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Background: Periodontitis (PDT) has gained attention in the literature with the increase in life expectancy of people living with HIV on combined antiretroviral therapy (cART). Thus, the search for inflammatory biomarkers could be useful to understand the pathophysiology of chronic oral diseases in the cART era. Objective: The aim of this study was to evaluate the impact of non-surgical periodontal therapy (NSPT) on clinical parameters of PDT, Candida spp. count and expression of LF and HST in saliva and CGF of HIV-infected patients. Methods: Bleeding index (BI), probing depth (PD), clinical attachment level (CAL), colony-forming units (CFUs) of Candida spp, and lactoferrin (LF) and histatin (HST) levels were measured in saliva and GCF of both groups at three different times: baseline (before treatment), and 30 and 90 days after the NSPT. Clinical, mycological and immunoenzymatic analyses were also performed. Results: Twenty-two HIV-infected patients and 25 non-HIV-infected patients with PDT participated in the study. NSPT was effective in improving periodontal clinical parameters, including ≤ 4 sites with PD ≤ 5mm and BI ≤ 10%. No significant change in oral Candida spp. count occurred neither between the two groups nor during the time after the periodontal treatment. And the salivary and GCF levels of LF and HST seems not to be influenced by the NSPT. By contrast, except for salivary LF, HST and LF were shown to exhibit significantly higher levels in HIV-infected than in non-HIV-infected patients. Conclusions: NSPT was effective in improving periodontal disease parameters in HIV-infected patients, but do not affect lactoferrin and histatin-5 expression in saliva and ginvival crevicular fluid of HIV-infected patients.

Omicron variant is circulating in the presence of a globally acquired immunity unlike the ancestral SARS-CoV-2 isolate. Herein, we investigated the normalized viral load dynamics and viral culture status in 44 fully vaccinated healthcare workers (HCWs) infected with the Omicron BA.1 variant. Viral load dynamics of 38 unvaccinated HCWs infected with the 20A variant during the first pandemic wave was also studied. We then explored the impact of Omicron infection on pre-existing immunity assessing anti-RBD IgG levels, neutralizing antibody titres against 19A, Delta and Omicron isolates, as well as IFN-γ release following cell stimulation with SARS-CoV-2 peptides. We reported that two weeks after diagnosis a greater proportion of HCWs infected with 20A (78.9%, 15/19) than with Omicron BA.1 (44.7%, 17/38; p = 0.02) were still positive by RT-qPCR. We found that Omicron breakthrough infections led to an overall enhancement of vaccine-induced humoral and cellular immunity as soon as a median [interquartile range] of 8 [7-9] days post symptom onset. Among samples with similar high viral loads, non-culturable samples exhibited higher neutralizing antibody titres and anti-RBD IgG levels than culturable samples. Additionally, Omicron infection led to an enhancement of antibodies neutralization capacity against other SARS-CoV-2 isolates. Taken together, the results suggest that Omicron BA.1 vaccine breakthrough infection is associated with a faster viral clearance than that of the ancestral SARS-CoV-2, in addition this new variant leads to a rapid enhancement of the humoral response against multiple SARS-CoV-2 variants, and of the cellular response.

Reliable immunoassays are essential to early predict and monitor vaccine efficacy against SARS-CoV-2. The performance of an Interferon Gamma Release Assay (IGRA, QuantiFERON® SARS-CoV-2), and a current anti-spike serological test, compared to a plaque reduction neutralization test (PRNT) taken as gold standard were compared. Eighty vaccinated individuals, whose 16% had a previous history of COVID-19, were included in a longitudinal prospective study and sampled before and two to four weeks after each dose of vaccine. In non-infected patients, 2 doses were required for obtaining both positive IGRA and PRNT assays, while serology was positive after one dose. Each dose of vaccine significantly increased the humoral and cellular response. By contrast, convalescent subjects needed a single dose of vaccine to be positive on all 3 tests. Both IGRA and current serology assay were found predictive of a positive titer of neutralizing antibodies that is correlated with vaccine protection. Patients over 65 or 80 years old had a significantly reduced response. The response tended to be better with the heterologous scheme (vs. homologous) and with the mRNA-1273 vaccine (vs. BNT162b2) in the homologous group, in patients under 55 and under 65 years old, respectively. Finally, decrease intensity or absence of IGRA response and to a less extent of anti-spike serology were also correlated to reinfection which has occurred during the follow up. In conclusion, both IGRA and current anti-spike serology assays could be used at defined thresholds to monitor the vaccine response against SARS-CoV-2 and to simply identify non-responding individuals after a complete vaccination scheme. Two available specific tests (IGRA and anti-spike antibodies) could early assess the vaccine-induced immunity against SARS-CoV-2 at the individual scale, to potentially adapt the vaccination scheme in non-responder patients.

Background:Exposure to infected healthcare workers (HCWs) is a source of hospital-acquired (HA) influenza. We estimated the risk of HA influenza for hospitalized patients by rate of influenza vaccine coverage (IVC) of HCWs.Methods:A case–case negative control study nested in a prospective cohort was conducted in 2 French university hospitals during 2 influenza seasons. Each inpatient with influenza-like illness (ILI) provided a nasal swab sample that was systematically analyzed for influenza virus by polymerase chain reaction (PCR) testing. An HA influenza case was a patient with a virological confirmation of influenza with onset of symptoms ≥72 hours after admission to the ward. The IVC rate of HCWs in each participating ward was calculated from the data provided by the occupational health departments. A mixed-effect logistic regression was performed with adjustments on patient sex, age, the presence of a potential source of influenza on the ward in the 5 days prior to the start of the ILI, type of ward and influenza season.Results:The overall HA influenza attack rate was 1.9 per 1,000 hospitalized patients. In total, 24 confirmed HA influenza cases and 141 controls were included. The crude odds ratio (OR) of HA influenza decreased from 0.52 (95% confidence interval [CI], 0.21–1.29) to 0.14 (95% CI, 0.03–0.63) when the IVC of HCWs increased from 20% to 40%. After adjustment, IVC ≥40% was associated with a risk reduction of HA influenza (aOR, 0.07; 95% CI, 0.01–0.78).Conclusions:Considering a limited sample size, influenza vaccination of HCWs is highly suggestive of HA flu prevention among hospitalized patients.Trial Registration: clinicaltrials.gov identifier: NCT02198638.

Covid-19 has spurred a renewed interest at decontamination techniques for air, objects and surfaces. Beginning 2020, a lot of effort was done in urgency to permit the reuse of UC-V for inactivating SARS-CoV-2. However, those studies diverged widely on the dose necessary to reach this goal; until today, the real value of the sensitivity of the virus to a 254-nm illumination is not known precisely. In this study, decontamination was performed in an original UV-C large decontamination chamber (UVCab, ON-LIGHT, France) delivering an omnidirectional irradiation with an average dose of 50 mJ/cm2 in 60 sec. Viral inactivation was checked by both cell culture and PCR test. SARS-CoV-2 was inactivated by UV-C light within 3 sec on both porous (disposable gown) and non-porous (stainless steel and apron) surfaces. For the porous surface, an irradiation of 5 min was needed to completely negative the PCR signal. The Z value estimating the sensitivity of SARS-CoV-2 to UV-C in the experimental conditions of our cabinet was shown to be > 0.5820 m2/J. These results illustrate the ability of this apparatus to inactivate rapidly and definitively high loads of SARS-CoV-2 deposited on porous or non-porous supports and open new perspectives on material decontamination using UV-C.

BackgroungTo cope with the persistence of the Covid-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially, and the heterologous ChadOx1-S/BNT162b2 regimen had shown better efficacy and immunogenicity than the homologous BNT162b2/BNT162b2 regimen.AimWe wanted to determine if this benefit was retained after the third dose.MethodsWe combined an observational study of SARS-COV-2 infections among vaccinated healthcare workers at the University-Hospital of Lyon, France, with an analysis of immunological parameters before and after the third mRNA vaccine dose.ResultsFollowing the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens, but this was no longer the case after the third dose. RBD-specific IgG levels and serum neutralization capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group.ConclusionThe advantage conferred by heterologous vaccination is lost after the third dose both in terms of protection and immunogenicity. Immunological measurements suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

ObjectivesWe aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS-CoV-2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients.MethodsAnti-RBD IgG levels and IFN-γ release were evaluated at PCR-diagnosis of SARS-CoV-2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods.ResultsMedian levels of anti-RBD IgG in positive patients were significantly lower than in negative patients for both variants (p< 0.05). The risk of Delta infection was inversely correlated with anti-RBD IgG titres (aOR = 0.63, 95% CI [0.41; 0.95],p= 0.03) and it was lower in the hybrid immunity group compared to the homologous vaccination group (aOR = 0.22, 95% CI [0.05; 0.62],p= 0.01). In contrast, neither the vaccination scheme nor anti-RBD IgG titers were associated with the risk of BA.1 infection in multivariable analysis. IFN-γ release post-SARS-CoV-2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p= 0.77).ConclusionsOur results show that high circulating levels of anti-RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS-CoV-2 infection in outpatients with differences according to the infecting variant.

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein–specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein–specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced T H 1 polarization of their SARS-CoV-2 spike protein–specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein–specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein–specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

The Secproch working group (for "securite des produits issus du corps humain") was created in 2019 within the « Haut Conseil de la sante publique » (HCSP) for addressing all the questions related to labile blood products, organs, tissues, cells (OTC) and gametes issued from human body. It is notably in charge of the management of alerts regarding arbovirus infections. These infections due to arthropod-transmitted viruses are responsible for emergence and reemergence, notably in the context of global warming. This review relates the alerts taken into consideration by the Secproch group between 2019 and 2021 following three pathologies due to Flaviviridae : dengue, West Nile virus (WNV) infection and tick-borne encephalitis (TBE). The dengue alerts have occurred in French Indies where the virus is endemic/epidemic, Reunion Island where the population was naive until 2018 towards the virus, and the metropole where foci of autochthonous cases are observed sporadically. The WNV infection was responsible of both human and equine cases in 2019 in the South of France but with intensity much less than in 2018. At last, the TBE virus was at the origin of a cluster of about 40 cases in the Ain department following a contamination by crude non-pasteurized goat cheese. This review offers the opportunity to reevaluate the risks linked to these three viruses through blood products and organs/tissues/cells and to precise the means recommended by HCSP to secure these products.

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities have recommended that patients under the age of 55 who received one dose of ChAdOx1-S-nCoV-19 vaccine receive a second dose of Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here, we show that the heterologous ChAdOx1-S-nCoV-19/BNT162b2 combination confers better protection against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection than the homologous BNT162b2/BNT162b2 combination in a real-world observational study of healthcare workers (n=13121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody (Ab) responses but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity, regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential was correlated with increased frequencies of switched and activated memory B cells recognizing the SARS-CoV-2 Receptor Binding Domain (RBD). The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immune compromised individuals.

To provide insight into the long-term immune response following bivalent vaccines, we sampled vaccinated patients simultaneously co-infected with Delta and BA.1. We reported that simultaneous exposure to the Delta and BA.1 S protein does not confer an additional immune advantage compared to exposure to the Omicron BA.1 S protein alone.

To provide insight into the long-term immune response following bivalent vaccines, we sampled vaccinated patients simultaneously co-infected with Delta and BA.1. We reported that simultaneous exposure to the Delta and BA.1 S protein does not confer an additional immune advantage compared to exposure to the Omicron BA.1 S protein alone.

Within the successive waves that occurred during the SARS-CoV-2 pandemic, recommendations arose to test symptomatic and contact subjects by using rapid antigen devices directed against the viral nucleocapsid protein with the aim to isolate contagious patients without delay. The objective of this study was to evaluate the ability of four rapid lateral-flow tests (RLFT) that were commercially available on the French market in 2022 to recognize various strains of SARS-CoV-2. Series of five-fold dilutions of seven viral suspensions belonging to different lineages of SARS-CoV-2 (19A, 20A, Alpha, Beta, Gamma, Delta and Omicron) were used to evaluate the analytical sensitivity of four commercially available RLFTs (manufacturers: Abbott, AAZ, Becton-Dickinson and Biospeedia). Cell culture and quantitative RT-PCR were used as references. Excellent correlations were observed for each lineage strain between the viral titer obtained via cell culture and the number of RNA copies measured by quantitative RT-PCR. Although the four tests were able to recognize all the tested variants, significant differences in terms of sensitivity were observed between the four RLFTs. Despite the limitation represented by the small number of devices and clinical isolates that were tested, this study contributed by rapidly comparing the sensitivity of SARS-CoV-2 RLFTs in the Omicron era.

Antigen‐specific T‐cells are essential for protective immunity against SARS‐CoV‐2. We set up a semi‐automated whole‐blood Interferon‐gamma release assay (WB IGRA) to monitor the T‐cell response after stimulation with SARS‐CoV‐2 peptide pools. We report that the WB IGRA is complementary to serological assays to assess SARS‐CoV‐2 immunity.

A comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs (p = 0.07). The proportion of HCWs with a viral load > 5.0 log10 cp/mL (Ct value 37). More than 90% of cultivable virus had a viral load > 4.5 log10 cp/mL (Ct

The virus neutralization test (VNT) is the reference for the assessment of the functional ability of neutralizing antibodies (NAb) to block SARS-CoV-2 entry into cells. New competitive immunoassays measuring antibodies preventing interaction between the spike protein and its cellular receptor are proposed as surrogate VNT (sVNT). We tested three commercial sVNT (a qualitative immunochromatographic test and two quantitative immunoassays named YHLO and TECO) together with a conventional anti-spike IgG assay (bioMérieux) in comparison with an in-house plaque reduction neutralization test (PRNT50) using the original 19A strain and different variants of concern (VOC), on a panel of 306 sera from naturally-infected or vaccinated patients. The qualitative test was rapidly discarded because of poor sensitivity and specificity. Areas under the curve of YHLO and TECO assays were, respectively, 85.83 and 84.07 (p-value >0.05) using a positivity threshold of 20 for PRNT50, and 95.63 and 90.35 (p-value =0.02) using a threshold of 80. However, the performances of YHLO and bioMérieux were very close for both thresholds, demonstrating the absence of added value of sVNT compared to a conventional assay for the evaluation of the presence of NAb in seropositive subjects. In addition, the PRNT50 assay showed a reduction of NAb titers towards different VOC in comparison to the 19A strain that could not be appreciated by the commercial tests. Despite the good correlation between the anti-spike antibody titer and the titer of NAb by PRNT50, our results highlight the difficulty to distinguish true NAb among the anti-RBD antibodies with commercial user-friendly immunoassays.

Since April 2022, a large number of monkeypox (MPX) cases have emerged across the globe in regions that are known to be totally free of zoonotic reservoir. The High Council for Public Health is a national institute commissioned to provide guidelines to the French Ministry of Health. The objective of these guidelines and recommendations is to inform the public, people at risk of severe MPX infection, infected patients and their families and contacts and healthcare workers in charge of infected patients.A review of the literature from the MEDLINE database was carried out using the single keyword 'monkeypox', including recent and older articles from January 2000 to June 2022. There was no filter for the type of study, except English language. The titles and summaries of all the articles were read by the experts to select articles of interest. The High Council for Public Health brought together specialists with expertise in the field to analyse the scientific literature and international recommendations. Recommendations were classified with clinical practice methodology using four levels (strong recommendation, recommendation, optional recommendation and no recommendation) without grading the level of evidence. To develop and methodologically validate the recommendations, the Appraisal of Guidelines for Research and Evaluation Instrument (AGREE-II)chart was partially used. QUESTIONS ADDRESSED BY THE GUIDELINES AND RECOMMENDATIONS: (a) What are the therapeutic management measures for hospitalized patients with severe forms of MPX infection, and what are the preventive measures to protect healthcare professionals? (b) What are the isolation and prevention measures in the community for patients with mild or moderate severity MPX infection? (c) what are the preventive measures for contacts of an MPX-infected person? (d) Who should be vaccinated? (e) What are the specific prevention measures for children and schools?

International audience; Our objective was to improve the accuracy of bacteria and resistance coding in a hospital case mix database. Data sources consisted of 50,074 files on bacteriological susceptibility tests transmitted with the HPRIM protocol from laboratory management system to electronic health record of the University hospital of Saint Etienne in July 2017. An algorithm was implemented to detect susceptibility tests containing information corresponding to codes whose addition in the case mix database was susceptible to increase the severity level of a diagnosis related group. Among 132 hospital stays fulfilling the conditions, 27 were lacking bacteria and/or resistance codes, and the tariff was increased for 9 stays, with earnings of €54,612. Analyzing Antimicrobial susceptibility tests helps to improve clinical coding and optimize the financial gain.

Our objective was to improve the accuracy of bacteria and resistance coding in a hospital case mix database. Data sources consisted of 50,074 files on bacteriological susceptibility tests transmitted with the HPRIM protocol from laboratory management system to electronic health record of the University hospital of Saint Etienne in July 2017. An algorithm was implemented to detect susceptibility tests containing information corresponding to codes whose addition in the case mix database was susceptible to increase the severity level of a diagnosis related group. Among 132 hospital stays fulfilling the conditions, 27 were lacking bacteria and/or resistance codes, and the tariff was increased for 9 stays, with earnings of €54,612. Analyzing Antimicrobial susceptibility tests helps to improve clinical coding and optimize the financial gain.

Periodontitis (PDT) has gained attention in the literature with the increase in life expectancy of people living with HIV on combined antiretroviral therapy (cART). Thus, the search for inflammatory biomarkers could be useful to understand the pathophysiology of chronic oral diseases in the cART era.The aim of this study was to evaluate the impact of non-surgical periodontal therapy (NSPT) on clinical parameters of PDT, Candida spp. count and expression of LF and HST in saliva and CGF of HIV-infected patients.Bleeding index (BI), probing depth (PD), clinical attachment level (CAL), colony-forming units (CFUs) of Candida spp, and lactoferrin (LF) and histatin (HST) levels were measured in saliva and GCF of both groups at three different times: baseline (before treatment), and 30 and 90 days after the NSPT. Clinical, mycological and immunoenzymatic analyses were also performed.Twenty-two HIV-infected patients and 25 non-HIV-infected patients with PDT participated in the study. NSPT was effective in improving periodontal clinical parameters, including ≤ 4 sites with PD ≤ 5mm and BI ≤ 10%. No significant change in oral Candida spp. count occurred neither between the two groups nor during the time after the periodontal treatment. And the salivary and GCF levels of LF and HST seems not to be influenced by the NSPT. By contrast, except for salivary LF, HST and LF were shown to exhibit significantly higher levels in HIV-infected than in non-HIV-infected patients.NSPT was effective in improving periodontal disease parameters in HIV-infected patients, but do not affect lactoferrin and histatin-5 expression in saliva and ginvival crevicular fluid of HIV-infected patients.

Vaccine hesitancy (VH) is defined as “delaying or refusing a secure vaccine despite its availability”. This hesitancy affects caregivers and more specifically nurses. The purpose of this study is to assess determinants of influenza VH in the nurse’s community. We conducted a systematic review of qualitative literature according to criteria of Preferred Reporting Items for Systematic Review and Meta-Analysis and Enhancing Transparency in Reporting the synthesis of Qualitative Research from 2009 until October 2020. Eleven qualitative studies analysed (ten thematic content analyses and one grounded theory method) found three main factors in VH. The first determinant was the benefit–risk equation considered as unfavourable due to an ineffective vaccine and fears about adverse effects as the pain of the injection. Wrong immunological beliefs brought into hesitancy. Disease barriers (hand washing and masks) and personal immunity were regarded as more effective than the vaccine. Lastly, dehumanised vaccination and the difficulties of access to healthcare were institutional determinants. Nurses ask for a vaccine promotion by hierarchy and doctors with transparent information and respect for autonomy. The availability of vaccines and methods of pain control seem to be some tracks to reduce nurses’ VH.

Background The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19. Methods 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of 9 commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement, and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers. Results The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0–68.1) for bioMérieux IgM to 91.2% (87.0–94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1–48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7–89.7), 90.3% (78.1–96.1), and 96.8% (86.8–99.3) for Siemens, bioMérieux IgG, and DiaSorin, respectively. None of the commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC Conclusions Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests, including those targeting the RBD, cannot substitute a VNT for the assessment of functional antibody response.

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

Bone and joints infections represent a potentially devastating complication of prosthetic orthopaedic joint replacement, thus requiring both rapid and appropriate antibiotic treatment. Staphylococcus aureus is one of the most frequent pathogens involved in this pathology. Being able to assert its presence is the first step of patients' efficient management. This monocenter study was aimed at evaluating the MRSA/SA ELITe MGB assay for the molecular detection of S. aureus and methicillin-resistant S. aureus (MRSA) in bone and joint biopsies and synovial fluids. This test together with conventional techniques including standard cultures and 16S rRNA amplification assay were performed on 208 successive perioperative samples collected prospectively for one year from 129 patients. Using conventional techniques, a microbial pathogen was detected in 76 samples from 58 patients, out of which 40 were identified as S. aureus. The limit of detection (LOD) of the MRSA/SA ELITe MGB assay was experimentally determined for bone and joint biopsies and synovial fluids using negative samples spiked with S. aureus ATCC43300. The sensitivity of S. aureus detection with the MRSA/SA ELITe MGB assay was 82.5% (33/40 samples) and 97.5% (39/40 samples) using manufacturer's LOD and experimentally determined LOD respectively. Interestingly using the osteo-articular specific LOD, 15 additional samples were detected positive for S. aureus DNA with the MRSA/SA ELITe MGB assay; in all cases, those samples were taken from patients considered to be infected with S. aureus according to their clinical and microbiological records. The results were available within 24h, which could help to shorten the therapeutic decisions.

We conducted a prospective study in healthcare workers (n=296) of the University Hospital of Lyon, France. Serum samples (n=296) collected six months after disease onset were tested using three commercial assays: the Wantai Ab assay detecting total antibodies against the receptor binding domain (RBD) of the S protein, the bioMerieux Vidas assay detecting IgG to the RBD and the Abbott Architect assay detecting IgG to the N protein. The neutralising antibody (NAb) titre was also determined for all samples with a virus neutralisation assay (VNA) using live virus. The positivity rate was 100% with the Wantai assay, 84.8% with the bioMerieux assay and 55.4% with the Abbott assay. Only 51% of HCWs were positive for the presence of NAb. Less than 10 % of HCWs had a NAb titre greater than 80. At a neutralising titre of 80, the area under the curves [IC 95%] was 0.71 [0.62-0.81], 0.75 [0.65-0.85] and 0.95 [0.92-0.97] for Wantai, Abbott and Vidas respectively. The data presented herein suggest that commercial assays detecting antibodies against the N protein must not be used in long-term seroprevalence surveys while the Wantai assay could be useful for this purpose. VNA should remain the gold standard to assess the protective antibody response, but some commercial assays could be used as first-line screening of long-term presence of NAb.

Background Despite vaccination programs, Streptococcus pneumoniae remains among the main microorganisms involved in bacterial pneumonia, notably in terms of severity. The prognosis of pneumococcal infections is conditioned in part by the precocity of the diagnosis. The aim of this study was to evaluate the impact of a Rapid Diagnostic Test (RDT) targeting cell wall polysaccharide of Streptococcus pneumoniae and performed directly in respiratory samples, on the strategy of diagnosis of respiratory pneumococcal infections in children. Results Upper-respiratory tract samples from 196 children consulting at hospital for respiratory infection were tested for detecting S. pneumoniae using a newly-designed RDT (PneumoResp, Biospeedia), a semi-quantitative culture and two PCR assays. If positive on fluidized undiluted specimen, the RDT was repeated on 1:100-diluted sample. The RDT was found highly specific when tested on non-S. pneumoniae strains. By comparison to culture and PCR assays, the RDT on undiluted secretions exhibited a sensitivity (Se) and negative predictive value (NPV) of more than 98%. By comparison to criteria of S. pneumoniae pneumonia combining typical symptoms, X-ray image, and culture ≥107 CFU/ml, the Se and NPV of RDT on diluted specimens were 100% in both cases. Conclusions In case of negative result, the excellent NPV of RDT on undiluted secretions allows excluding S. pneumoniae pneumonia. In case of positive result, the excellent sensitivity of RDT on diluted secretions for the diagnosis of S. pneumoniae pneumonia allows proposing a suitable antimicrobial treatment at day 0.

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.

Background The issue of contact precautions as contributory factors for reducing Pseudomonas aeruginosa (Pa) infections in intensive care units (ICUs) remains questioned. We evaluated the impact of the addition of contact precautions to standard precautions for Pa-positive patients on incidence of ICU-acquired Pa infections. Methods In this multicenter, cluster-randomized crossover trial, 10 French ICUs were randomly assigned (1:1) to sequence 0–1 (6-month control period [CP]/3-month washout period/6-month intervention period [IP]) or sequence 1–0 (6-month IP/3-month washout period/6-month CP). A surveillance screening program for Pa was implemented. Competing-risks regression models were built with death and discharge without the occurrence of ICU-acquired Pa infection (the primary outcome) as competing events. Models were adjusted for within-ICU correlation and patient- and ICU-level covariates. The Simpson diversity index (SDI) and transmission index (TI) of Pa isolates were derived from pulsed-field gel electrophoresis typing. Results Within recruited ICUs, the cumulative incidence and incidence rate of ICU-acquired Pa infections were 3.38% (55/1625) versus 3.44% (57/1658) and 3.31 versus 3.52 per 1000 patient-days at risk during the CP and IP, respectively. Multivariable models indicated that the intervention did not significantly change the cumulative incidence (subdistribution hazard ratio, .91; 95% confidence interval [CI], .49–1.67; P = .76) or rate (cause-specific hazard ratio, 1.36; 95% CI, .71–2.63; P = .36) of the primary outcome. SDI and TI did not significantly differ between CP and IP. Conclusions The addition of contact precautions to standard precautions for Pa-positive patients with a surveillance screening program does not significantly reduce ICU-acquired Pa infections in non-outbreak situations. Clinical Trials Registration. ISRCTN92710225.

Following human immunodeficiency virus-1 (HIV-1) infection and antiretroviral therapy, the development of periodontal disease was shown to be favored. However, the influence of HIV-1 infection on the periodontal microbiota after non-surgical periodontal debridement (NSPD) needs a broad comprehension. This work aimed to compare the subgingival microbiological content of patients infected with HIV-1 and controls (non-infected) with periodontitis undergoing NSPD.The bacterial profile of subgingival biofilm samples of patients with HIV-1 (n = 18) and controls (n = 14) with periodontitis was assessed using 16S rRNA gene sequencing. The samples were collected at baseline, 30, and 90 days after NSPD. The taxonomic analysis of gingival microbiota was performed using a ribosomal RNA database. The microbiota content was evaluated in the light of CD4 cell count and viral load.Both HIV and control groups showed similar stages and grades of periodontitis. At baseline, the HIV group showed higher alpha diversity for both healthy and periodontal sites. Streptococcus, Fusobacterium, Veillonella and Prevotella were the predominant bacterial genera. A low abundance of periodontopathogenic bacteria was observed, and the NSPD induced shifts in the subgingival biofilm of patients with HIV-1, leading to a microbiota similar to that of controls.Different subgingival microbiota profiles were identified-a less diverse microbiota was found in patients infected with HIV-1, in contrast to a more diverse microbiota in controls. NSPD caused changes in the microbiota of both groups, with a greater impact on the HIV group, leading to a decrease in alpha diversity, and produced a positive impact on the serological immune markers in patients infected with HIV-1. Control of periodontitis should be included as part of an oral primary care, providing the oral health benefits and better control of HIV-1 infection.

The sensitivity of NG-test CTX-M Multi assay and BL-RED test incubated 10 min for the detection of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae was 80.6% and 90.3% respectively. Using an extended 60 min incubation with the BL-RED test, its sensitivity was increased to 100% and 60.9% for ESBL-producing and cephalosporinase-overexpressing Enterobacteriaceae respectively.

(1) Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the intestines, which participates in human cytomegalovirus (HCMV) reactivation from its latent reservoir. CMV-associated colitis plays a pejorative role in the clinical course of UC. We took advantage of a model of chemically induced enteritis to study the viral reactivation of murine CMV (MCMV) in the context of gut inflammation. (2) Methods: Seven-week-old BALB/c mice were infected by 3 × 103 plaque-forming units (PFU) of MCMV; 2.5% (w/v) DSS was administered in the drinking water from day (D) 30 to D37 post-infection to induce enteritis. (3) Results: MCMV DNA levels in the circulation decreased from D21 after infection until resolution of the acute infection. DSS administration resulted in weight loss, high disease activity index, elevated Nancy index shortening of the colon length and increase in fecal lipocalin. However, chemically induced enteritis had no impact on MCMV reactivation as determined by qPCR and immunohistochemistry of intestinal tissues. (4) Conclusions: Despite the persistence of MCMV in the digestive tissues after the acute phase of infection, the gut inflammation induced by DSS did not induce MCMV reactivation in intestinal tissues, thus failing to recapitulate inflammation-driven HCMV reactivation in human UC.

Individuals with pre-existing chronic systemic low-grade inflammation are prone to develop severe COVID-19 and stronger anti-SARS-CoV-2 antibody responses. Whether this phenomenon reflects a differential expansion of antiviral B cells or a failure to regulate antibody synthesis remains unknown. Here, we compared the antiviral B cell repertoire of convalescent healthcare personnel to that of hospitalized patients with pre-existing comorbidities. Out of 277,500 immortalized B cell clones, antiviral B cell frequencies were determined by indirect immunofluorescence screening on SARS-CoV-2 infected cells. Surprisingly, frequencies of SARS-CoV-2 specific clones from the two groups were not statistically different, despite higher antibody levels in hospitalized patients. Moreover, functional analyses revealed that several B cell clones from healthcare personnel with low antibody levels had neutralizing properties. This study reveals for the first time a key qualitative defect of antibody synthesis in severe patients and calls for caution regarding estimated protective immunity based only on circulating antiviral antibodies.

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.

Background The World Health Organization (WHO) aims to achieve global hepatitis C elimination by 2030, defined as diagnosis of 90% of infected individuals and treating 80% of them. Current guidelines for the screening and diagnosis of hepatitis C infection denote using a relatively cheap screen with anti-hepatitis C virus (HCV) antibody immunoassay, followed by the much costlier molecular test for HCV RNA levels using polymerase chain reaction (PCR) assay to confirm active HCV infection. Simplification of the HCV evaluation algorithm to reduce the number of required tests could considerably expand the provision of HCV treatment especially in a developing country. This study investigates the performance of hepatitis C Core Antigen (HCV Ag) test by comparing HCV Ag results versus the results obtained with HCV ribonucleic acid (RNA) PCR which is considered the gold standard for the diagnosis of HCV infection. Results Among the 109 anti-HCV positive sera, 96 were positive for both HCV Ag (> 3 fmol/L) and HCV RNA (> 15 IU/mL); 8 were negative for both tests, while the remaining 5 were positive for HCV RNA only. Considering the HCV RNA as gold standard; the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HCV Ag test were found to be 95.05%, 100%, 100%, and 61.54%, respectively. HCV genotype was performed for 59 patients. The most common HCV genotype was genotype 1 (72.9%). Genotype 2 (15.3%) and genotype 3 (11.9%) were detected in the others samples. A high level of correlation was seen between HCV RNA and HCV Ag (r = 0.958, p < 0.001). The correlation for the samples that were genotyped 1 was significant (r = 0.966, p < 0.001). Conclusion In our study, it was found that there was strong correlation between HCV RNA levels and HCV Ag levels. So, it can be used for a one-step HCV antigen test to diagnose active HCV infection.

Background Despite combined antiretroviral therapy (cART), total cure of immunodeficiency virus type 1 (HIV-1) infection remains elusive. Chronic periodontitis (CP) is strongly associated with HIV-1 infection. This condition is characterized by an intense inflammatory infiltrate mainly constituted of immune cells which in turn may be a valuable source of HIV-1 reactivation. This study aimed to determine if gingival tissue could act as a reservoir for HIV-1. Methods Twelve HIV-1-infected patients with CP and 12 controls (no HIV-1-infection and no CP) were evaluated in a cross-sectional study. RNA viral load and interleukin (IL) levels were determined in blood plasma and saliva. Histological sections of gingival tissue were stained with fluorescent antibodies against p24 antigen and different cellular biomarkers. Results In 6 of the 12 patients, HIV RNA load was detected, despite cART; in three of them, expression of viral RNA was also detected in saliva. The levels of IL-2, IL-6 and IL-12 were higher in blood and saliva of HIV-infected patients with CP than controls. HIV-1 p24 antigen was detected by Immunostaining in gingival biopsies of 10 of the 12 patients but in no control. Immune markers for T cells and antigen-presenting cells were also identified in most patients and some controls. Conclusion These preliminary data showing the detection of HIV-1 p24 antigen in the gingival biopsies of a significant part of HIV-1 infected patients with CP under cART together with the presence of immune cells, plead for the existence of a HIV-1 reservoir in the gingival tissue of this population. This article is protected by copyright. All rights reserved.

IntroductionEnd stage kidney disease (ESKD) and cancer have been identified as risk factors for severe and fatal cases of COVID-19, making vaccination in these patients a priority. Patients suffering from ESKD have a significantly weaker response to common vaccines than general population. However, humoral and cellular immune responses after two doses of RNA-based vaccine BNT162b2 (Pfizer–BioNTech) have been poorly explored in this vulnerable population.Case presentationA 69-year-old male patient was followed for ESKD and myeloma. He developed a severe SARS-CoV-2 pneumonia twenty days after two doses of BNT162b2 vaccine. Whole genome sequencing found that the virus belonged to the 20I/501Y.V1 clade. A serology draws eight days after the 2nd vaccine dose showed positive RBD IgG without neutralizing activity. A serum specimen sampled thirty days after the onset of SARS-CoV-2 infection showed seroconversion against both RBD and N antigens. This specimen was shown to exhibit a frank neutralizing activity. The QuantiFERON® SARS-CoV-2 (Qiagen) showed a positive specific cellular response although the QuantiFERON monitor displayed a weak cellular response. ConclusionsImpaired immunity due to renal failure probably explain the severe pneumonia despite vaccination. The fact that the patient developpe a neutralizing activity and a cellular response after a third stimulation by infection may suggest to systemically administrate a third dose of vaccine in ESKD patients.

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.

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.

The aim of this study was to investigate the relationship between nasal and rectal Staphylococcus aureus carriage in intensive care unit (ICU) patients and the occurrence of ICU-acquired infections related to S. aureus carriage. Three hundred and ninety-five patients admitted in ICU were screened for S. aureus nasal and rectal carriages and followed to record S. aureus infections during their stay. S. aureus strains were genotyped by arbitrarily primed PCR, spa-typing, microarray and whole genome sequencing. At ICU admission, 112 of 363 (30.9%) patients carried S. aureus including 61 (16.8%) exclusive nasal carriers, 40 (11.0%) combined nasal and rectal carriers and 11 (3.0%) exclusive rectal carriers. The 152 S. aureus isolates from nasal and rectal swabs belonged to 19 clonal complexes (CCs). Patients colonized in both nose and rectum harboured different strains in at least 40% of cases according to arbitrarily primed PCR data. Nasal carriers of CC5 S. aureus had an increased risk of rectal carriage (RR = 1.85, P

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.

Viral infections of the respiratory tract can be complicated by bacterial superinfection, resulting in a significantly longer duration of illness and even a fatal outcome. In this review, we focused on interactions between S. aureus and non-influenza viruses. Clinical data evidenced that rhinovirus infection may increase the S. aureus carriage load in humans and its spread. In children, respiratory syncytial virus infection is associated with S. aureus carriage. The mechanisms by which some non-influenza respiratory viruses predispose host cells to S. aureus superinfection can be summarized in three categories: i) modifying expression levels of cellular patterns involved in S. aureus adhesion and/or internalization, ii) inducing S. aureus invasion of epithelial cells due to the disruption of tight junctions, and iii) decreasing S. aureus clearance by altering the immune response. The comprehension of pathways involved in S. aureus-respiratory virus interactions may help developing new strategies of preventive and curative therapy.

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.