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A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant's environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS. [ABSTRACT FROM AUTHOR]

Seoul virus (SEOV), a hantavirus and the etiologic agent of a mild-to-moderate hemorrhagic fever with a renal syndrome, is associated worldwide with brown rats (Rattus norvegicus), a commensal rodent that [...]

The LDL receptor (LDL-R) has been proposed as the viral receptor for Hepatitis C virus (HCV). This hypothesis has been based exclusively on in vitro studies. In human mononuclear cells, LDL-R gene expression has been demonstrated to be parallel and be coordinately regulated to gene expression in the human liver. The purpose of the current study was to determine the mononuclear cell surface expression of the LDL receptor in patients with HCV chronic infection according to viral load. Sixty-eight consecutive untreated chronic hepatitis C patients were studied to determine the mononuclear cell surface expression of the LDL-R. LDL-Rs were quantified at the surface of mononuclear cells in fresh blood samples taken after fasting using flow cytometry. LDL-R expression was significantly associated with LDL-cholesterol (r = -0.25; P = 0.03) and HCV-viral load (r = 0.37, P = 0.002). In multivariate analysis, the LDL-R expression was significantly associated with HCV viral load, whereas genotype, age, body mass index, and fibrosis were not. In conclusion, our data provided by a human study, suggest that the LDL-R may be one of the receptors implicated in HCV replication. fibrosis; lipoproteins; cytometry doi:10.1152/ajpendo.00091.2007

Background: COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19).Methods: Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared.Results: COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations.Conclusion: CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach.Trial Registration: ClinicalTrials.gov, NCT03955887. [ABSTRACT FROM AUTHOR]

Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE. Forty-eight patients with wAIHA were included, among whom 26 (54%) had secondary wAIHA. Eleven (23%) patients presented at least one VTE, that occurred during an active phase of the disease for 10/11 patients (90%). The frequency of VTE was not different between primary and secondary AIHA (23.7 vs. 19.2%; p = 0.5). The Padua prediction score based on traditional risk factors was not different between patients with and without VTE. On multivariate analysis, total bilirubin ≥ 40 μmol/L [odds ratio (OR) = 7.4; p = 0.02] and leucocyte count above 7x109/L (OR = 15.7; p = 0.02) were significantly associated with a higher risk of thrombosis. Antiphospholipid antibodies were screened in 9 out the 11 patients who presented a VTE and were negative. Thus, the frequency of VTE is high (23%) during wAIHA and VTE preferentially occur within the first weeks of diagnosis. As no clinically relevant predictive factors of VTE could be identified, the systematic use of a prophylactic anticoagulation should be recommended in case of active hemolysis and its maintenance after hospital discharge should be considered. The benefit of a systematic screening for VTE and its procedure remain to be determined. [ABSTRACT FROM AUTHOR]

Background: The emergence of new strains in RNA viruses is mainly due to mutations or intra and inter-genotype homologous recombination. Non-homologous recombinations may be deleterious and are rarely detected. In previous studies, we identified HCV-1b strains bearing two tandemly repeated V3 regions in the NS5A gene without ORF disruption. This polymorphism may be associated with an unfavorable course of liver disease and possibly involved in liver carcinogenesis. Here we aimed at characterizing the origin of these mutant strains and identifying the evolutionary mechanism on which the V3 duplication relies. Methods: Direct sequencing of the entire NS5A and E1 genes was performed on 27 mutant strains. Quasispecies analyses in consecutive samples were also performed by cloning and sequencing the NS5A gene for all mutant and wild strains. We analyzed the mutant and wild-type sequence polymorphisms using Bayesian methods to infer the evolutionary history of and the molecular mechanism leading to the duplication-like event. Results: Quasispecies were entirely composed of exclusively mutant or wild-type strains respectively. Mutant quasispecies were found to have been present since contamination and had persisted for at least 10 years. This V3 duplication-like event appears to have resulted from non-homologous recombination between HCV-1b wild-type strains around 100 years ago. The association between increased liver disease severity and these HCV-1b mutants may explain their persistence in chronically infected patients. Conclusions: These results emphasize the possible consequences of non-homologous recombination in the emergence and severity of new viral diseases. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

In the autumn of 2020, a short-lived epidemic of a spike del69-70 deletion variant of SARS-CoV-2 was identified, with most cases (n = 95) found in Montceau-les-Mines, France. This spike gene target failure (SGTF) variant spread quickly in nursing homes. The Alpha variant, which also harbors this deletion, appeared in Burgundy in January 2021 after the disappearance of the Montceau-les-Mines del69-70 variant. Our findings illustrate the risk of the fast spread of geographically isolated variants and reinforce the need for the continuous tracking of outbreaks. In some cases, these studies may reveal emerging variants that affect public health or vaccine development. [ABSTRACT FROM AUTHOR]

The LDL receptor (LDL-R) has been proposed as the viral receptor for Hepatitis C virus (HCV). This hypothesis has been based exclusively on in vitro studies. In human mononuclear cells, LDL-R gene expression has been demonstrated to be parallel and be coordinately regulated to gene expression in the human liver. The purpose !f the current study was to determine the mononuclear cell surface expression of the LDL receptor in patients with HCV chronic infection according to viral load. Sixty-eight consecutive untreated chronic hepatitis C patients were studied to determine the mononuclear cell surface expression of the LDL-R. LDL-Rs were quantified at the surface of mononuclear cells in fresh blood samples taken after fasting using flow cytometry. LDL-R expression was significantly associated with LDL-cholesterol (r = -0.25; P = 0.03) and HCV-viral load (r = 0.37, P = 0.002). In multivariate analysis, the LDL-R expression was significantly associated with HCV viral load, whereas genotype, age, body mass index, and fibrosis were not. In conclusion, our data provided by a human study, suggest that the LDL-R may be one of the receptors implicated in HCV replication. [ABSTRACT FROM AUTHOR]

Objectives: A prospective study was performed to assess the intermediate and long-term efficacy of intralesional cidofovir therapy associated with surgical excision in laryngeal papillomatosis in adults. Methods: Endoscopy with intralesional injection of cidofovir 5 mg/mL was performed 3 times at 4-week intervals. The concentration was later increased to 7.5 mg/mL and the interval between injections shortened to 2 weeks. Further treatment was performed at 3 or 6 months, depending on the evolution of the papillomas. After complete remission, the treatment was stopped and the patients were reviewed every 6 months. Results: Nineteen patients completed the protocol, with a mean of 4.5 injections each. Complete remission was obtained in 17 cases (89%) after a mean of 3.8 procedures. Remission was stable after a mean follow-up of 24 months (range, 8 to 57 months). With higher cidofovir concentrations at shorter intervals, patients needed fewer injections to achieve remission (mean, 2.1 versus 4.7 injections). Conclusions: The effectiveness of intralesional cidofovir therapy in adult-onset recurrent respiratory papillomatosis was impressive. Once obtained, complete remission was stable on intermediate or long-term follow-up. The concentration and the interval between injections seemed to influence the number of injections necessary to achieve remission. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis.Methods: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared.Results: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation.Conclusion: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about disproving hepatitis C virus as a causative factor of diabetes mellitus.

This meta -analysis aimed to estimate the prevalence of human metapneumovirus (hMPV) infections in patients hospitalized for acute respiratory infection (ARI) and to study factors associated with this prevalence. Medline and ScienceDirect databases were searched for prospective observational studies that screened hospitalized patients with ARI for hMPV by RT-PCR, with data available at December 27, 2014. The risk of bias was assessed regarding participation rate, definition of ARI, description of diagnostic technique, method of inclusion identical for all subjects, standardized and identical sampling method for all subjects, analysis performed according to the relevant subgroups, and presentation of data sources. Random-effect meta -analysis with arcsine transformation and meta -regressions was used. In the 75 articles included, the prevalence of hMPV among hospitalized ARI was 6.24% (95% CI 5.25–7.30). An effect of the duration of the inclusion period was observed (p = 0.0114), with a higher prevalence of hMPV in studies conducted during periods of 7–11 months (10.56%, 95% CI 5.97–16.27) or complete years (7.55%, 95% CI 5.90–9.38) than in periods of 6 months or less (5.36%, 95% CI 4.29–6.54). A significant increase in the incidence with increasing distance from the equator was observed (p = 0.0384). hMPV should be taken into account as a possible etiology in hospitalized ARI. [ABSTRACT FROM AUTHOR]

Objective. – To evaluate the diagnostic usefulness of routine Lyme serology in patients who live in nonendemic areas and present with early inflammatory joint disease.Methods. – All patients admitted to a rheumatology department of a nonendemic area of France for evaluation of joint disease with onset within the last year. The evaluation included a medical history, a thorough physical examination, an electrocardiogram, and an ELISA for antibodies to Borrelia burgdorferi.Results. – We included 90 patients, 51 women and 39 men, with a mean age of 48.1 ± 17.9 years. Mean duration of joint symptoms was 4.3 ± 4.3 months, with a median of 3 months. A patient (1.1%) reported a tick bite and no patients had a history of erythema migrans. Lyme serology was negative in all 90 patients.Conclusion. – These results do not support routine Lyme serology in patients living in nonendemic areas and presenting with early inflammatory joint disease. However, Lyme serology remains appropriate in patients with features suggestive of Lyme disease. Given that Lyme disease is amenable to curative treatment, a larger study is in order to confirm our findings. [Copyright &y& Elsevier]

Background/Aims: The evolution of hepatitis B virus (HBV) serological patterns and the clinical relevance of isolated anti-HBc pattern are not well established in HIV infected patients.Methods: A cohort of 240 patients was followed for 6.9±3.4 years, with iterative HBV serologic assays performed (mean interval of 2.2 years).Results: Five patients without HBV markers at baseline subsequently developed positive anti-HBs (incidence 0.66/100 patient-year), as did two patients with chronic HBs antigenemia (incidence 1.66/100 patient-year). Only one patient with isolated anti-HBc pattern developed HBs chronic antigenemia. Persistent isolated anti-HBc pattern was observed in 37 patients (13 with detectable blood HBV DNA) and was strongly associated with positive hepatitis C virus (HCV) viremia (hazard ratio=9.5, confidence interval 95%: 4.5–20.0, P<0.0001). Hepatic lesions were more severe in HCV infected patients with persistent isolated anti-HBc pattern than in those without (Knodell score 9.2±4.6 versus 6.7±5.0, P=0.04). In time updated analysis, this pattern was not associated with an increased risk of hepatotoxicity, by contrast with HCV infection or positive HBs antigenemia.Conclusions: In HIV infected patients, HBV serological status must be systematically and regularly assessed, and systematic HBV vaccination must be proposed in those without HBV marker. Isolated anti-HBc pattern must be considered in the management of hepatitis C, but not for antiretroviral therapy. [Copyright &y& Elsevier]

Human papillomavirus is a predominant sexually transmitted viral pathogen. Our objective was to analyze the relative distribution of genotypes over time and to determine the genotypes associated with adverse clinical lesions. The study was based on data from adult women with cytological abnormalities from whom histological samples were obtained from 2005 to 2021. HPV genotyping was performed using PCR and INNO-LiPA assay (Fujirebio). Among the 1,017 HPV-positive biopsies, 732 (72%) were infected with a single HPV genotype and 285 (28%) were infected with several HPV genotypes. Most of the infections involved the high-risk genotypes 16, 31, and 52. Throughout the study period, HPV 16 was the most encountered genotype (541, 53.2%), while HPV 18 was rather under-represented (46, 4.5%), especially in invasive cervical carcinoma. HVP52 (165, 16.2%) was detected mainly from 2008 to 2014, and its distribution reached 19.7% in 2011. Such epidemiological data underlines the possibility of an emergence of a high-risk genotype. The most detected low-risk HPV in combination with high-risk HPV was HPV 54 in 6.5% of samples. Monoinfection by HPV 16 led statistically more often to severe lesions than multi-infection involving HPV 16 ( p < 0.001), while for HPV 52, 31 or 33, multi-infections were significantly associated with severe lesions ( p < 0.001 for each of these three genotypes). HPV 16 was involved in 55.2% of high-grade lesions and in situ carcinoma and 76.3% of invasive carcinomas. In severe lesions, HPV 16 participation was predominant, whereas diverse genotypes were seen in low-grade lesions. Importantly, we observed that high-risk genotypes, for example HPV 52, can emerge for a few years then decrease even without vaccine pressure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Auvray, Douvier, Caritey, Bour and Manoha.)

Introduction: Heart transplant (HT) recipients have a high risk of developing severe COVID-19. Immunoglobulin G antibodies are considered to provide protective immunity and T-cell activity is thought to confer protection from severe disease. However, data on T-cell response to mRNA vaccination in a context of HT remains limited., Methods: In 96 HT patients, a IFN-γ release assay and an anti-Spike antibody test were used to evaluate the ability of SARS-CoV-2 mRNA vaccines to generate cellular and humoral immune response. Blood samples were collected few weeks to 7 months after vaccination. Multiple fractional polynomial and LASSO regression models were used to define predictors of T-cell response., Results: Three to five months after vaccination, three doses of vaccine induced a positive SARS-CoV-2 T-cell response in 47% of recipients and a positive humoral response in 83% of recipients, 11.1% of patients remained negative for both T and B cell responses. Three doses were necessary to reach high IgG response levels (>590 BAU/mL), which were obtained in a third of patients. Immunity was greatly amplified in the group who had three vaccine doses plus COVID-19 infection., Conclusion: Our study revealed that T and B immunity decreases over time, leading us to suggest the interest of a booster vaccination at 5 months after the third dose. Moreover, a close follow-up of immune response following vaccination is needed to ensure ongoing immune protection. We also found that significant predictors of higher cellular response were infection and active smoking, regardless of immunosuppressive treatment with mycophenolate mofetil (MMF)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Casenaz, Grosjean, Aho-Glélé, Bour, Auvray and Manoha.)

Goals: The aims of this study were to evaluate whether cytomegalovirus (CMV) infection is associated with hepatocellular carcinoma (HCC) and liver-related mortality in cirrhotic patients., Background: In cirrhotic patients, the determinants of HCC and liver-related death are imperfectly known. CMV infection, by its prooncogenic and proinflammatory properties, may favor both the development of HCC and deleterious systemic inflammation., Study: In the 1178 patients included between June 2008 and December 2012 in the CIrrhose et Risque de Carcinome Hépatocellulaire dans le grand-Est (CIRCE) study, a French multicenter case-control study designed to identify risk factors of HCC among cirrhotic patients, we identified 432 patients with interpretable CMV serological status at baseline. They included 159 cases with HCC and 273 controls. We measured factors associated with HCC at baseline and subsequent HCC in controls, and predictors of overall and liver-related death in the whole study population., Results: During a median follow-up of 31 months, 25 cases of HCC developed in controls, and 209 deaths (163 liver-related) were recorded. There were 247 (57.2%) CMV-seropositive patients. CMV seropositivity was not associated with more frequent HCC at baseline or during follow-up, but among CMV-positive patients with HCC, the proportion of multinodular, infiltrative, or metastatic tumors at diagnosis was higher (73.8% vs. 57.3%; P=0.029), inducing higher mortality (74% vs. 52% at 3 years; P=0.004). By Cox-regression adjusted for age, gender, Model for End-stage Liver Disease (MELD) score, HCC at baseline, and diabetes, CMV seropositivity independently predicted all-cause (hazard ratio=1.45; 95% confidence interval, 1.08-1.94; P=0.013) and liver-related mortality (hazard ratio=1.56; 95% confidence interval, 1.04-2.30; P=0.031)., Conclusions: In this preliminary study, CMV-seropositive cirrhotic patients were at higher risk of liver-related death caused by more aggressive HCCs or severe cirrhosis complications. These findings warrant confirmation.

Aichi virus has been described as a novel causative agent of gastroenteritis in humans. In this study, we report the seroprevalence distribution of Aichi virus in Tunisia. A panel of 1,000 sera was screened by applying an enzyme-linked immunosorbent assay for immunoglobulin G specific for Aichi virus. A considerable prevalence (92%) of antibody to Aichi virus was found across all age groups. The specific anti-Aichi virus antibodies increased with age, from a high rate (68.8%) in children under 10 years old to about 100% in persons more than 60 years old. We found a statistically significant increase in levels of antibody to Aichi virus according to the age of patients. Immunoglobulin M antibodies were detected among five children. A high frequency of Aichi virus monoinfections in hospitalized children with severe gastroenteritis was previously observed in Tunisia. Aichi virus causes diarrhea with dehydration, fever, and vomiting. This work is the first to establish a correlation between the high seroprevalence of specific Aichi virus antibodies, clinical presentation, and a high frequency of isolation of Aichi virus by genomic characterization in stools of children suffering from gastroenteritis. Our data show the importance and emerging character of Aichi virus in the viral etiology of pediatric gastroenteritis.

Objective: To assess cidofovir plasma concentration after intralesional airway administration for recurrent respiratory papillomatosis., Design: Prospective study., Setting: Tertiary care teaching hospital., Patients and Method: The study comprised 21 patients (10 children and 11 adults). Plasma samples were collected at 10 and 45 minutes (T10, T45) or at 10 and 60 minutes (T10, T60) after injection. The measurements of cidofovir were performed using a high-performance liquid chromatographic method., Results: Plasma samples were collected at T10 and T45 on 19 occasions from the children and on 17 from the adults. A linear relationship was found between plasma concentration and dose in children (mean dose 1.2 mg/kg; mean cidofovir plasma levels 0.91 and 0.81 microg/mL) but not in adults (mean dose 0.2 mg/kg; mean plasma levels 0.21 and 0.31 microg/mL). The same relationships were found between dose and area under the concentration/time curve (AUC). Four plasma samples were taken in children at T10 and T60: mean dose 1.2 mg/kg and mean plasma concentrations 1.11 and 1.24 microg/mL. Maximum plasma concentration averaged 34% (SD 11%) in children and 62% (SD 33%) in adults, with equivalent plasma level after intravenous infusion of the same dose., Conclusions: The cidofovir plasma levels were below those leading to toxicity. The levels and the AUC were dose dependent in children but not in adults. Diffusion from the injected site was greatest in a few adults and unpredictable. Because of the great individual variation in diffusion in adults, cidofovir should be used at less than the recommended intravenous dose to prevent any risk of systemic toxicity.