Adequacy to immunosuppression management guidelines in kidney transplant recipients with severe COVID-19 pneumonia: a practice survey.

Introduction: Coronavirus disease 2019 (COVID-19) poses an important risk of morbidity and of mortality, in patients after solid organ transplantation. Recommendations have been issued by various transplantation societies at the national and European level to manage the immunosuppressive (IS) regimen upon admission to intensive care unit (ICU). Method: The aim of this study was to evaluate the adequacy of IS regimen minimization strategy in kidney transplant recipients hospitalized in an ICU for severe COVID-19, in relation to the issued recommendations. Results: The immunosuppressive therapy was minimized in all patients, with respectively 63% and 59% of the patients meeting the local and european recommendations upon admission. During ICU stay, IS was further tapered leading to 85% (local) and 78% (european) adequacy, relative to the guidelines. The most frequent deviation was the lack of complete withdrawal of mycophenolic acid (22%). Nevertheless, the adequacy/inadequacy status was not associated to the ICU- or one-year-mortality. Discussion: In this single-center cohort, the only variable associated with a reduction in mortality was vaccination, emphasizing that the key issue is immunization prior to infection, not restoration of immunity during ICU stay.

Amoxicillin and Ceftriaxone: A Synergistic Association Against Listeria monocytogenes.

Among 15 strains of Listeria monocytogenes tested, a synergy between amoxicillin and ceftriaxone was observed in 14 (93%) according to minimal inhibitory concentration strips and 12 (80%) per the checkerboard methods, as well as for 2 of the 3 strains tested by the time-killing curve. This association may be an alternative treatment for listeriosis in the future.

Acyclovir treatment of varicella-zoster virus meningeal infections and acute kidney injury: a multicentre case series study.

BACKGROUND: Systematic treatment with intravenous acyclovir is usually given when varicella zoster virus (VZV) DNA is isolated in cerebrospinal fluid (CSF), indicating central nervous system (CNS) involvement. Our study aimed to describe therapeutic management and acute kidney injury (AKI) occurrence during acyclovir treatment of VZV infection with CNS involvement. METHODS: Multicentre, retrospective study including all patients from 2010 to 2022 with VZV DNA in CSF. Patient management and outcomes were compared according to clinical presentation and indications for intravenous acyclovir: i) definite (encephalitis, myelitis or stroke, peripheral nervous system (PNS) with ≥ 2 roots, herpes zoster ≥ 3 dermatomes, immunosuppression), ii) questionable (1 or 2 dermatomes) or iii) no indication (other situations). RESULTS: 154 patients were included (median age 66 (interquartile range 43-77), 87 (56%) males); 60 (39%) had encephalitis, myelitis or stroke, 35 (23%) had PNS involvement, 37 (24%) had isolated meningitis, 14 (9%) had isolated cutaneous presentation, and 8 (5%) had other presentations. Overall, 128 (83%) received intravenous acyclovir for more than 72 h. AKI occurred in 57 (37%) patients. Finally, 42 (27%) and 25 (16%) patients had respectively no or a questionable indication for intravenous acyclovir, while 29 (69%) and 23 (92%) of them received it for more than 72 h, with AKI in 13 (35%) and 13 (52%) patients, respectively. In-hospital mortality was 12% (n = 18), and no deaths were reported in isolated meningitis. CONCLUSIONS: Intravenous acyclovir is widely prescribed when VZV DNA is isolated in CSF, regardless of the clinical presentation, with a high rate of AKI. Further studies are needed to better define the value of intravenous acyclovir in isolated VZV meningitis.

Characteristics and incidence of infections in patients with multiple myeloma treated by bispecific antibodies: a national retrospective study.

OBJECTIVES: Bispecific antibodies (BsAbs) are an effective treatment used in relapsed or refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appear to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors, and outcomes of infections in patients treated with BsAb are still needed. METHODS: A retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration. RESULTS: Among 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38-3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3-0.94 and HR = 0.65; 95% CI, 0.46-0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27-3.19). DISCUSSIONS: The implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS.

Neutralizing IFN-γ autoantibodies are rare and pathogenic in HLA-DRB1*15:02 or 16:02 individuals.

BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Union's Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea & Bowery Advisory Group, William E. Ford, General Atlantic's Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantic's Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste d'accueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS).

The evolution of lung computed tomography findings in COVID-19 from 2020 to 2023: more signs of co-infection.

Significant changes were observed in the lung imaging of hospitalised COVID-19 patients from 2020 to 2023, with the emergence of more signs of co-infection https://bit.ly/3TaQlJ2.

CMV Infection and Lymphopenia: Warning Markers of Pneumocystis Pneumonia in Kidney Transplant Recipients.

Pneumocystis pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric, case-control study including all KTR at the Dijon University Hospital (France) with a diagnosis of PcP between 2005 and 2022 (cases), and matched control KTR with no history of PcP (3 controls/case). Among all 1,135 KTR, 57 cases (5%) and 169 matched-controls were included. PcP was associated with 18% mortality. Compared to controls, cases were older, with a higher immunological risk, and CMV infection was more frequent in the year preceding the occurrence of PcP (23% vs. 4%; p < 0.001). As early as 1 year before PcP, lymphocyte counts were lower and serum creatinine levels were higher in cases, but immunosuppressive regimens were not significantly different. Multivariable analysis identified lymphocyte count, serum creatinine level, being treated by immunosuppressive therapy other than anti-rejection drugs, and CMV infection in the year preceding the time PcP as independently associated with the occurrence of PcP. PcP was associated with an increased risk of subsequent chronic rejection (27% vs. 3%; p = 0.001) and return to dialysis (20% vs. 3%; p = 0.002). The occurrence of CMV infection and a low lymphocyte count could redefine the indications for continuation or reinitiation of anti-Pneumocystis prophylaxis.

Legionnaires Disease in Solid Organ Transplant Recipients: A Decade-Long Nationwide Study in France.

BACKGROUND: Legionnaires disease (LD) is a rare, life-threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell-mediated immunity such as solid organ transplant recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described. RESEARCH QUESTION: What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients? STUDY DESIGN AND METHODS: In this 10-year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU. RESULTS: One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground-glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30-day and 12-month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12-month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022). INTERPRETATION: LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis.

Children Hospitalized With Respiratory Syncytial Virus Infection: A Pre Versus Late COVID-19 Pandemic Comparison.

Our study aimed to compare children under 5 years hospitalized with respiratory syncytial virus in prepandemic and late-pandemic periods. We included 209 children at the Dijon University Hospital (France). We observed a nearly 3-fold increase in the number of cases in the late period, with older children, but less frequently requiring intensive care. These observations could help prepare a new pandemic.

Pneumococcal pneumonia and endotoxemia: An experimental and clinical reappraisal.

BACKGROUND: Circulating endotoxins could result from bacterial digestive translocation during sepsis, thus contributing to uncontrolled systemic inflammation, leading in turn to organ dysfunction. We addressed this issue in the setting of severe pneumococcal pneumonia. METHODS: Endotoxemia was measured in a clinically relevant rabbit model of ventilated pneumococcal pneumonia and in 110 patients with bacteraemic pneumonia, using a patented mass spectrometry (LC-MS/MS) method for detection of 3-OH fatty acids (C10, C12, C14, C16 and C18), which are molecules bound to the lipid A motif of LPS. RESULTS: Whereas higher levels of systemic inflammation and organ dysfunctions were found, there was no significant difference in lipopolysaccharide concentrations when infected rabbits were compared to non-infected ones, or when patients were compared to healthy volunteers. CONCLUSIONS: Seemingly, endotoxins do not drive the overwhelming inflammation associated with severe forms of pneumococcal pneumonia.

Role of the interstitium during septic shock: a key to the understanding of fluid dynamics?

BACKGROUND: While not traditionally included in the conceptual understanding of circulation, the interstitium plays a critical role in maintaining fluid homeostasis. Fluid balance regulation is a critical aspect of septic shock, with a well-known association between fluid balance and outcome. The regulation of transcapillary flow is the first key to understand fluid homeostasis during sepsis. MAIN TEXT: Capillary permeability is increased during sepsis, and was classically considered to be necessary and sufficient to explain the increase of capillary filtration during inflammation. However, on the other side of the endothelial wall, the interstitium may play an even greater role to drive capillary leak. Indeed, the interstitial extracellular matrix forms a complex gel-like structure embedded in a collagen skeleton, and has the ability to directly attract intravascular fluid by decreasing its hydrostatic pressure. Thus, interstitium is not a mere passive reservoir, as was long thought, but is probably major determinant of fluid balance regulation during sepsis. Up to this date though, the role of the interstitium during sepsis and septic shock has been largely overlooked. A comprehensive vision of the interstitium may enlight our understanding of septic shock pathophysiology. Overall, we have identified five potential intersections between septic shock pathophysiology and the interstitium: 1. increase of oedema formation, interacting with organ function and metabolites diffusion; 2. interstitial pressure regulation, increasing transcapillary flow; 3. alteration of the extracellular matrix; 4. interstitial secretion of inflammatory mediators; 5. decrease of lymphatic outflow. CONCLUSIONS: We aimed at reviewing the literature and summarizing the current knowledge along these specific axes, as well as methodological aspects related to interstitium exploration.

Aspergillus colonisation in severe community-acquired pneumonia: not just a mere colonisation.

In patients with severe community-acquired pneumonia, detection of Aspergillus is associated with a mortality rate surpassing 50%, irrespective of whether it is defined as invasion or colonisation https://bit.ly/46PMk1f.

Healing Treatments in COVID-19 Patients: A Narrative Review.

Since December 2019, many drugs have been evaluated or advocated as potential treatments of SARS-CoV-2 induced disease (COVID-19), including many repositioned drugs and some others specifically developed for these diseases. They can be roughly classified into three categories according to their main mechanism of action (passive immunization, direct antivirals, and anti-inflammatory treatments), and their use depends on the stage of the disease. Despite often promising preclinical data, most of the treatments evaluated failed to show a significant clinical benefit. In addition, a few others have seen their effectiveness affected by the occurrence of SARS-CoV-2 variants and sub-variants. Herein, the aim of this article is to take stock of the data available as of the 14th of July 2022, concerning the specific healing options evaluated for patients suffering from COVID-19. We focus particularly on healing treatments of COVID-19 and do not deal with preventive treatments such as vaccine. Associated therapies such as venous thromboembolism prophylaxis are not detailed since they are covered in a specific chapter of this issue. Passive immunization, especially through monoclonal antibodies, showed a positive impact on the clinical evolution, whether in outpatients or inpatients without oxygen supply. However, their effectiveness strongly depends on the type of SARS-CoV-2 variant, and often decreases or even vanishes with the most recent variants. Among direct antiviral treatments, ritonavir-boosted nirmatrelvir appears to currently be the cornerstone in the management of early infections, but its use may be limited by drug interactions. Remdesivir remains as an alternative in this situation, even though it is potentially less convenient. Anti-inflammatory treatments have often been shown to be the most effective in inpatients with oxygen supply. Dexamethasone is now a cornerstone of management of these patients. Added tocilizumab seems beneficial in the case of hyper inflammation. JAK inhibitors and anakinra have also gained an interest in some studies. As a conclusion of this narrative review, the best treatment strategy has yet to be defined and is likely to evolve in the future, not only because many other drugs are still under development and evaluation, but also because of the viral epidemics and epidemiology evolution.

Dynamic full-field optical coherence tomography for live-cell imaging and growth-phase monitoring in Aspergillus fumigatus.

Introduction: The diagnosis of cutaneous manifestations of deep mycoses relies on both histopathological and direct examinations. Yet, the current diagnostic criteria cannot prevent missed cases, including invasive aspergillosis, which requires the development of a novel diagnostic approach and imaging tools. We recently introduced the use of dynamic full-field optical coherence tomography (D-FF-OCT) in fungal diagnostics with a definition approaching that of conventional microscopy and the ability to return metabolic information regarding different fungal species. The present work focuses on subcellular dynamics and live-cell imaging of Aspergillus fumigatus with D-FF-OCT to follow the fungal growth stages. Methods: The A. fumigatus ATCC 204305 quality-control strain was used for all imaging experiments, following incubation times varying between 24 and 72 h at 30°C in a humidified chamber on Sabouraud dextrose agar. Fungal growth was subsequently monitored with D-FF-OCT for up to 5 h at room temperature and following the pharmacological stress of either voriconazole, amphotericin B, or caspofungin gradient concentration. Results: D-FF-OCT images allow not only the visualization of intracellular trafficking of vacuoles but also an evolving dynamic segmentation of conidiophores depending on the chronological development and aging of the hyphae or the effect of antifungal treatment. The same applies to conidial heads, with the most intense D-FF-OCT signal coming from vesicles, revealing a changing dynamic within a few hours only, as well as complete extinction following subsequent drying of the Sabouraud dextrose agar. Discussion: These results provide additional data on the ability of D-FF-OCT to monitor some of the main life cycle processes, dynamics, and intracellular trafficking of vacuoles in A. fumigatus, with or without the effect of pharmacological stress. Such complementary metabolic information could help both clinicians and microbiologists in either mechanistic studies toward experimental mycology or the development of a potential D-FF-OCT-guided diagnosis of superficial fungal infections.

Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study.

BACKGROUND: The leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data show that the combination of corticosteroids/third-generation cephalosporins and the non-lytic antibiotic, daptomycin, has synergistic effects with (1) a rapid cerebrospinal fluid sterilisation, (2) less brain damages and (3) less loss of cognitive performances. Despite these encouraging results, daptomycin has never been evaluated in adult patients with pneumococcal meningitis. METHODS AND ANALYSIS: The AddaMAP trial is a phase II, open-label, Simon's two-stage, multicentre trial that has been designed to assess the efficacy and safety of adding daptomycin (10 mg/kg/d for 8 days) to the recommended treatment (corticosteroids+third generation cephalosporin) in adults with confirmed pneumococcal meningitis. The main endpoint is the disability-free survival (defined as modified Rankin Scale mRS≤2) at day 30. Secondary outcomes are overall mortality, disability at D30 and D90 (mRS, Glasgow Coma Scale and Glasgow Outcome Scales, mini-mental score), hearing loss (Hearing Handicap Inventory Test at D30 and D90, routine audiometric test and Hearing-it test at D30), and quality of life (12-item Short Form Survey and WHO QOL BREF). Seventy-two analysable patients are required. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of the IDF 1 of the ethics committee on 16 January 2018, and authorisation was obtained from the Agence Nationale de Securité des Médicaments et des Produits de Santé on 22 September 2017. The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03480191.

Delayed diagnosis of pneumonia in the emergency department: factors associated and prognosis.

Introduction: Whether a delayed diagnosis of community-acquired pneumonia (CAP) in the emergency department (ED) is associated with worse outcome is uncertain. We sought factors associated with a delayed diagnosis of CAP in the ED and those associated with in-hospital mortality. Methods: Retrospective study including all inpatients admitted to an ED (Dijon University Hospital, France) from 1 January to 31 December 2019, and hospitalized with a diagnosis of CAP. Patients diagnosed with CAP in the ED (n = 361, early diagnosis) were compared with those diagnosed later, in the hospital ward, after the ED visit (n = 74, delayed diagnosis). Demographic, clinical, biological and radiological data were collected upon admission to the ED, as well as administered therapies and outcomes including in-hospital mortality. Results: 435 inpatients were included: 361 (83%) with an early and 74 (17%) with a delayed diagnosis. The latter less frequently required oxygen (54 vs. 77%; p < 0.001) and were less likely to have a quick-SOFA score ≥ 2 (20 vs. 32%; p = 0.056). Absence of chronic neurocognitive disorders, of dyspnea, and of radiological signs of pneumonia were independently associated with a delayed diagnosis. Patients with a delayed diagnosis less frequently received antibiotics in the ED (34 vs. 75%; p < 0.001). However, a delayed diagnosis was not associated with in-hospital mortality after adjusting on initial severity. Conclusion: Delayed diagnosis of pneumonia was associated with a less severe clinical presentation, lack of obvious signs of pneumonia on chest X-ray, and delayed antibiotics initiation, but was not associated with worse outcome.

Endotracheal tube biofilm in critically ill patients during the COVID-19 pandemic : description of an underestimated microbiological compartment.

Biofilm (BF) growth is believed to play a major role in the development of ventilator-associated pneumonia (VAP) in the intensive care unit. Despite concerted efforts to understand the potential implication of endotracheal tube (ETT)-BF dispersal, clinically relevant data are lacking to better characterize the impact of its mesostructure and microbiological singularity on the occurrence of VAP. We conducted a multicenter, retrospective observational study during the third wave of the COVID-19 pandemic, between March and May 2021. In total, 64 ETTs collected from 61 patients were included in the present BIOPAVIR study. Confocal microscopy acquisitions revealed two main morphological aspects of ETT-deposited BF: (1) a thin, continuous ribbon-shaped aspect, less likely monobacterial and predominantly associated with Enterobacter spp., Streptococcus pneumoniae or Viridans streptococci, and (2) a thicker, discontinuous, mushroom-shaped appearance, more likely characterized by the association of bacterial and fungal species in respiratory samples. The microbiological characterization of ETT-deposited BF found higher acquired resistance in more than 80% of analyzed BF phenotypes, compared to other colonization sites from the patient's environment. These findings reveal BF as a singular microbiological compartment, and are of added clinical value, with a view to future ETT-deposited BF-based antimicrobial stewardship in critically ill patients. Trial registration NCT04926493. Retrospectively registered 15 June 2021.

T-cell immune response predicts the risk of critical SARS-Cov2 infection in hospitalized COVID-19 patients.

INTRODUCTION: This study aimed to identify markers of disease worsening in patients hospitalized for SARS-Cov2 infection. PATIENTS AND METHODS: Patients hospitalized for severe recent-onset (<1 week) SARS-Cov2 infection were prospectively included. The percentage of T-cell subsets and plasma IL-6 at admission (before any steroid therapy) were compared between patients who progressed to a critical infection and those who did not. RESULTS: Thirty-seven patients (18 men, 19 women) were included; 11 (30%) progressed to critical infection. At admission, the critical infection patients were older (P = 0.021), had higher creatinine levels (P = 0.003), and decreased percentages of circulating B cells (P = 0.04), T cells (P = 0.009), and CD4+ T cells (P = 0.004) than those with a favorable course. Among T cell subsets, there was no significant difference between the two groups except for the percentage of Th17 cells, which was two-fold higher in patients who progressed to critical infection (P = 0.028). Plasma IL-6 at admission was also higher in this group (P = 0.018). In multivariate analysis, the percentage of circulating Th17 cells at admission was the only variable associated with higher risk of progression to critical SARS-Cov2 infection (P = 0.021). CONCLUSION: This study suggests that an elevated percentage of Th17 cells in patients hospitalized for SARS-Cov2 infection is associated with an increased risk of progression to critical disease. If these data are confirmed in a larger study, this marker could be used to better target the population of patients in whom tocilizumab could decrease the risk of progression to critical COVID-19.

Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response.

Introduction: While QuantiFERON-TB gold (QFT) is frequently used, little attention is paid to the mitogen response. How it could be impacted and associated with outcomes is poorly known. Methods: Retrospective, case-control study in hospitalized patients who underwent QFT testing in two hospitals between 2016 and 2019. We defined two groups of cases with either negative [interferon (IFN)-γ ≤ 0.5 IU/ml, official threshold] or weak (0.5-2 IU/ml) mitogen response, and one group of controls with normal (>2 IU/ml) mitogen response. Results: A total of 872 patients were included. An ongoing infection was independently associated with both a negative (RR = 4.34; 95% CI = 2.94-6.41) and a weak mitogen response (RR = 2.44; 95% CI = 1.66-3.58). Among tuberculosis patients, a weak mitogen response was associated with a false-negative QFT result (75%) compared to a normal response (20%). Decreasing mitogen response (normal, weak and negative, respectively) was associated with increasing length of hospital stay [median (interquartile range) 5 (3-13), 11 (5-21) and 15 (10-30) days; p < 0.001] and increasing hospital mortality (3, 7, and 15%; p < 0.001). Conclusion: Clinicians should take notice of the mitogen response since IFN-γ concentrations lower than <2 IU/ml were associated with false-negative QFT results in tuberculosis patients, independently associated with ongoing infections, and could be associated with worse prognosis.

Dynamic full-field optical coherence tomography as complementary tool in fungal diagnostics.

Histopathology and microscopic examination of infected tissue are the gold standards to prove the diagnosis of invasive fungal infection (IFI). Yet, they suffer from essential limitations that hamper rapid diagnosis and require the future development of new imaging tools dedicated to fungal diagnostics. To this end, the present work introduces the first use of dynamic full-field optical coherence tomography (D-FF-OCT) for the visualization of microscopic filamentous fungi. Data collected from the observation of three different fungal species (Nannizzia gypsea, Aspergillus fumigatus and Rhizopus arrhizus) confirm the ability of D-FF-OCT to visualize not only the main structures of all selected fungal species (hyphae, spores, conidia, sporulating structures), but also the metabolic activity of the organisms, which could provide additional help in the future to better characterize the signature of each fungal structure. These results demonstrate how D-FF-OCT could serve as potential complementary tool for rapid diagnosis of IFI in both intensive and non-intensive care units.