Recurrence is a rare complication of Group B Streptococcus (GBS) neonatal infections. We conducted a retrospective observational study on GBS neonatal invasive infections in France from 2007 to 2021. 1,527 cases were reported, of which 36 (2.36%) were recurrent. Recurrence mainly concerned preterm (68%) and low birthweight (72%) infants and was associated with the hypervirulent GBS clonal complex 17 (83%, OR 2.86, 95% CI 1.18-6.92). No beta-lactam tolerant strains were identified and bacterial whole genome sequencing could not reveal any specific feature associated with recurrence. Large cohort studies should be undertaken to address the optimal management of these uncommon diseases.

By acting as an environmental sensor, the ligand-induced transcription factor aryl hydrocarbon receptor (AhR) regulates acute innate and adaptive immune responses against pathogens. Here, we analyzed the function of AhR in a model for chronic systemic infection with attenuated Salmonella Typhimurium (STM). WT and AhR-deficient mice were infected with the attenuated STM strain TAS2010 and analyzed for bacterial burden, host defense functions and inflammatory stress erythropoiesis. AhR-deficient mice were highly susceptible to TAS2010 infection compared with WT mice demonstrated by reduced bacterial clearance and increased mortality. STM infection resulted in macrocytic anemia and enhanced splenomegaly along with destruction of the splenic architecture in AhR-deficient mice. In addition, AhR-deficient mice displayed a major expansion of splenic immature red blood cells, indicative of infection-induced stress erythropoiesis. Elevated serum levels of erythropoietin and interleukin-6 upon infection as well as increased numbers of splenic stress erythroid progenitors already in steady state probably drive this effect and might cause the alterations in splenic immune cell compartments, thereby preventing an effective host defense against STM in AhR-deficient mice. AhR-deficient mice fail to clear chronic TAS2010 infection due to enhanced stress erythropoiesis in the spleen and accompanying destruction of the splenic architecture.

Nipah virus is an emerging zoonotic virus that causes severe respiratory disease and meningoencephalitis. The pathophysiology of Nipah virus meningoencephalitis is poorly understood. We have collected the brains of African green monkeys during multiple Nipah virus, Bangladesh studies, resulting in 14 brains with Nipah virus-associated lesions. The lesions seen in the brain of African green monkeys infected with Nipah virus, Bangladesh were very similar to those observed in humans with Nipah virus, Malaysia infection. We observed viral RNA and antigen within neurons and endothelial cells, within encephalitis foci and in uninflamed portions of the CNS. CD8+ T cells had a consistently high prevalence in CNS lesions. We developed a UNet model for quantifying and visualizing inflammation in the brain in a high-throughput and unbiased manner. While CD8+ T cells had a consistently high prevalence in CNS lesions, the model revealed that CD68+ cells were numerically the immune cell with the highest prevalence in the CNS of NiV-infected animals. Our study provides an in-depth analysis on Nipah virus infection in the brains of primates, and similarities between lesions in patients and the animals in our study validate this model.

Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

Pregnant people with COVID-19 experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. IMPAACT 2032 was a phase IV prospective, open-label, non-randomized opportunistic study of hospitalized pregnant and non-pregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks post-last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and non-pregnant women were calculated. Fifty-three participants initiated remdesivir (25 pregnant; median (IQR) gestational age 27.6 (24.9, 31.0) weeks). Plasma exposures of remdesivir, its two major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and non-pregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI 1.35, 3.03) with each additional infusion in non-pregnant versus pregnant participants. Three adverse events in non-pregnant participants were related to treatment (one Grade 3; two Grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. Plasma remdesivir PK parameters were comparable between pregnant and non-pregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy.

The kinetics and durability of T-cell responses to SARS-CoV-2 in children are not well-characterized. We studied a cohort of children aged 6 months to 20 years with COVID-19 in whom peripheral blood mononuclear cells (PBMC) and sera were archived at approximately 1, 6, and 12 months post-symptom onset. We compared antibody (N = 85) and T-cell responses (N = 26) to nucleocapsid (N) and spike (S) glycoprotein over time across four age strata: 6 months to 5 years, 5-9, 10-14, and 15-20 years. N-specific antibody responses declined over time, becoming undetectable in 26/32 (81%) children by approximately one year post-infection. Functional breadth of anti-N CD4+ T-cell responses also declined over time and were positively correlated with N-antibody responses (Pearson's r = 0.31, p = 0.008). CD4+ T-cell responses to S displayed greater functional breadth than N in unvaccinated children, and, along with neutralization titers, were stable over time and similar across age strata. Functional profiles of CD4+ T-cell responses against S were not significantly modulated by vaccination. Our data reveal durable, age-independent T-cell immunity to SARS-CoV-2 structural proteins in children over time following COVID-19 infection as well as S-Ab responses overall, in comparison to declining antibody responses to N.

Some individuals may not retain adequate immunity against measles and rubella years after two doses of measles, mumps, and rubella (MMR) vaccination due to vaccine failure. This study aimed to investigate the rates of vaccine failure and seroconversion by administering an MMR booster to young adults. We first assessed measles and rubella antibody levels using the Luminex multiplex assay, VIDAS IgG assay, and plaque reduction neutralization test (PRNT) among individuals aged 18-30 years old who had received two doses of MMR vaccine. Participants with low measles and/or rubella antibody levels as confirmed by VIDAS received an MMR booster. Antibody levels were measured at 1-month post-booster. Among 791 participants, the measles and rubella seroprevalence rates were 94.7% (95% CI: 92.9%-96.0%) and 97.3% (95% CI: 96.0%-98.3%), respectively. Lower seroprevalence rates were observed among older participants. 113 participants who received an MMR booster acquired higher measles and rubella antibody levels at 1-month post-booster compared to baseline. Although measles and rubella vaccine failures were observed among 5.3% and 2.7% of young adults, respectively, an MMR booster triggered a significant antibody response.

We determined the relationships between cytokine expression in sputum and clinical data to characterise and understand Chronic Obstructive Pulmonary Disease (COPD) exacerbations in COPD patients. We measured 30 cytokines in 936 sputum samples, collected at stable state (ST) and exacerbation (EX) visits from 99 participants in the Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) study (NCT01360398, www.clinicaltrials.gov). We determined their longitudinal expression and examined differential expression based on disease status or exacerbation type. Of the cytokines, 17 were suitable for analysis. As for disease states, in EX sputum samples, IL-17A, TNF-α, IL-1β, and IL-10 were significantly increased compared to ST sputum samples, but a logistic mixed model could not predict disease state. As for exacerbation types, bacteria-associated exacerbations showed higher expression of IL-17A, TNF-α, IL-1β, and IL-1α. IL-1α, IL-1β, and TNF-α were identified as suitable biomarkers for bacteria-associated exacerbation. Bacteria-associated exacerbations also formed a cluster separate from other exacerbation types in principal component analysis. Measurement of cytokines in sputum from COPD patients could help identify bacteria-associated exacerbations based on increased concentrations of IL-1α, IL-1β, or TNF-α. This finding may provide a point-of-care assessment to distinguish a bacterial exacerbation of COPD from other exacerbation types.

The outbreak of the COVID-19 pandemic has had a profound impact on the circulation of seasonal respiratory viruses. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in adults hospitalized with severe acute respiratory infection (SARI) during the COVID-19 pandemic. This population-based cohort study included patients aged > 18 years hospitalized for SARI in Brazil between February 2020 and February 2023. The primary outcome was in-hospital mortality. A competing risk analysis was used to account for competing events. In total, 2,159,171 patients were included in the study. SARS-CoV-2 was the predominant virus (98.7%). The cumulative incidence of in-hospital mortality was 33.1%, 31.5%, 21.0%, 18.7%, and 18.6%, for patients positive for SARS-CoV-2, adenovirus, RSV, influenza, and other viruses, respectively. SARS-CoV-2 accounted for 99.3% of the deaths. Older age, male sex, comorbidities, hospitalization in the northern region, and oxygen saturation <95% were the common risk factors for death among all viruses. In this large cohort study, individuals infected with SARS-CoV-2 or adenovirus had the highest risk of mortality. Irrespective of the virus type, older age, male sex, comorbidities, hospitalization in vulnerable regions, and low oxygen saturation were associated with an increased risk of fatality.

Neisseria gonorrhoeae is widespread globally. Primary prevention is unsuccessful and antimicrobial resistance threatens optimal management. There is no specific vaccine and natural infection studies show that N. gonorrhoeae can avoid and suppress immune responses. In addition to extensive variation in expression and specificity of many gonococcal surface antigens, it induces a robust inflammatory response through the Th17 pathway with a large influx of neutrophils and inflammatory cytokines but evades macrophages. The Th1- and Th2-mediated response is suppressed, resulting in low, short-lived antibody titers. Real-world evidence suggests that gonorrhea cases are reduced among recipients of N. meningitidis group B vaccines containing outer membrane vesicles (OMV). Although the first randomized trial of an OMV-containing MenB vaccine against N. gonorrhoeae infection did not show statistically significant vaccine efficacy, ongoing trials might shed further light. Several candidate vaccine antigens for a gonococcal-specific vaccine are being evaluated preclinically but only one has reached clinical trials.