Human adenoviral (HAdV) chronic arthritis expands the infectious spectrum of primary agammaglobulinemia.

Inborn errors of immunity (IEI) are a heterogeneous entity with an increasing number of late diagnoses. Besides infections, inflammatory manifestations are a growing part of the clinical landscape of IEI. These complications are of unknown causes and often lead to the prescription of immunosuppressive agents that worsen the underlying immune defect. We here report the case of an adult patient diagnosed with chronic Human Adenovirus C-1 arthritis in the setting of primary agammaglobulinemia. Metagenomic next-generation sequencing led to the correct diagnosis and high-dose intravenous immunoglobulins resulted in complete recovery. This observation gives new insights into adenoviral immunity and underlines the importance of metagenomics in the diagnosis of inflammatory manifestations in immunocompromised patients.

BMI and pneumonia outcomes in critically ill covid-19 patients: An international multicenter study.

OBJECTIVE: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19. METHODS: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively. RESULTS: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64]). CONCLUSIONS: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.

Phenotypic and functional changes induced in hematopoietic stem/progenitor cells after gamma-ray radiation exposure.

Ionizing radiation (IR) exposure causes rapid and acute bone marrow (BM) suppression that is reversible for nonlethal doses. Evidence is accumulating that IR can also provoke long-lasting residual hematopoietic injury. To better understand these effects, we analyzed phenotypic and functional changes in the stem/progenitor compartment of irradiated mice over a 10-week period. We found that hematopoietic stem cells (HSCs) identified by their repopulating ability continued to segregate within the Hoechst dye excluding "side population (SP)" early after IR exposure. However, transient phenotypic changes were observed within this cell population: Sca-1 (S) and c-Kit (K) expression levels were increased and severely reduced, respectively, with a concurrent increase in the proportion of SP(SK) cells positive for established indicators of the presence of HSCs: CD150 and CD105. Ten weeks after IR exposure, expression of Sca-1 and c-Kit at the SP cell surface returned to control levels, and BM cellularity of irradiated mice was restored. However, the c-Kit(+)Sca-1(+)Lin(-/low) (KSL) stem/progenitor compartment displayed major phenotypic modifications, including an increase and a severe decrease in the frequencies of CD150(+)Flk2(-) and CD150(-)Flk2(+) cells, respectively. CD150(+) KSL cells also showed impaired reconstituting ability, an increased tendency to apoptosis, and accrued DNA damage. Finally, 15 weeks after exposure, irradiated mice, but not age-matched controls, allowed engraftment and significant hematopoietic contribution from transplanted congenic HSCs without additional host conditioning. These results provide novel insight in our understanding of immediate and delayed IR-induced hematopoietic injury and highlight similarities between HSCs of young irradiated and old mice.

High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation.

OBJECTIVE: The COVID-19 pandemic is rapidly spreading worldwide, notably in Europe and North America where obesity is highly prevalent. The relation between obesity and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has not been fully documented. METHODS: This retrospective cohort study analyzed the relationship between clinical characteristics, including BMI, and the requirement for invasive mechanical ventilation (IMV) in 124 consecutive patients admitted in intensive care for SARS-CoV-2 in a single French center. RESULTS: Obesity (BMI > 30) and severe obesity (BMI > 35) were present in 47.6% and 28.2% of cases, respectively. Overall, 85 patients (68.6%) required IMV. The proportion of patients who required IMV increased with BMI categories (P < 0.01, χ2 test for trend), and it was greatest in patients with BMI > 35 (85.7%). In multivariate logistic regression, the need for IMV was significantly associated with male sex (P < 0.05) and BMI (P < 0.05), independent of age, diabetes, and hypertension. The odds ratio for IMV in patients with BMI > 35 versus patients with BMI < 25 was 7.36 (1.63-33.14; P = 0.02). CONCLUSIONS: The present study showed a high frequency of obesity among patients admitted in intensive care for SARS-CoV-2. Disease severity increased with BMI. Obesity is a risk factor for SARS-CoV-2 severity, requiring increased attention to preventive measures in susceptible individuals.

Discontinuation of antimicrobial therapy in adult neutropenic haematology patients: A prospective cohort.

OBJECTIVES: Antibiotics for febrile neutropenia (FN) in acute myeloid leukaemia (AML) patients undergoing intensive chemotherapy are usually maintained until neutropenia resolution, because of the risk of uncontrolled sepsis in this vulnerable population. This leads to unnecessarily prolonged antimicrobial therapy. METHODS: Based on ECIL-4 recommendations, we modified our management strategy and discontinued antibiotics after a pre-established duration in patients treated for a first episode of FN between August 2014 and October 2017. RESULTS: Antibiotics were stopped during 62 FN episodes, and maintained in the control group (n = 13). Median age of patients was 54 years. A total of 39 (63%) patients received induction and 23 (37%) consolidation chemotherapy; 36 (58%) patients had fever of unknown origin. Median neutropenia length was 26 days (IQR 24-30). Antibiotics were started at day 9 (IQR 5-13). Most patients received piperacillin-tazobactam (56%) or cefepime (32%). Antimicrobial therapy was longer in the control group than in the policy compliant group, 10 (IQR 7-16) vs. 19 days (IQR 15-23), P = 0.0001. After antibiotics discontinuation, 20% patients experienced fever recurrence, within 5.5 days (IQR 3-7.5). None of these febrile episodes were severe and 80% patients remained afebrile, with neutrophil recovery occurring within 5 days (IQR 2-8.5). Overall, 287 antibiotics days were spared; this represents 49% of all days with antibiotics. No patient had died at day 30 from intervention; six died during late follow-up, two from graft-versus-host disease and four from relapsed or refractory leukaemia. CONCLUSIONS: Discontinuing antibiotics in neutropenic AML patients treated for a first episode of FN is safe, and results in significant antibiotic sparing.