Human immunodeficiency virus and oral microbiota: mutual influence on the establishment of a viral gingival reservoir in individuals under antiretroviral therapy.

The role of the oral microbiota in the overall health and in systemic diseases has gained more importance in the recent years, mainly due to the systemic effects that are mediated by the chronic inflammation caused by oral diseases, such as periodontitis, through the microbial communities of the mouth. The chronic infection by the human immunodeficiency virus (HIV) interacts at the tissue level (e.g. gut, genital tract, brain) to create reservoirs; the modulation of the gut microbiota by HIV infection is a good example of these interactions. The purpose of the present review is to assess the state of knowledge on the oral microbiota (microbiome, mycobiome and virome) of HIV-infected patients in comparison to that of HIV-negative individuals and to discuss the reciprocal influence of HIV infection and oral microbiota in patients with periodontitis on the potential establishment of a viral gingival reservoir. The influence of different clinical and biological parameters are reviewed including age, immune and viral status, potent antiretroviral therapies, smoking, infection of the airway and viral coinfections, all factors that can modulate the oral microbiota during HIV infection. The analysis of the literature proposed in this review indicates that the comparisons of the available studies are difficult due to their great heterogeneity. However, some important findings emerge: (i) the oral microbiota is less influenced than that of the gut during HIV infection, although some recurrent changes in the microbiome are identified in many studies; (ii) severe immunosuppression is correlated with altered microbiota and potent antiretroviral therapies correct partially these modifications; (iii) periodontitis constitutes a major factor of dysbiosis, which is exacerbated in HIV-infected patients; its pathogenesis can be described as a reciprocal reinforcement of the two conditions, where the local dysbiosis present in the periodontal pocket leads to inflammation, bacterial translocation and destruction of the supporting tissues, which in turn enhances an inflammatory environment that perpetuates the periodontitis cycle. With the objective of curing viral reservoirs of HIV-infected patients in the future years, it appears important to develop further researches aimed at defining whether the inflamed gingiva can serve of viral reservoir in HIV-infected patients with periodontitis.

Prospective Evaluation of the BD MAX StaphSR Assay for the Screening of Methicillin-Susceptible and -Resistant Staphylococcus aureus from Nasal Swabs Taken in Intensive Care Unit Patients.

Screening patients for S. aureus nasal carriage has proved effective in preventing cross-contamination and endogenous infection with this bacterium. The aim of this study was to assess the performance of the BD MAX StaphSR assay with liquid Amies elution swabs, taken during routine care of intensive care unit patients. Direct and pre-enriched cultures were used as reference methods to screen for S. aureus and methicillin-resistant S. aureus (MRSA). Discrepant results between the BD MAX StaphSR assay and cultures were resolved by using the Xpert SA Nasal Complete assay. A total of 607 nasal swabs taken from 409 patients were included in this study. Compared to culture methods, the sensitivity and specificity of the BD MAX StaphSR assay were 92.5% and 91.7% for S. aureus screening, and 94.7% and 98.3% for MRSA screening, respectively. In 52 (8.6%) specimens, there was a discrepancy between the results of cultures and the BD MAX StaphSR assay, including 13 (25%) where the results of the BD MAX StaphSR assay were confirmed by the Xpert SA Nasal Complete test. This prospective study showed that the BD MAX StaphSR assay is reliable for S. aureus and MRSA detection from nasal samples taken with liquid Amies elution swabs.

[Viruses present in the environment: virological considerations and examples of their impact on human health]. / Les virus dans l'environnement, considérations virologiques et exemples de leur impact en santé humaine.

Animal viruses are present in most human environments. Their viability in these media is very variable and the most important element that conditions this viability is the existence or not of a phospholipid envelope surrounding the nucleocapsid. After some general considerations on the structure of viruses, their multiplication cycle and their resistance to different physico-chemical agents, some examples of the impact of animal viruses present in the environment on human health will be presented. The situations that are related concern recent epidemiological events: circulation of type 2 polioviruses derived from the Sabin vaccine strain in the wastewater of New York, London and Jerusalem; risk of transmission of Sars-CoV-2 during the spreading of sludge from wastewater treatment plants on agricultural land in the era of the Covid-19 pandemic; « new ¼ forms of food-borne poisoning of viral origin (hepatitis E, tick-borne encephalitis, Nipah virus infection); contamination by epidemic viruses of mobile phones used by pediatricians; role of fomites in the spread of orthopoxvirus infections (smallpox, cowpox, monkeypox). The risk attached to animal viruses present in the environment must be assessed in a measured way without overestimating or underestimating their potential consequences for human health.

Impact of Dextran-Sodium-Sulfate-Induced Enteritis on Murine Cytomegalovirus Reactivation.

(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.

Evaluation of Rapid Lateral-Flow Tests Directed against the SARS-CoV-2 Nucleoprotein Using Viral Suspensions Belonging to Different Lineages of SARS-CoV-2.

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.

Outbreak of central nervous system infections among children in Thai Binh, Viet Nam.

From July to October 2020, 99 cases of central nervous system (CNS) infections were identified in Thai Binh Pediatric Hospital, Viet Nam, representing a five-fold increase compared to the baseline incidence during the previous five years. Clinical data were retrospectively collected. Cerebrospinal fluid specimens (CSF) were secondarily tested for pathogens using viral culture and PCR assays. Patient median age was 5 years (0-12 years); 58.6% were male. Of these children, 83.8% had CSF white blood culture (WBC) counts of ≥ 10 cells/µL, including 58 of 99 (58.6%) with a WBC count ≥ 100 cells/µL. Overall, 72 (72.7%) patients had confirmed infections with a pathogen identified in the CSF, the majority of which (66) were enterovirus. Sequencing results suggested that the rise of incidence observed in 2020 was due to Echovirus 4 (n = 45), Echovirus 30 (n = 8), and Echovirus 6 (n = 1) circulation. A confirmed CNS infection was significantly associated with older age (≥5 years, OR = 3.64, p = 0.03) and with an increased WBC count in the CSF (OR = 6.38, p-value = 0.01 for WBCs from 10 to <100 and OR = 7.90, p-value = 0.002 for WBCs ≥100). Ninety-seven (97) of 99 (98.0%) children received empiric antimicrobial treatment, and 35 (35.3%) were treated with multiple antibiotics. Eighty-four (84) patients (84.9%) were discharged home, and 11 (11.1%) were transferred to the National Hospital because their condition had worsened. No deaths were recorded. Point-of-care tests, including real-time PCR assays to identify common pathogens, should be implemented for more accurate diagnosis and more appropriate antibiotic use.

Evaluating the Increased Burden of Cardiorespiratory Illness Visits to Adult Emergency Departments During Flu and Bronchiolitis Outbreaks in the Pediatric Population: Retrospective Multicentric Time Series Analysis.

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, P<.001; CHU Grenoble: χ23=126.67, P<.001) and were quite dependent in both hospital settings (CHU Saint Etienne: Spearman ρ=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.

Exploration of the ocular surface infection by SARS-CoV-2 and implications for corneal donation: An ex vivo study.

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/.

Epidemiological and clinical insights from SARS-CoV-2 RT-PCR crossing threshold values, France, January to November 2020.

BackgroundThe COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.AimWe explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.MethodsWe used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.ResultsAlthough we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.ConclusionOur results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.

Prospective evaluation of the point-of-care use of a rapid antigenic SARS-CoV-2 immunochromatographic test in a paediatric emergency department.

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.

Evidence of HIV-1 Genital Shedding after One Year of Antiretroviral Therapy in Females Recently Diagnosed in Bamako, Mali.

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.

Evaluation of in vitro activity of copper gluconate against SARS-CoV-2 using confocal microscopy-based high content screening.

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.

Characteristics of the delayed respiratory syncytial virus epidemic, 2020/2021, Rhône Loire, France.

The Rhône-Loire metropolitan areas' 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.

Live virus neutralization testing in convalescent patients and subjects vaccinated against 19A, 20B, 20I/501Y.V1 and 20H/501Y.V2 isolates of SARS-CoV-2.

SARS-CoV-2 mutations appeared recently and can lead to conformational changes in the spike protein and probably induce modifications in antigenicity. We assessed the neutralizing capacity of antibodies to prevent cell infection, using a live virus neutralization test with different strains [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)] in serum samples collected from different populations: two-dose vaccinated COVID-19-naive healthcare workers (HCWs; Pfizer-BioNTech BNT161b2), 6-months post mild COVID-19 HCWs, and critical COVID-19 patients. No significant difference was observed between the 20B and 19A isolates for HCWs with mild COVID-19 and critical patients. However, a significant decrease in neutralization 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 neutralizing antibody titers in comparison with the 19A isolate. Interestingly, a significant difference in neutralization capacity was observed for vaccinated HCWs between the two variants but not in the convalescent groups.

Low rate of oseltamivir prescription among adults and children with confirmed influenza illness in France during the 2018-19 influenza season.

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 < 0.001]. Factors associated with oseltamivir prescription were evaluated in 729 patients (246 adults and 483 children). Patients with at least one risk factor for severe influenza received oseltamivir less frequently (50%, 137/274) than those without risk factors (70%, 315/452) (P < 0.001). Pregnant women received oseltamivir in 81% of cases (17/21). Severe influenza cases were treated with oseltamivir in only 45.3% (39/86). The median duration of symptoms was 24 h (IQR 12-48) in treated patients versus 72 h (IQR 48-120) in untreated patients (P < 0.01). 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.

A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity.

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, 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 samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

Incidence of Asymptomatic and Symptomatic Influenza Among Healthcare Workers: A Multicenter Prospective Cohort Study.

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.

Bacterial and Viral Infection in Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Implication for Antimicrobial Management and Clinical Outcome.

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 107 CFU/ml) and for the detection of viral genome and DNA of atypical bacteria by quantitative PCR using two commercial multiplex respiratory kits (Seegene and Fast-track). The two kits exhibited very similar performances although the Seegene assay was a bit more sensitive. A large number and variety of pathogens were recovered from the sputum samples of these 84 patients, including 15 conventional bacteria, one Chlamydia pneumoniae and 63 respiratory viruses, the most prevalent being rhinoviruses (n = 33) and influenza viruses (n = 13). From complete results available for 74 patients, the presence of bacteria was significantly associated with risk of recurrence at 6 and 12 months post-infection. The combination of these different markers appears useful for delineating correctly the antimicrobial treatment and for initiating a long-term surveillance in those patients with high risk of recurrent exacerbation episodes. A prospective study is required for confirming the benefits of this strategy aimed at improving the stewardship of antibiotics.