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Nonenveloped viruses enter target cells by endocytosis. Prisoner into intracellular vesicles, they use different mechanisms to allow liberation of their genome and its transport in replication and expression sites. The parvoviruses are small nonenveloped single-stranded DNA viruses that should enter the cell nucleus for replication. One of their capsid proteins carries a phospholipase A2 (PLA2) enzymatic activity that is necessary for infectiosity. The viral PLA2 leads to membrane lysis allowing the liberation of the nucleocapsid from vesicles and its transport to the nucleus. The PLA2 could be involved in immunopathologic phenomenon observed during B19 infection in humans.

Patients with chronic obstructive pulmonary disease (COPD) exhibit frequent acute exacerbations (AE). The objectives of this study were first to evaluate the prevalence of pathogens associated to these episodes by combining conventional bacteriology and multiplex viral and bacterial PCR assays in sputum specimens, and second to determine whether C-reactive protein (CRP) value and clinical outcome could be influenced by the type of microbial agent(s) recovered from these samples. A cohort of 84 Tunisian patients hospitalized at the emergency room for AECOPD was investigated prospectively for the semi-quantitative detection of bacteria by conventional culture (the threshold of positivity was of 10

Three autochthonous cases of tick-borne encephalitis (TBE) acquired in rural areas of France where Lyme borreliosis, but not TBE, is endemic highlight the emergence of TBE in new areas. For patients with neurologic involvement who have been in regions where Ixodes ticks circulate, clinicians should test for TBE virus and other tickborne viruses.

Objectives This study aimed to evaluate the immunochromatographic coronavirus disease 2019 (COVID-19) speed antigen test (BioSpeedia, France) as an antigen point-of-care test (AgPOCT) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the paediatric emergency department of the University Hospital of Saint-Etienne in France. Methods Between 15 January and 28 May, 2021, children presenting with respiratory symptoms compatible with COVID-19 infection (symptomatic group) or those requiring hospitalization for any reason (asymptomatic group) were included prospectively and received a nasopharyngeal aspiration to carry out both AgPOCT and quantitative reverse transcription (RT) PCR (RT-qPCR) tests, with the latter being used as the reference standard, for the diagnosis of SARS-CoV-2 infection. Results Among the 1009 enrolled children, we obtained a result from both techniques for 990: 33 (3.3%) tested positive with AgPOCT and 46 (4.6%) with RT-qPCR. The overall sensitivity and specificity of the AgPOCT were 69.6% (95% confidence interval (CI), 54.3–82.3) and 99.9% (95% CI, 99.4–100), respectively, compared with the RT-qPCR. Sensitivity increased to 82.9% (95% CI, 66.4–93.4) in symptomatic children. The mean cycle threshold value was significantly lower in positive samples for AgPOCT than in negative samples in the overall population and in both the symptomatic and asymptomatic groups. Discussion The use of the COVID-19 speed antigen test at the bedside in the emergency department has satisfactory performance for diagnosing SARS-CoV-2 infection in symptomatic children.

This article reports the observed rate of infection with severe acute respiratory syndrome coronavirus-2 in healthcare workers (HCWs) who worked on wards dedicated to care of patients with coronavirus disease 2019 (COVID-19) compared with HCWs who worked on non-COVID-19 wards. The infection rate was significantly higher among HCWs who worked on non-COVID-19 wards (odds ratio 2.3, P=0.005), illustrating the need to strengthen social distancing measures and training.

Background The risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission through corneal graft is an ongoing debate and leads to strict restrictions in corneas procurement, leading to a major decrease in eye banking activity. The aims of this study are to specifically assess the capacity of human cornea to be infected by SARS-CoV-2 and promote its replication ex vivo, and to evaluate the real-life risk of corneal contamination by detecting SARS-CoV-2 RNA in corneas retrieved in donors diagnosed with Coronavirus Disease 2019 (COVID-19) and nonaffected donors. Methods and findings To assess the capacity of human cornea to be infected by SARS-CoV-2, the expression pattern of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE-2) and activators TMPRSS2 and Cathepsins B and L in ocular surface tissues from nonaffected donors was explored by immunohistochemistry (n = 10 corneas, 78 ± 11 years, 40% female) and qPCR (n = 5 corneas, 80 ± 12 years, 40% female). Additionally, 5 freshly excised corneas (80 ± 12 years, 40% female) were infected ex vivo with highly concentrated SARS-CoV-2 solution (106 median tissue culture infectious dose (TCID50)/mL). Viral RNA was extracted from tissues and culture media and quantified by reverse transcription quantitative PCR (RT-qPCR) (viral RNA copies) 30 minutes (H0) and 24 hours (H24) after infection. To assess the risk of corneal contamination by SARS-CoV-2, viral RNA was tested by RT-qPCR (Ct value) in both corneas and organ culture media from 14 donors diagnosed with COVID-19 (74 ± 10 years, 29% female) and 26 healthy donors (79 ± 13 years, 57% female), and in organ culture media only from 133 consecutive nonaffected donors from 2 eye banks (73 ± 13 years, 29% female). The expression of receptor and activators was variable among samples at both protein and mRNA level. Based on immunohistochemistry findings, ACE-2 was localized mainly in the most superficial epithelial cells of peripheral cornea, limbus, and conjunctiva, whereas TMPRSS2 was mostly expressed in all layers of bulbar conjunctiva. A significant increase in total and positive strands of IP4 RNA sequence (RdRp viral gene) was observed from 30 minutes to 24 hours postinfection in central cornea (1.1 × 108 [95% CI: 6.4 × 107 to 2.4 × 108] to 3.0 × 109 [1.4 × 109 to 5.3 × 109], p = 0.0039 and 2.2 × 107 [1.4 × 107 to 3.6 × 107] to 5.1 × 107 [2.9 × 107 to 7.5 × 107], p = 0.0117, respectively) and in corneoscleral rim (4.5 × 109 [2.7 × 109 to 9.6 × 109] to 3.9 × 1010 [2.6 × 1010 to 4.4 × 1010], p = 0.0039 and 3.1 × 108 [1.2 × 108 to 5.3 × 108] to 7.8 × 108 [3.9 × 108 to 9.9 × 108], p = 0.0391, respectively). Viral RNA copies in ex vivo corneas were highly variable from one donor to another. Finally, viral RNA was detected in 3 out of 28 corneas (11%) from donors diagnosed with COVID-19. All samples from the 159 nonaffected donors were negative for SARS-CoV-2 RNA. The main limitation of this study relates to the limited sample size, due to limited access to donors diagnosed with COVID-19 and concomitant decrease in the procurement corneas from nonaffected donors. Conclusions In this study, we observed the expression of SARS-CoV-2 receptors and activators at the human ocular surface and a variable increase in viral RNA copies 24 hours after experimental infection of freshly excised human corneas. We also found viral RNA only in a very limited percentage of donors with positive nasopharyngeal PCR. The low rate of positivity in donors diagnosed with COVID-19 calls into question the utility of donor selection algorithms. Trial registration Agence de la Biomédecine, PFS-20-011 https://www.agence-biomedecine.fr/.

BackgroundSARS-CoV-2 mutations appeared recently and can lead to conformational changes in the spike protein and probably induce modifications in antigenicity. In this study, we wanted to assess the neutralizing capacity of antibodies to prevent cell infection, using a live virus neutralisation test.MethodsSera samples were collected from different populations: two-dose vaccinated COVID-19-naïve healthcare workers (HCWs; Pfizer-BioNTech BNT161b2), 6-months post mild COVID-19 HCWs, and critical COVID-19 patients. We tested various clades such as 19A (initial one), 20B (B.1.1.241 lineage), 20I/501Y.V1 (B.1.1.7 lineage), and 20H/501Y.V2 (B.1.351 lineage).ResultsNo significant difference was observed between the 20B and 19A isolates for HCWs with mild COVID-19 and critical patients. However, a significant decrease in neutralisation ability was found for 20I/501Y.V1 in comparison with 19A isolate for critical patients and HCWs 6-months post infection. Concerning 20H/501Y.V2, all populations had a significant reduction in neutralising antibody titres in comparison with the 19A isolate. Interestingly, a significant difference in neutralisation capacity was observed for vaccinated HCWs between the two variants whereas it was not significant for the convalescent groups.ConclusionNeutralisation capacity was slightly reduced for critical patients and HCWs 6-months post infection. No neutralisation escape could be feared concerning the two variants of concern in both populations. The reduced neutralising response observed towards the 20H/501Y.V2 in comparison with the 19A and 20I/501Y.V1 isolates in fully immunized subjects with the BNT162b2 vaccine is a striking finding of the study.

Objectives This prospective study performed in the paediatric emergency department of the University Hospital of Saint-Etienne aimed to measure the impact of the 24/7 bedside use of the Veritor™ System (Becton Dickinson) on the reduction of supplementary investigations, hospital stay and antimicrobial use. Methods Influenza virus A and B antigens were detected with a rapid influenza digital immunoassay (DIA) on nasopharyngeal aspirates (NPAs) sampled from the children consulting at the paediatric emergency department between January and March 2016 for influenza-like illness. The same NPA was tested by immunofluorescence and/or molecular routine assays. Before performing the DIA, the clinician filled in a questionnaire listing the tests that he/she would have prescribed in the absence of the rapid testing. The prescription of complementary investigations, antimicrobial treatments and hospital stay were also compared to those of the 3 previous years. Results A total of 514 children with flu-like symptoms were included. The use of the DIA at bedside decreased the prescription of blood puncture by 47.9% (21.2% to 6.6%), of chest X-rays by 69.0% (33.3% to 10.3%), of lumbar puncture by 77.8% (7.0% to 1.6%), of urine culture by 79.2% (23.3% to 4.9%), of antibiotic treatments by 70.1% (16.9% to 5.1%), and of hospital stay by 25.0% (27.2% to 20.4%), resulting in a reduction of medical costs estimated to more than €69 000 in a season. Conclusions In addition to delivering a rapid aetiological diagnosis, this strategy saves medical costs and favours an antimicrobial stewardship strategy. However, further prospective studies are needed to confirm our findings.

The in vitro propagation of human rhinoviruses (RVs) is difficult because only few continuous human cell lines are permissive to these agents. We propose an innovative model of epithelial cell infection using a non-transformed continuous keratinocyte line from human origin (HaCaT cells). After infection with RV-A13, RV-A16 or RV-A19, HaCaT cells produced infectious particles without showing any observable cytopathic effect and overexpressed ICAM-1 (intercellular adhesion molecule 1), the major entry receptor of RVs. Furthermore, the treatment of HaCaT cells with 10 µM clarithromycin reduced the viral titer by 93% and 60% during the first and second days following viral infection, respectively, probably by down-regulating ICAM-1 expression. This original model of epithelial cell infection by RV could be useful to study chronic viral infection and bacterium-virus interactions at the cell level. These results also suggest that clarithromycin may be evaluated for treating in vivo infections associating RV to a susceptible bacterium.

This study assessed the diagnostic performance of the new coronavirus disease 2019 (COVID-19) SEROSpeed IgM/IgG Rapid Test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders)., This study assessed the diagnostic performance of the new COVID19SEROSpeed IgM/IgG rapid test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders). The clinical sensitivity was evaluated on 710 sera from 564 patients whose SARS-CoV-2 infection was confirmed by quantitative reverse transcription-PCR (qRT-PCR) and whose antibody response was compared to that measured by five other commercial tests. The kinetics of the antibody response were also analyzed in seven symptomatic patients. The specificity of the test (BioS) on prepandemic specimens was 98.1% (95% confidence interval [CI], 96.2% to 99.4%). When tested on the 710 pandemic specimens, BioS showed an overall clinical sensitivity of 86.0% (95% CI, 0.83 to 0.89), with good concordance with the Euroimmun assay (overall concordance of 0.91; Cohen’s kappa coefficient of 0.62). Due in part to simultaneous detection of IgM and IgG for both S1 and N proteins, BioS exhibited the highest positive percent agreement at ≥11 days post-symptom onset (PSO). In conclusion, the BioS IgM/IgG rapid test was highly specific and demonstrated a higher positive percentage of agreement than all the enzyme-linked immunosorbent assay/chemiluminescence immunoassay (ELISA/CLIA) commercial tests considered in this study. Moreover, by detecting the presence of antibodies prior to 11 days PSO in 78.2% of the patients, the BioS test increased the efficiency of the diagnosis of SARS-CoV-2 infection in the early stages of the disease.

Graphical abstract, Context Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that emerged late in 2019 is the etiologic agent of coronavirus disease 2019 (Covid-19). There is an urgent need to develop curative and preventive therapeutics to limit the current pandemic and to prevent the re-emergence of Covid-19. This study aimed to assess the in vitro activity of copper gluconate against SARS-CoV-2. Methods Vero E6 cells were cultured with or without copper gluconate 18−24 hours before infection. Cells were infected with a recombinant GFP expressing SARS-CoV-2. Cells were infected with a recombinant GFP expressing SARS-CoV-2. Infected cells were incubated in fresh medium containing varying concentration of copper gluconate (supplemented with bovine serum albumin or not) for an additional 48 -h period. The infection level was measured by the confocal microscopy-based high content screening method. The cell viability in presence of copper gluconate was assessed by XTT and propidium iodide assays. Results The viability of Vero E6 cells exposed to copper gluconate up to 200 μM was found to be similar to that of unexposed cells, but it dropped below 70 % with 400 μM of this agent after 72 h of continuous exposure. The infection rate was 23.8 %, 18.9 %, 20.6 %, 6.9 %, 5.3 % and 5.2 % in cells treated prior infection with 0, 2, 10, 25, 50 and 100 μM of copper gluconate respectively. As compared to untreated cells, the number of infected cells was reduced by 71 %, 77 %, and 78 % with 25, 50, and 100 μM of copper gluconate respectively (p < 0.05). In cells treated only post-infection, the rate of infection dropped by 73 % with 100 μM of copper gluconate (p < 0.05). However, the antiviral activity of copper gluconate was abolished by the addition of bovine serum albumin. Conclusion Copper gluconate was found to mitigate SARS-CoV-2 infection in Vero E6 cells but this effect was abolished by albumin, which suggests that copper will not retain its activity in serum. Furthers studies are needed to investigate whether copper gluconate could be of benefit in mucosal administration such as mouthwash, nasal spray or aerosols.

BACKGROUND Cardiorespiratory decompensation (CRD) visits have a profound effect on adult emergency departments (EDs). Respiratory pathogens like respiratory syncytial virus (RSV) and influenza virus are common reasons for increased activity in pediatric EDs and are associated with CRD in the adult population. Given the seasonal aspects of such challenging pathology, it would be advantageous to predict their variations. OBJECTIVE The goal of this study was to evaluate the increased burden of CRD in adult EDs during flu and bronchiolitis outbreaks in the pediatric population. METHODS An ecological study was conducted, based on admissions to the adult ED of the Centre Hospitalier Universitaire (CHU) of Grenoble and Saint Etienne from June 29, 2015 to March 22, 2020. The outbreak periods for bronchiolitis and flu in the pediatric population were defined with a decision-making support tool, PREDAFLU, used in the pediatric ED. A Kruskal-Wallis variance analysis and a Spearman monotone dependency were performed in order to study the relationship between the number of adult ED admissions for the International Classification of Diseases (ICD)-10 codes related to cardiorespiratory diagnoses and the presence of an epidemic outbreak as defined with PREDAFLU. RESULTS The increase in visits to the adult ED for CRD and the bronchiolitis and flu outbreaks had a similar distribution pattern (CHU Saint Etienne: χ23=102.7, Pχ23=126.67, Pρ=0.64; CHU Grenoble: Spearman ρ=0.71). The increase in ED occupancy for these pathologies was also significantly related to the pediatric respiratory infection outbreaks. These 2 criteria gave an idea of the increased workload in the ED due to CRD during the bronchiolitis and flu outbreaks in the pediatric population. CONCLUSIONS This study established that CRD visits and bed occupancy for adult EDs were significantly increased during bronchiolitis and pediatric influenza outbreaks. Therefore, a prediction tool for these outbreaks such as PREDAFLU can be used to provide early warnings of increased activity in adult EDs for CRD visits.

Cytomegalovirus (CMV) infects approximately 50 % of adults in France and persists lifelong as a latent agent in different organs, including the gut. A close relationship is observed between inflammation that favors viral expression, and viral replication that modulates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBD), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation in link with Th2 cytokines, together with immunomodulatory drugs used for controlling flares-up, favors viral reactivation within the gut, which increases mucosal inflammation ; it results in an important risk of impairing corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in case of CMV colitis), precipitating the need for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during IBD and underlines the interest of using ganciclovir for treating flares-up associated to CMV colitis in UC patients.

The discovery of the human parvovirus B19 was done by Yvonne Cossart in 1975. In addition to fifth disease and aplastic crisis numerous clinical manifestations have been associated with B19 infections. Routine virological diagnosis is made by the detection of specific IgM and sometimes by the detection of viral DNA. Some clinicians are perplexed by the persistence of B19 DNAemia after acute infections. In this point of view we try to discuss this problematic.

Background Oseltamivir shows effectiveness in reducing influenza-related symptoms, morbidity and mortality. Its prescription remains suboptimal. Objectives We aim to describe oseltamivir prescription in confirmed cases of influenza and to identify associated factors. Methods A prospective monocentric observational study was conducted between 1 December 2018 and 30 April 2019. All patients with a virologically confirmed influenza diagnosis were included. Factors associated with oseltamivir prescription were studied. Results Influenza was confirmed in 755 patients (483 children and 272 adults), of which 188 (25.1%) were hospitalized and 86 (11.4%) had signs of severity. Oseltamivir was prescribed for 452 patients (59.9%), more frequently in children than in adults [329/483 (68.1%) versus 123/272 (45.2%), P Conclusions Oseltamivir should be administered as early as possible, preferably within 24–48 h after illness onset, for the best benefits. It is, however, very important to promote the use of neuraminidase inhibitor (‘NAI’) treatment beyond 48 h in some specific patient populations.

Highlights • In case of virus emergence, laboratory-developed assays (LDA) should be urgently assessed. • Recommended open one-step RT-qPCR reagents are rapidly on tension in case of pandemic. • Five other reagents were shown to be used for SARS-CoV-2 RNA detection by LDA. • This study can help laboratories to assess LDA for detecting emerging RNA viruses., Background Facing the emergence of a new RNA virus, clinical laboratories are often helpless in the face of a shortage of reagents recommended by Reference Centres. Objectives To compare five open one step RT-qPCR reagents to the SuperScript™ III Platinum™ One-Step qRT-PCR kit (Invitrogen) considered as the reference one in France at the beginning of the pandemic for detection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in respiratory specimens by using laboratory-developed assay targeting the viral RNA dependant RNA polymerase (RdRp) gene. Study design A total of 51 NUCLISENS easyMAG extracts from respiratory specimens was tested on ABI 7500 thermocycler with TaqMan Fast Virus 1-Step Master Mix (Applied Biosystems), Luna® Universal Probe One-Step RT-qPCR Kit (New England Biolabs), GoTaq® Probe 1- Step RT-qPCR System (Promega), LightCycler® Multiplex RNA Virus Master (Roche) and One-step PrimeScript RT-PCR kit (Takara). The CT values obtained using the 5 challenged reagents were compared to those obtained using the reference assay. Results The percentages of concordance were all above 95 %. When comparing the CT values of the 48 extracts exhibiting CT values < 35 obtained with the reference reagent, the results were similar between the reagents although the differences of CT values were quite dispersed. Conclusions All five reagents can be considered as alternative reagents to the reference for detecting SARS−COV-2 RNA.

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection from re-infection and, thus, for public health policy and for vaccine development against the COVID-19. Here, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum specimens from a cohort of 140 SARS-CoV-2 qPCR-confirmed patients, including patient with mild symptoms but also more severe form including those that require intensive care. We show that nAb titers were strongly correlated with disease severity and with anti-Spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers, whereas patients with milder disease symptoms displayed heterogenous nAb titers and asymptomatic or exclusive outpatient care patients had no or poor nAb levels. We found that the nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery, as compared to individuals infected with alternative coronaviruses. We show the absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAb against SARS-CoV-2 infection. Finally, we found that the D614G mutation in the Spike protein, which has recently been identified as the major variant now found in Europe, does not allow neutralization escape. Altogether, our results contribute to the understanding of the immune correlate of SARS-CoV-2 induced disease and claim for a rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2.

Objectives: Our aim is to compare the course of the disease between healthcare workers (HCWs) and non-HCWs suffering from covid-19 and eligible for outpatient management. Methods: Single-center prospective cohort of outpatients with covid-19, diagnosed between the 10th March and the 2nd April, 2020 with a daily collection of symptoms by an on-line auto-questionnaire. Results: A total of 186 patients were included (median age, 41 years [interquartile range, 19-78 years]; 74.2% female), of whom 132 (71 %) were HCWs. The median follow-up after symptom onset was 14 (min 4 - max 24) days. HCWs were significantly younger than non HCWs (median age 40.3 years vs. 47.2 years [p

International audience; Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.

Background Influenza is an important cause of viral hospital-acquired infection involving patients, healthcare workers (HCW), and visitors. The frequency of asymptomatic influenza among HCW with possible subsequent transmission is poorly described. The objective is to determine the cumulative incidence of asymptomatic, paucisymptomatic, and symptomatic influenza among HCW. Method A multicenter prospective cohort study was done in 5 French university hospitals, including 289 HCW during the 2016–2017 influenza season. HCW had 3 physical examinations (time [T] 0, before epidemic onset; T.1, before epidemic peak; T.2, T.3, after epidemic peak). A blood sample was taken each time for influenza serology and a nasal swab was collected at T1 and T2 for influenza detection by polymerase chain reaction (PCR). Positive influenza was defined as either a positive influenza PCR, and/or virus-specific seroconversion against influenza A, the only circulating virus, with no vaccination record during follow-up. Symptoms were self-reported daily between T1 and T2. Cumulative incidence of influenza was stratified by clinical presentation per 100 HCW. Results Of the 289 HCW included, 278 (96%) completed the entire follow-up. Overall, 62 HCW had evidence of influenza of whom 46.8% were asymptomatic, 41.9% were paucisymptomatic, and 11.3% were symptomatic. Cumulative influenza incidence was 22.3% (95% confidence interval [CI]: 17.4%–27.2%). Cumulative incidence of asymptomatic influenza was 5.8% (95% CI: 3.3%–9.2%), 13.7% (95% CI: 9.9%–18.2%) for paucisymptomatic influenza, and 2.9% (95% CI: 1.3%–5.5%) for symptomatic influenza. Conclusions Asymptomatic and paucisymptomatic influenza were frequent among HCW, representing 47% and 42% of the influenza burden, respectively. These findings highlight the importance of systematic implementation of infection control measures among HCW regardless of respiratory symptoms from preventing nosocomial transmission of influenza. Clinical Trials Registration NCT02868658.

BackgroundHerpetic keratitis (HK) models using whole human corneas are essential for studying virus-host relationships, because of high species specificity and the role of interactions between corneal cell populations that cell culture cannot reproduce. Nevertheless, the two current corneal storage methods (hypothermia and organ culture (OC)) do not preserve corneas in good physiological condition, as they are characterized by epithelial abrasion, stromal oedema, and excessive endothelial mortality.MethodsTo rehabilitate human corneas intended for scientific use, we used an active storage machine (ASM) that restores two physiological parameters that are essential for corneal homeostasis: intraocular pressure and storage medium renewal (21mmHg and 2.6 μL/min, respectively). ASM storage regenerates a normal multilayer epithelium in 2 weeks. We infected six pairs of corneas unsuitable for graft by inoculating the epithelium with herpes simplex virus type 1 (HSV-1), and compared each ASM-stored cornea with the other cornea stored in the same medium using the conventional OC method.ResultsOnly corneas in the ASM developed a dendritic (n = 3) or geographic (n = 2) epithelial ulcer reproducing typical HSV-1-induced clinical lesions. Corneas in OC showed only extensive desquamations. None of the uninfected controls showed epithelial damage. Histology, immunohistochemistry, transmission electron microscopy and polymerase chain reaction on corneal tissue confirmed infection in all cases (excluding negative controls).ConclusionsThe ASM provides an innovative ex vivo model of HK in whole human cornea that reproduces typical epithelial lesions.

Little is known about the dynamic of HIV-1 shedding and resistance profiles in the female genital reservoir after antiretroviral therapy (ART) initiation in resource-limited countries (RLCs), which is critical for evaluating the residual sexual HIV-1 transmission risk. The present study aimed to evaluate the efficacy of 1 year duration ART at blood and genital levels in females newly diagnosed for HIV-1 from three centers in Bamako, Mali. Seventy-eight consenting females were enrolled at the time of their HIV-1 infection diagnosis. HIV-1 RNA loads (Abbott Real-Time HIV-1 assay) were tested in blood and cervicovaginal fluids (CVF) before and 12 months after ART initiation. Primary and acquired resistances to ART were evaluated by ViroseqTM HIV-1 genotyping assay. The vaginal microbiota was analyzed using IonTorrentTM NGS technology (Thermo Fisher Scientific). Proportions of primary drug resistance mutations in blood and CVF were 13.4% and 25%, respectively. Discrepant profiles were observed in 25% of paired blood/CVF samples. The acquired resistance rate was 3.1% in blood. At month 12, undetectable HIV-1 RNA load was reached in 84.6% and 75% of blood and CVF samples, respectively. A vaginal dysbiosis was associated with HIV RNA shedding. Our findings emphasize the need of reinforcing education to improve retention in care system, as well as the necessity of regular virological monitoring before and during ART and of implementing vaginal dysbiosis diagnosis and treatment in RLCs.