Background. Data on infections associated with cerebrospinal fluid (CSF) shunts among adults are limited. Therefore, we performed a retrospective stu

BACKGROUND: The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes/macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human leukocyte antigen-DR (mHLA-DR) within the major histocompatibility complex class II reflects a state of immunosuppression, also referred to as injury-associated immunosuppression. As the role of immunosuppression in coronavirus disease 2019 (COVID-19) is currently unclear, we seek to explore the level of mHLA-DR expression in COVID-19 patients. METHODS: In a preliminary prospective monocentric observational study, 16 COVID-19–positive patients (75% male, median age: 68 [interquartile range 59–75]) requiring hospitalization were included. The median Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score in 9 intensive care unit (ICU) patients with acute respiratory failure was 30 (interquartile range 25–32). Standardized quantitative assessment of HLA-DR on monocytes (cluster of differentiation 14+ cells) was performed using calibrated flow cytometry at baseline (ICU/hospital admission) and at days 3 and 5 after ICU admission. Baseline data were compared to hospitalized noncritically ill COVID-19 patients. RESULTS: While normal mHLA-DR expression was observed in all hospitalized noncritically ill patients (n = 7), 89% (8 of 9) critically ill patients with COVID-19–induced acute respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. mHLA-DR expression at admission was significantly lower in critically ill patients (median, [quartiles]: 9280 antibodies/cell [6114, 16,567]) as compared to the noncritically ill patients (30,900 antibodies/cell [26,777, 52,251]), with a median difference of 21,508 antibodies/cell (95% confidence interval [CI], 14,118–42,971), P = .002. Reduced mHLA-DR expression was observed to persist until day 5 after ICU admission. CONCLUSIONS: When compared to noncritically ill hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, indicating a dysfunctional immune response. This immunosuppressive (monocytic) phenotype remained unchanged over the ensuing days after ICU admission. Strategies aiming for immunomodulation in this population of critically ill patients should be guided by an immune-monitoring program in an effort to determine who might benefit best from a given immunological intervention.

Post‐transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein‐Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation and outcome of histologically‐proven PTLD. We included 4’765 patients with a follow‐up duration of 23`807 person‐years (py). Fifty‐seven PTLD cases were identified; 39 (68%) were EBV‐positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years post‐transplant were 3.51; 2.24; 1.75/1’000 py and 0.44; 0.25; 0.29/1’000 py for EBV‐ PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199‐1.436], p=0.264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751‐6.521], p=0.150). However, none of the patients (0/191) who received a rituximab‐containing induction treatment experienced PTLD, but (57/4’574) patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD‐free survival was significantly longer (0.104 years [95% CI 0.077‐0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.

Importance: Vaccine responses are decreased in solid organ transplant (SOT) recipients, and given the complexity of implementation, vaccination programs may be suboptimal. The actual burden of vaccine-preventable infections (VPIs) among SOT recipients remains unclear.Objectives: To assess the incidence rate of VPIs among SOT recipients and to evaluate whether SOT recipients are at increased risk for specific VPIs compared with the general population.Design, Setting, and Participants: This nationwide cohort study used data from the Swiss Transplant Cohort Study on VPIs in individuals who underwent SOT from May 2008 to June 2019 (follow-up until December 2019) and data from the Swiss Federal Office of Public Health on notifiable VPIs in the general population in the same period. Data were analyzed from January 2021 to June 2022.Exposures: Solid organ transplant.Main Outcomes and Measures: The main outcomes were the incidence rate of the following VPIs in SOT recipients: hepatitis A and B, diphtheria, Haemophilus influenzae infection, influenza, measles, mumps, pertussis, pneumococcal disease, poliomyelitis, meningococcal disease, rubella, tetanus, tick-borne encephalitis, and varicella zoster virus infection. Age-adjusted standardized incidence ratios were used to assess whether VPIs occurred more frequently in SOT recipients compared with the general population. For SOT recipients, factors associated with occurrence of VPIs were explored and the associated morbidity and mortality assessed.Results: Of 4967 SOT recipients enrolled (median age, 54 years [IQR, 42-62 years]; 3191 [64.2%] male), 593 (11.9%) experienced at least 1 VPI. The overall VPI incidence rate was higher in the population that underwent SOT (30.57 per 1000 person-years [PY]; 95% CI, 28.24-33.10 per 1000 PY) compared with the general population (0.71 per 1000 PY). The standardized age-adjusted incidence ratio for notifiable VPIs in SOT recipients was higher compared with the general population (27.84; 95% CI, 25.00-31.00). In SOT recipients, influenza and varicella zoster virus infection accounted for most VPI episodes (16.55 per 1000 PY [95% CI, 14.85-18.46 per 1000 PY] and 12.83 per 1000 PY [95% CI, 11.40-14.44 per 1000 PY], respectively). A total of 198 of 575 VPI episodes in the population that underwent SOT (34.4%) led to hospital admission, and the occurrence of a VPI was associated with an increased risk for death and/or graft loss (hazard ratio, 2.44; 95% CI, 1.50-3.99; P = .002). In multivariable analysis, age 65 years or older at the time of transplant (incidence rate ratio [IRR], 1.29; 95% CI, 1.02-1.62) and receipt of a lung (IRR, 1.77; 95% CI, 1.38-2.26) or a heart (IRR, 1.40; 95% CI, 1.05-1.88) transplant were associated with an increased risk of VPI occurrence.Conclusions and Relevance: In this study, 11.9% of SOT recipients experienced VPIs, and the incidence rate was higher than in the general population. There was significant morbidity and mortality associated with these infections in the population that underwent SOT, which highlights the need for optimizing immunization strategies.

In this study, we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI (n = 1404; 59%), (ii) colonization only (n = 353; 15%), (iii) occasional UTI with 1–2 episodes (n = 456; 19%), and (iv) recurrent UTI with ≥3 episodes (n = 155; 7%). One‐year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7‐10 ml/min lower eGFR at year one (44 ml/min vs. 54, 53, and 51 ml/min; p < .001). UTI phenotypes had no impact on long‐term patient survival (p = .33). However, patients with recurrent UTI demonstrated a 10% lower long‐term death‐censored allograft survival (p < .001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death‐censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53–7.68, p < .001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one‐year eGFR and lower long‐term death‐censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed.