variants.•Neutralization antibody titer against R.1 lineage was equivalent to original Wuhan.•The weakened humoral response might not be caused solely by the E484K mutation. The reduced vaccine efficacy against the SARS-CoV-2 variant lineage B. 1.351 (beta variant) containing the E484K and N501Y mutations is well known. The E484K mutation in SARS-CoV-2 is thought to be responsible for weakened humoral immunity. Vaccine efficacy against the R.1 lineage, which contains the E484K mutation but not the N501Y mutation, is uncertain. Serum samples were collected from 100 healthy Japanese participants three weeks after receiving the second dose of the BNT162b2 vaccine, and serum neutralization antibody titers were measured against five SARS-CoV-2 variants. The geometric mean neutralization titers measured for the original and R.1 lineages were equivalent (91.90 ± 2.40 and 102.67 ± 2.28, respectively), whereas a low titer was measured for the beta variant (18.03 ± 1.92). Although further investigations with other variant strains and serum samples are essential, our results imply that the weakened humoral response is not caused solely by the E484K mutation. (UMIN000043340).

Furthermore, salivary ribonuclease is speculated to affect the analysis of stored samples.3 From 15 May to 16 July 2020, we obtained nasopharyngeal swabs and saliva samples simultaneously, from patients admitted to Keio University Hospital (Tokyo, Japan) for COVID-19 treatment and from the university staff presenting symptoms suggesting acute viral infections, including fever, upper or lower respiratory symptoms, or diarrhoea. Viral culture results imply RNA fragmentation by ribonuclease could result in loss of viability but preserve the detectability by probe without decomposition for days. [...]Ct values of salivated samples were not fluctuated over time ex vivo, while initial Ct values were increased over time reflecting decreasing viral burden in vivo. [...]test results of SARS-CoV-2 RT-PCR using saliva collected in an acute phase were as accurate as those using nasopharyngeal swab samples, and saliva sample storage at a room temperature did not affect the test results. Funding This study was funded by Keio University Hospital and partly supported by a Research Program on Emerging and Re-emerging Infectious Diseases (JP19fk0108113) from the Japan Agency for Medical Research and Development and by the National Institutes of Allergy and Infectious Diseases-funded Center for Research on Influenza Pathogenesis (Grant HHSN272201400008C).

Understanding the factors that influence people’s decisions regarding vaccination is essential to promote vaccination. We aimed to clarify the motivations for receiving booster vaccines. We conducted a paper-based questionnaire distributed during January–February 2022 involving students and faculty staff who received the first COVID-19 vaccination at the mass vaccination program during June–September 2021 at Keio University. A total of 1725 participants were enrolled, and all completed the survey. Among these, 64.9% reported a significant adverse event (AEs) affecting daily life after the second vaccine. “Fear of severe COVID-19 illness” (72.6%) was the most common reason for getting vaccinated, followed by “concern of infecting others” (68.4%) and “fear of COVID-19 infection itself” (68.3%). Television emerged as the most influential source of information (80%), followed by university information (50.2%) and social networking sites (42.8%). Multivariate analysis revealed “fear of severe COVID-19 illness”, “fear of COVID-19 infection itself”, and “trust in the efficacy and safety of the vaccines in general” were significantly correlated with willingness to receive paid vaccinations. The severity of AEs and source of information were not related to participants’ willingness to receive booster vaccinations. Participants with positive reasons for vaccination were more likely to accept a third dose.