Influenza A virus exploits transferrin receptor recycling to enter host cells.

Influenza A virus (IAV) enters host cells mostly through clathrin-dependent receptor-mediated endocytosis. A single bona fide entry receptor protein supporting this entry mechanism remains elusive. Here we performed proximity ligation of biotin to host cell surface proteins in the vicinity of attached trimeric hemagglutinin-HRP and characterized biotinylated targets using mass spectrometry. This approach identified transferrin receptor 1 (TfR1) as a candidate entry protein. Genetic gain-of-function and loss-of-function experiments, as well as in vitro and in vivo chemical inhibition, confirmed the functional involvement of TfR1 in IAV entry. Recycling deficient mutants of TfR1 do not support entry, indicating that TfR1 recycling is essential for this function. The binding of virions to TfR1 via sialic acids confirmed its role as a directly acting entry factor, but unexpectedly even headless TfR1 promoted IAV particle uptake in trans. TIRF microscopy localized the entering virus-like particles in the vicinity of TfR1. Our data identify TfR1 recycling as a revolving door mechanism exploited by IAV to enter host cells.

A high-throughput microfluidic nanoimmunoassay for detecting anti-SARS-CoV-2 antibodies in serum or ultralow-volume blood samples.

Novel technologies are needed to facilitate large-scale detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies in human blood samples. Such technologies are essential to support seroprevalence studies and vaccine clinical trials, and to monitor quality and duration of immunity. We developed a microfluidic nanoimmunoassay (NIA) for the detection of anti-SARS-CoV-2 IgG antibodies in 1,024 samples per device. The method achieved a specificity of 100% and a sensitivity of 98% based on the analysis of 289 human serum samples. To eliminate the need for venipuncture, we developed low-cost, ultralow-volume whole blood sampling methods based on two commercial devices and repurposed a blood glucose test strip. The glucose test strip permits the collection, shipment, and analysis of 0.6 µL of whole blood easily obtainable from a simple finger prick. The NIA platform achieves high throughput, high sensitivity, and specificity based on the analysis of 289 human serum samples, and negligible reagent consumption. We furthermore demonstrate the possibility to combine NIA with decentralized and simple approaches to blood sample collection. We expect this technology to be applicable to current and future SARS-CoV-2 related serological studies and to protein biomarker analysis in general.

Prevalence of Post-Coronavirus Disease Condition 12 Weeks After Omicron Infection Compared With Negative Controls and Association With Vaccination Status.

BACKGROUND: Post-coronovirus disease (COVID) symptoms can persist several months after severe acute respiratory syndrome coronavirus 2 infection. Little is known, however, about the prevalence of post-COVID condition following infections from Omicron variants and how this varies according to vaccination status. This study evaluates the prevalence of symptoms and functional impairment 12 weeks after an infection by Omicron variants (BA.1 and BA.2) compared with negative controls tested during the same period. METHODS: Outpatient individuals who tested positive or negative for COVID-19 infection between December 2021 and February 2022 at the Geneva University Hospitals were followed 12 weeks after their test date. RESULTS: Overall, 11.7% of Omicron cases had symptoms 12 weeks after the infection compared with 10.4% of individuals who tested negative during the same period (P < .001), and symptoms were much less common in vaccinated versus nonvaccinated individuals with Omicron infection (9.7% vs 18.1%; P < .001). There were no significant differences in functional impairment at 12 weeks between Omicron cases and negative controls, even after adjusting for multiple potential confounders. CONCLUSIONS: The differential prevalence of post-COVID symptoms and functional impairment attributed to Omicron BA.1 and BA.2 infection is low when compared with negative controls. Vaccination is associated with lower prevalence of post-COVID symptoms.

A Case of Mpox Reinfection.

A healthy young man first diagnosed with mpox in May 2022 presented again in November 2022 with anal proctitis and a positive polymerase chain reaction on a rectal swab for Monkeypox virus after a recent trip to Brazil, where he engaged in condomless sexual intercourse with multiple male partners.

The present and future of blood virome in allogeneic hematopoietic cell transplant recipients.

PURPOSE OF REVIEW: Allogeneic hematopoietic cell transplantation (allogeneic HCT) is a highly effective therapy for a broad range of hematological diseases and its use is increasing worldwide. Despite advances in antiviral prophylaxis and treatment, viral infections are still one of the leading causes of post-HCT morbidity and mortality. In this patient population, metagenomic next-generation sequencing (mNGS) revealed a much larger diversity of viruses than previously suspected via the targeted screening approach. In the context of profound immunosuppression, these viral infections may cause transient viremia or protracted replication and potentially be associated with yet unrecognized or unspecific clinical manifestations. On the contrary, by constantly interacting with the immune system, viral infections may have a significant impact on posttransplant outcomes. Here, we review the latest advances in research assessing the role of the blood virome in the development of post-HCT complications. RECENT FINDINGS: Research efforts are under way to uncover the potential role of several previously undetected viruses in the development of allogeneic HCT complications and their impact on transplant outcomes. SUMMARY: The identification of viral actors impacting post-HCT morbidity and survival is key to optimize monitoring and infection prevention/treatment strategies.

Viremia as a predictor of absence of serious bacterial infection in children with fever without source.

Most children with fever without source (FWS) require diagnostic laboratory tests to exclude a serious bacterial infection (SBI), often followed by admission and empirical antibiotics. As febrile children with a viral infection are less likely to have a SBI, identifying patients with systemic viral infection could contribute to exclude SBI. We evaluated whether the presence of virus in the blood could be used as a biomarker to rule out SBI. Children < 3 years old with FWS were prospectively enrolled and had real-time (reverse-transcription) PCR performed on the blood for adenovirus, enterovirus, parechovirus, and HHV6. 20/135 patients had SBI, and in 47/135, at least one virus was detected in the blood. Viremia had a higher sensitivity and negative predictive value (90% and 96%) to rule out SBI compared to CRP (65% and 93%) and PCT (55% and 90%). The odds ratio (OR) for the presence of SBI among non-viremic patients was 5.8 (p = 0.0225), compared to 5.5 for CRP ≥ 40 mg/l (p = 0.0009) and 3.7 for PCT ≥ 0.5 ng/mL (0.0093). This remained significant after adjusting for CRP and PCT (OR 5.6 and 5.9, respectively; p = 0.03 for both). Area under the ROC curve for CRP and PCT were 0.754 and 0.779, respectively, but increased to 0.803 and 0.832, respectively, when combined with viremia. CONCLUSION: The presence of viremia had a better performance than commonly used biomarkers to rule-out SBI and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS. Larger studies should evaluate the role of point-of-care testing of viruses by (revere-transcription) PCR in the plasma in management algorithms of children with FWS. WHAT IS KNOWN: • Most children with FWS have a viral infection, but up to 15% have a SBI; most require laboratory tests, and many admission and empirical antibiotics. • Children with a viral infection are less likely to have a SBI. WHAT IS NEW: • Children with a systemic viral infection are less likely to have an SBI. • Viremia is a better predictor of absence of SBI than commonly used biomarkers and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS.

Non-Steroidal Estrogens Inhibit Influenza Virus by Interacting with Hemagglutinin and Preventing Viral Fusion.

Influenza virus is one of the main causes of respiratory infections worldwide. Despite the availability of seasonal vaccines and antivirals, influenza virus infections cause an important health and economic burden. Therefore, the need to identify alternative antiviral strategies persists. In this study, we identified non-steroidal estrogens as potent inhibitors of influenza virus due to their interaction with the hemagglutinin protein, preventing viral entry. This activity is maintained in vitro, ex vivo, and in vivo. Therefore, we found a new domain to target on the hemagglutinin and a class of compounds that could be further optimized for influenza treatment.

[Monkeypox: a new emerging infectious threat?] / Variole du singe : une nouvelle menace infectieuse émergente ?

Monkeypox, caused by the mpox virus, is an emerging infectious eruptive disease, endemic in some African countries, that spread rapidly worldwide from May to December 2022. This new epidemic differs from the previous African ones by its mode of transmission, essentially through intimate contact and/or sexual intercourse, and by the fact that in more than 90 % of cases it affects men who have sex with men. Severe forms of the disease, responsible for significant mortality, have been described in immunosuppressed patients. A third-generation vaccine is available for high-risk groups and several international randomized controlled studies are evaluating the efficacy of tecovirimat. While it is impossible to know whether we will see a new epidemic wave in 2023, only a collective commitment to information sharing will ensure adequate surveillance and an appropriate and rapid preventive and therapeutic answer.

La variole du singe, due au virus mpox, est une maladie infectieuse éruptive émergente, endémique dans certains pays d'Afrique, qui s'est étendue mondialement de mai à décembre 2022. Cette nouvelle épidémie se distingue des précédentes, africaines, par son mode de transmission, essentiellement des contacts intimes et/ou des rapports sexuels, et par le fait qu'elle touche dans plus de 90 % des cas des hommes ayant des relations sexuelles avec d'autres hommes. Des formes graves, responsables d'une mortalité significative, ont été décrites chez des patients immunodéprimés. Un vaccin de troisième génération est disponible pour les groupes à haut risque et plusieurs études internationales randomisées et contrôlées évaluent l'efficacité du técovirimat. S'il est impossible d'exclure ou d'affirmer une nouvelle explosion épidémique en 2023, seul un engagement collectif en faveur d'un partage d'informations permettra d'assurer une réponse préventive et thérapeutique appropriée et rapide.

Robust T-Cell Responses in Anti-CD20-Treated Patients Following COVID-19 Vaccination: A Prospective Cohort Study.

BACKGROUND: Patients treated with anti-CD20 therapy are particularly at risk of developing severe coronavirus disease 2019 (COVID-19); however, little is known regarding COVID-19 vaccine effectiveness in this population. METHODS: This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n = 37), compared to immunocompetent individuals (n = 22). RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4 T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4 and CD8 T cells were polyfunctional but expressed more effector molecules in patients than in controls. During follow-up, 3 MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination. CONCLUSIONS: Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.

Risk of Reinfection After Seroconversion to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Population-based Propensity-score Matched Cohort Study.

BACKGROUND: Serological assays detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are being widely deployed in studies and clinical practice. However, the duration and effectiveness of the protection conferred by the immune response remains to be assessed in population-based samples. To estimate the incidence of newly acquired SARS-CoV-2 infections in seropositive individuals as compared to seronegative controls, we conducted a retrospective longitudinal matched study. METHODS: A seroprevalence survey including a representative sample of the population was conducted in Geneva, Switzerland, between April and June 2020, immediately after the first pandemic wave. Seropositive participants were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, body mass index (BMI), smoking status, and education level. Each individual was linked to a state-registry of SARS-CoV-2 infections. Our primary outcome was confirmed infections occurring from serological status assessment to the end of the second pandemic wave (January 2021). RESULTS: Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (standard deviation [SD] 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of whom 5 (1.0%) were classified as reinfections. In contrast, the infection rate was higher in seronegative individuals (15.5%, 154/996) during a similar follow-up period (mean 34.7 [SD 3.2] weeks), corresponding to a 94% (95% confidence interval [CI]: 86%- 98%, P < .001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositives. CONCLUSIONS: Seroconversion after SARS-CoV-2 infection confers protection against reinfection lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.

One-year persistent symptoms and functional impairment in SARS-CoV-2 positive and negative individuals.

BACKGROUND: Persistent symptoms of SARS-CoV-2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS-CoV-2, including lockdown, social, and economic factors. OBJECTIVE: The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS-CoV-2 compared to individuals tested negative. METHODS: From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS-CoV-2 at the Geneva University Hospitals were followed up 12 months after their test date. RESULTS: At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS-CoV-2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS-CoV-2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS-CoV-2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60-6.83) and functional impairment (aOR 3.54; 2.16-5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40-59 years, and in individuals with no past medical or psychiatric history. CONCLUSION: SARS-CoV-2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.

External Quality Assessment of SARS-CoV-2 Sequencing: an ESGMD-SSM Pilot Trial across 15 European Laboratories.

This first pilot trial on external quality assessment (EQA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequencing, initiated by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Genomic and Molecular Diagnostics (ESGMD) and the Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing. Ten samples with various viral loads were sent out to 15 clinical laboratories that had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centers were compared were the identification of (i) single nucleotide polymorphisms (SNPs) and indels, (ii) Pango lineages, and (iii) clusters between samples. The participating laboratories used a wide array of methods and analysis pipelines. Most were able to generate whole genomes for all samples. Genomes were sequenced to various depths (up to a 100-fold difference across centers). There was a very good consensus regarding the majority of reporting criteria, but there were a few discrepancies in lineage and cluster assignments. Additionally, there were inconsistencies in variant calling. The main reasons for discrepancies were missing data, bioinformatic choices, and interpretation of data. The pilot EQA was overall a success. It was able to show the high quality of participating laboratories and provide valuable feedback in cases where problems occurred, thereby improving the sequencing setup of laboratories. A larger follow-up EQA should, however, improve on defining the variables and format of the report. Additionally, contamination and/or minority variants should be a further aspect of assessment.

Autoantibodies against apolipoprotein A-1 after COVID-19 predict symptoms persistence.

BACKGROUND: SARS-CoV-2 infection triggers different auto-antibodies, including anti-apolipoprotein A-1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID-19 and the impact of AAA1 on the inflammatory response and symptoms persistence. METHODS: All serologies were assessed at one, three, six and twelve months in 193 hospital employees with COVID-19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient-reported COVID-19 symptoms persistence at 12 months. Interferon (IFN)-α and-γ production by AAA1-stimulated human monocyte-derived macrophages (HMDM) was assessed in vitro. RESULTS: AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID-19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti-SARS-COV2 serologies decreased, but remained significant. From the 3rd month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72-0.74; p < 0.001), independently of disease severity, age and gender (adjusted odds ratios 4.81-4.94; p = 0.02), while anti-SARS-CoV-2 serologies did not. AAA1 increased IFN-α production by HMDMs (p = 0.03), without affecting the IFN-γ response. CONCLUSION: COVID-19 induces a marked though transient AAA1 response, independently predicting one-year persistence of respiratory symptoms. By increasing IFN-α response, AAA1 may contribute to persistent symptoms. If and how AAA1 levels assessment could be of use for COVID-19 risk stratification remains to be determined.

Characterization of pathogen-inactivated COVID-19 convalescent plasma and responses in transfused patients.

BACKGROUND: Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics. STUDY DESIGN AND METHODS: In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients. RESULTS: Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients. DISCUSSION: PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.

Clinical sign and biomarker-based algorithm to identify bacterial pneumonia among outpatients with lower respiratory tract infection in Tanzania.

BACKGROUND: Inappropriate antibiotics use in lower respiratory tract infections (LRTI) is a major contributor to resistance. We aimed to design an algorithm based on clinical signs and host biomarkers to identify bacterial community-acquired pneumonia (CAP) among patients with LRTI. METHODS: Participants with LRTI were selected in a prospective cohort of febrile (≥ 38 °C) adults presenting to outpatient clinics in Dar es Salaam. Participants underwent chest X-ray, multiplex PCR for respiratory pathogens, and measurements of 13 biomarkers. We evaluated the predictive accuracy of clinical signs and biomarkers using logistic regression and classification and regression tree analysis. RESULTS: Of 110 patients with LRTI, 17 had bacterial CAP. Procalcitonin (PCT), interleukin-6 (IL-6) and soluble triggering receptor expressed by myeloid cells-1 (sTREM-1) showed an excellent predictive accuracy to identify bacterial CAP (AUROC 0.88, 95%CI 0.78-0.98; 0.84, 0.72-0.99; 0.83, 0.74-0.92, respectively). Combining respiratory rate with PCT or IL-6 significantly improved the model compared to respiratory rate alone (p = 0.006, p = 0.033, respectively). An algorithm with respiratory rate (≥ 32/min) and PCT (≥ 0.25 µg/L) had 94% sensitivity and 82% specificity. CONCLUSIONS: PCT, IL-6 and sTREM-1 had an excellent predictive accuracy in differentiating bacterial CAP from other LRTIs. An algorithm combining respiratory rate and PCT displayed even better performance in this sub-Sahara African setting.

Occupational risk of SARS-CoV-2 infection and reinfection during the second pandemic surge: a cohort study.

OBJECTIVES: This cohort study including essential workers, assessed the risk and incidence of SARS-CoV-2 infection during the second surge of COVID-19 according to baseline serostatus and occupational sector. METHODS: Essential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralised registry compiling SARS-CoV-2 infections. Primary outcome was the incidence of virologically confirmed infections from serological assessment (between May and September 2020) to 25 January 2021, according to baseline antibody status and stratified by three predefined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others). RESULTS: 10 457 essential workers were included (occupations requiring sustained physical proximity accounted for 3057 individuals, those involving regular brief contact, 3645 and 3755 workers were classified under 'Other essential occupations'). After a follow-up period of over 27 weeks, 5 (0.6%) seropositive and 830 (8.5%) seronegative individuals had a positive SARS-CoV-2 test, with an incidence rate of 0.2 (95% CI 0.1 to 0.6) and 3.2 (95% CI 2.9 to 3.4) cases per person-week, respectively. Incidences were similar across occupational groups. Seropositive essential workers had a 93% reduction in the hazard (HR of 0.07, 95% CI 0.03 to 0.17) of having a positive test during the follow-up with no significant between-occupational group difference. CONCLUSIONS: A 10-fold reduction in the hazard of being virologically tested positive was observed among anti-SARS-CoV-2 seropositive essential workers regardless of their sector of occupation, confirming the seroprotective effect of a previous SARS-CoV2 exposure at least 6 months after infection.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies, risk factors for infection and associated symptoms in Geneva, Switzerland: a population-based study.

Aims: To assess SARS-CoV-2 seroprevalence over the first epidemic wave in the canton of Geneva, Switzerland, as well as risk factors for infection and symptoms associated with IgG seropositivity. Methods: Between April and June 2020, former participants of a representative survey of the 20-74-year-old population of canton Geneva were invited to participate in the study, along with household members aged over 5 years. Blood samples were tested for anti-SARS-CoV-2 immunoglobulin G. Questionnaires were self-administered. We estimated seroprevalence with a Bayesian model accounting for test performance and sampling design. Results: We included 8344 participants, with an overall adjusted seroprevalence of 7.8% (95% credible interval 6.8-8.9). Seroprevalence was highest among 18-49 year-olds (9.5%), and lowest in 5-9-year-old children (4.3%) and individuals >65 years (4.7-5.4%). Odds of seropositivity were significantly reduced for female retirees and unemployed men compared to employed individuals, and smokers compared to non-smokers. We found no significant association between occupation, level of education, neighborhood income and the risk of being seropositive. The symptom most strongly associated with seropositivity was anosmia/dysgeusia. Conclusions: Anti-SARS-CoV-2 population seroprevalence remained low after the first wave in Geneva. Socioeconomic factors were not associated with seropositivity in this sample. The elderly, young children and smokers were less frequently seropositive, although it is not clear how biology and behaviours shape these differences.

Frequency and causes of antifungal treatment changes in allogeneic haematopoïetic cell transplant recipients with invasive mould infections.

BACKGROUND: Antifungal treatment duration and changes for invasive mould infections (IMI) have been poorly described. METHODS: We performed a 10-year cohort study of adult (≥18-year-old) allogeneic haematopoietic cell transplant recipients with proven/probable IMI to describe the duration and changes of antifungal treatment. All-cause-12-week mortality was described. RESULTS: Sixty-one patients with 66 IMI were identified. Overall treatment duration was 157 days (IQR: 14-675) and 213 (IQR: 90-675) days for patients still alive by Day 84 post-IMI diagnosis. There was at least one treatment change in 57/66 (86.4%) cases: median 2, (IQR: 0-6, range:0-8). There were 179 antifungal treatment changes due to 193 reasons: clinical efficacy (104/193, 53.9%), toxicity (55/193, 28.5%), toxicity or drug interactions resolution (15/193, 7.8%) and logistical reasons (11/193, 5.7%) and 15/193 (7.8%) changes due to unknown reasons. Clinical efficacy reasons included lack of improvement (34/104, 32.7%), targeted treatment (30/104, 28.8%), subtherapeutic drug levels (14/104, 13.5%) and other (26/104, 25%). Toxicity reasons included hepatotoxicity, nephrotoxicity, drug interactions, neurotoxicity and other in 24 (43.6%), 12 (21.8%), 12 (21.8%), 4 (7.4%) and 3 (5.5%) cases respectively. All-cause 12-week mortality was 31% (19/61), higher in patients whose antifungal treatment (logrank 0.04) or appropriate antifungal treatment (logrank 0.01) was started >7 days post-IMI diagnosis. All-cause 1-year mortality was higher in patients with ≥2 changes of treatment during the first 6 weeks post-IMI diagnosis (logrank 0.008) with an OR: 4.00 (p = .04). CONCLUSIONS: Patients with IMI require long treatment courses with multiple changes for variable reasons and potential effects on clinical outcomes, demonstrating the need more effective and safer treatment options. Early initiation of appropriate antifungal treatment is associated with improved outcomes.

Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients.

Viral primary infections and reactivations are common complications in patients after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and are associated with high morbidity and mortality. Among these patients, viral infections are frequently associated with viremia. Beyond the usual well-known viruses that are part of the routine clinical management of transplant recipients, numerous other viral signatures or genomes can be identified in the blood of these patients. The identification of novel viral species and variants by metagenomic next-generation sequencing has opened up a new field of investigation and new paradigms. Thus, there is a need to thoroughly describe the state of knowledge in this field with a review of all viral infections that should be scrutinized in high-risk populations. Here, we review the eukaryotic DNA and RNA viruses identified in blood, plasma, or serum samples of pediatric and adult SOT/HSCT recipients and the prevalence of their detection, with a particular focus on recently identified viruses and those for which their potential association with disease remains to be investigated, such as members of the Polyomaviridae, Anelloviridae, Flaviviridae, and Astroviridae families. Current knowledge of the clinical significance of these viral infections with associated viremia among transplant recipients is also discussed. To ensure a comprehensive description in these two populations, individuals described as healthy (mostly blood donors) are considered for comparative purposes. The list of viruses that should be on the clinicians' radar is certainly incomplete and will expand, but the challenge is to identify those of possible clinical significance.

[An infectious diseases ward dedicated to elderly patients: why and how?] / Unité d'infectiologie gériatrique : pourquoi et comment ?

The management of infections in the elderly requires medical and nursing expertise with a standardized global geriatric evaluation. We present here an original and pioneering unit in Switzerland, dedicated to polymorbid and complex elderly patients hospitalized for an acute infection and who will benefit from joint management by an interdisciplinary team including a geriatrician, an infectious diseases specialist and a pharmacogeriatrician. The Hôpital des Trois-Chêne, which has geriatric emergencies, intermediate care beds, SOMADEM (somatic dementia) and UGIMP (medico-psychiatric) programs adapted to this population, seems to be the ideal place to host this unit. The teams will benefit from theoretical and practical training associated with field coaching.

La prise en charge des infections de la personne âgée nécessite une expertise médico-soignante avec une évaluation gériatrique globale standardisée. Nous présentons ici une unité originale et pionnière en Suisse, dédiée aux patients âgés polymorbides et complexes hospitalisés pour infection aiguë. Ils bénéficieront d'une prise en charge conjointe par une équipe interdisciplinaire comprenant entre autres le gériatre, l'infectiologue et le pharmacogériatre. L'hôpital des Trois-Chêne, qui possède des urgences gériatriques, des lits de soins intermédiaires, les programmes SOMADEM (somatique démence) et UGIMP (médico-psychiatrique) adaptés à cette population, semble le lieu idéal pour accueillir cette unité. Les équipes bénéficieront d'une formation théorique et pratique associée à du coaching de terrain.