Association of interleukin 7 immunotherapy with lymphocyte counts among patients with severe coronavirus disease 2019 (COVID-19)

This case series examines whether interleukin 7 (IL-7) is associated with restored host protective immunity in patients with severe coronavirus disease 2019 (COVID-19) and immunosuppression

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Efficacy of rituximab in thymoma associated minimal change disease: case report

International audienceBackground: Thymomas have been associated with a broad spectrum of autoimmune diseases. Minimal change disease (MCD) is the most frequent pathological lesion reported. Pathophysiological mechanisms involved in secondary MCD, and linking MCD to thymoma are not yet fully explained, although the hypothesis of T cell dysfunction has been suggested. The fundamental therapeutic principles are steroids and surgical treatment of thymoma, but failures and relapses often require immunosuppressant combinations. Case presentation: A 62-year-old female was admitted in our unit for a nephrotic syndrome associated with a thymoma. The diagnosis of thymoma associated MCD was confirmed by kidney biopsy. After surgical resection of the thymoma and steroid therapy, no remission was observed. Immunosuppressive therapy was then intensified with introduction of rituximab. Here, we report a steroid-resistant nephrotic syndrome secondary to MCD associated thymoma, which achieved complete remission after rituximab therapy. To the best of our knowledge, this is the first report of the use and efficacy of rituximab therapy in this pathology. Conclusions: Our case report suggests that primary and secondary MCD may share similar pathophysiological mechanisms. It does not allow us to draw any conclusions about the mechanism of action of rituximab, but we believe this report argues for the safety and efficacy of rituximab use in thymoma-associated MCD, and therefore constitutes a rationale for future studies

CD95L concatemers highlight different stoichiometries of CD95‐mediated apoptotic and non‐apoptotic pathways

International audienceTo better understand the stoichiometry of CD95L required to trigger apoptotic and nonapoptotic signals, we generated several concatemers from dimer hexamer conjugated via a flexible link (GGGGS)2 . These ligands reveal that although hexameric structure is best cell death, sufficient induce response in CD95-sensitive Jurkat cells. Interestingly, only trimeric forms can implement potent Ca2+ response, suggesting while CD95 aggregation controls implementation signal, both conformation are pathway

Inflamed phenotype of splenic marginal zone B-cell lymphomas with expression of PD-L1 by intratumoral monocytes/macrophages and dendritic cells

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High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia

International audienceBackground: In the Emergency Department (ED), early and accurate recognition of infection is crucial to prompt antibiotic therapy but the initial presentation of patients is variable and poorly characterized. Lymphopenia is commonly associated with bacteraemia and poor outcome in intensive care unit patients. The objective of this retrospective study was to assess the prevalence of community-acquired infection in a cohort of unselected patients admitted to the ED with undifferentiated symptoms and severe lymphopenia.Methods: This is a retrospective single-center study conducted over a 1 year-period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with severe lymphopenia (lymphocyte count < 0.5 G/L) were studied. Patients with hematological or oncological diseases, HIV infection, hepato-cellular deficiency, immunosuppression, or patients over 85 years old were excluded. Diagnoses of infection were validated by an independent adjudication committee. The association between various parameters and infection was assessed using a multivariate logistic regression analysis.Results: Of 953 patients admitted to the ED with severe lymphopenia, 245 were studied (148 men; mean age: 63 ± 19 years). Infection was confirmed in 159 patients (65%) (bacterial: 60%, viral: 30%, other: 10%). Only 61 patients (25%) were referred to the ED for a suspected infection. In the univariate analysis, SIRS criteria (OR: 5.39; 95%CI: 3.04-9.70; p < 0.001) and temperature ≥ 38.3 °C (OR: 10.95; 95%CI: 5.39-22.26; p < 0.001) were strongly associate with infection. In the multivariate analysis, only SIRS criteria (OR: 2.4; 95%CI: 1.48-3.9; p < 0.01) and fever (OR: 3.35; 95%CI: 1.26-8.93; p = 0.016) were independently associated with infection.Conclusions: The prevalence of underlying infection is high in patients admitted to the ED with lymphopenia, irrespective of the reason for admission. Whether lymphopenia could constitute a valuable marker of underlying infection in this clinical setting remains to be confirmed prospectively in larger cohorts

Phagosomal granulocytic ROS in septic patients induce the bacterial SOS response

International audienceSeptic patients with worst clinical prognosis have increased circulating immature granulocytes (IG), displaying limited phagocytosis and reactive oxygen species (ROS) production. Here, we developed an ex vivo model of incubation of human granulocytes, from septic patients or healthy donors, with Escherichia coli. We showed that the ROS production in Sepsis-IG is lower due to decreased activation and protein expression of the NADPH oxidase complex. We also demonstrated that the low level of ROS production and lower phagocytosis of IG in sepsis induce the bacterial SOS response, leading to the expression of the SOS-regulated quinolone resistance gene qnrB2. Without antimicrobial pressure, the sepsis immune response alone may promote antibiotic resistance expression

Immunotherapies for COVID-19: lessons learned from sepsis.

Therapeutic approaches to mitigate the severe acute lung injury associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have rapidly entered clinical trials primarily on anecdotal observations and few clinical studies. Along with the clinical symptoms related to viral invasion, the reported molecular response known as the cytokine storm has attracted the greatest attention, in both the scientific and the lay press, as a cause of organ injury. [...