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Plasma proteomics is a precious tool in human disease research but requires extensive sample preparation in order to perform in-depth analysis and biomarker discovery using traditional data-dependent acquisition (DDA). Here, we highlight the efficacy of combining moderate plasma prefractionation and data-independent acquisition (DIA) to significantly improve proteome coverage and depth while remaining cost-efficient. Using human plasma collected from a 20-patient COVID-19 cohort, our method utilizes commonly available solutions for depletion, sample preparation, and fractionation, followed by 3 liquid chromatography-mass spectrometry/MS (LC-MS/MS) injections for a 360 min total DIA run time. We detect 1321 proteins on average per patient and 2031 unique proteins across the cohort. Differential analysis further demonstrates the applicability of this method for plasma proteomic research and clinical biomarker identification, identifying hundreds of differentially abundant proteins at biological concentrations as low as 47 ng/L in human plasma. Data are available via ProteomeXchange with the identifier PXD047901. In summary, this study introduces a streamlined, cost-effective approach to deep plasma proteome analysis, expanding its utility beyond classical research environments and enabling larger-scale multiomics investigations in clinical settings. Our comparative analysis revealed that fractionation, whether the samples were pooled or separate postfractionation, significantly improved the number of proteins quantified. This underscores the value of fractionation in enhancing the depth of plasma proteome analysis, thereby offering a more comprehensive landscape for biomarker discovery in diseases such as COVID-19.
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Ixodes ricinus is a vector of several pathogens of public health interest. While forests are the primary habitat for I. ricinus, its abundance and infection prevalence are expected to vary within forest stands. This study assesses the spatio-temporal variations in tick abundance and infection prevalence with three pathogens in and around a peri-urban forest where human exposure is high. Ticks were sampled multiple times in 2016 and 2018 in multiple locations with a diversity of undergrowth, using the consecutive drags method. Three zoonotic pathogens were screened for, Borrelia burgdorferi s.l., Coxiella burnetii, and Francisella tularensis. The influence of season, type of site and micro-environmental factors on tick abundance were assessed with negative binomial generalized linear mixed-effects models. We collected 1642 nymphs and 181 adult ticks. Ticks were most abundant in the spring, in warmer temperatures, and where undergrowth was higher. Sites with vegetation unaffected by human presence had higher abundance of ticks. Forest undergrowth type and height were significant predictors of the level of tick abundance in a forest. The consecutive drags method is expected to provide more precise estimates of tick abundance, presumably through more varied contacts with foliage. Borrelia burgdorferi s.l. prevalence was estimated from pooled ticks at 5.33%, C. burnetii was detected in six pools and F. tularensis was not detected. Borrelia afzelii was the dominant B. burgdorferi genospecies. Tick abundance and B. burgdorferi s.l. infection prevalence were lower than other estimates in Belgian forests.
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Coxiella burnetii , Bosques , Francisella tularensis , Ixodes , Animales , Bélgica/epidemiología , Ixodes/microbiología , Ixodes/crecimiento & desarrollo , Francisella tularensis/aislamiento & purificación , Coxiella burnetii/aislamiento & purificación , Coxiella burnetii/fisiología , Ninfa/microbiología , Ninfa/crecimiento & desarrollo , Borrelia burgdorferi/aislamiento & purificación , Borrelia burgdorferi/fisiología , Estaciones del Año , Densidad de Población , FemeninoRESUMEN
In-center maintenance hemodialysis (HD) patients are at high risk of acquiring coronavirus disease 2019 (COVID-19) by cross-contamination inside the unit. The aim of this study was to assess retrospectively the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the very first pandemic phase (March-July 2020) in a cohort of in-center maintenance HD patients and in nurses the same HD facility, using a phylogenetic approach. All SARS-CoV-2 quantitative reverse-transcription polymerase chain reaction positive patients and nurses from our HD unit-respectively 10 out of 98, and 8 out of 58- and two other positive patients dialyzed in our self-care unit were included. Whole-genome viral sequencing and phylogenetic analysis supported the cluster investigation. Five positive patients were usually dialyzed in the same room and same shift before their COVID-19 diagnosis was made. Viral sequencing performed on 4/5 patients' swabs showed no phylogenetic link between their viruses. The fifth patient (whose virus could not be sequenced) was dialyzed at the end of the dialysis room and was treated by a different nurse than the one in charge of the other patients. Three nurses shared the same virus detected in both self-care patients (one of them had been transferred to our in-center facility). The epidemiologically strongly suspected intra-unit cluster could be ruled out by viral genome sequencing. The infection control policy did not allow inter-patient contamination within the HD facility, in contrast to evidence of moderate dissemination within the nursing staff and in the satellite unit. Epidemiologic data without phylogenetic confirmation might mislead the interpretation of the dynamics of viral spreading within congregate settings.
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COVID-19/prevención & control , COVID-19/transmisión , Control de Infecciones/métodos , Diálisis Renal , Anciano , Bélgica , COVID-19/epidemiología , Prueba de COVID-19 , Femenino , Genoma Viral , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Filogenia , Estudios Retrospectivos , SARS-CoV-2/genéticaRESUMEN
INTRODUCTION: The COVID-19 pandemic has emerged as a global health problem, associated with high morbidity and mortality rates. The aim of this study was to compare the outcomes of hospitalized patients with COVID-19 or with seasonal influenza in a teaching hospital in Belgium. METHODS: In this retrospective, single-center cohort study, 1384 patients with COVID-19 and 226 patients with influenza were matched using a propensity score with a ratio of 3:1. Primary outcomes included admission to intensive care unit (ICU), intubation rates, hospital length of stay, readmissions within 30 days and in-hospital mortality. Secondary outcomes included pulmonary bacterial superinfection, cardiovascular complications and ECMO. RESULTS: Based on the analysis of the matched sample, patients with influenza had an increased risk of readmission within 30 days (Risk Difference (RD): 0.07, 95% CI: 0.03 to 0.11) and admission to intensive care unit (RD: 0.09, 95% CI: 0.03 to 0.15) compared with those with COVID-19. Patients with influenza had also more pulmonary bacterial superinfections (46.2% vs 7.4%) and more cardiovascular complications (32% vs 3.9%) than patients with COVID-19.However, a two-fold increased risk of mortality (RD: -0.10, 95% CI: 0.15 to -0.05) was observed in COVID-19 compared to influenza. ECMO was also more required among the COVID-19 patients who died than among influenza patients (5% vs 0%). CONCLUSIONS: COVID-19 is associated with a higher in-hospital mortality compared to influenza infection, despite a high rate of ICU admission in the influenza group. These findings highlighted that the severity of hospitalized patients with influenza should not be underestimated.
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COVID-19 , Gripe Humana , Bélgica/epidemiología , COVID-19/epidemiología , Estudios de Cohortes , Mortalidad Hospitalaria , Humanos , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Gripe Humana/terapia , Unidades de Cuidados Intensivos , Pandemias , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
Hepatitis B virus (HBV) genotypes show a distinctive geographical distribution worldwide and genotypes A, D, and E are the most frequently found in Africa. There are only limited studies on HBV genotype distribution in Democratic Republic of Congo (DRC), all done in the western part showing a vast majority of genotype E. In our study, HBV strains from South Kivu, an eastern province of the DRC, were analyzed. Sequencing of 41 serum samples from HBV infected patients revealed strains of genotype A in 40/41 (97.6%) and genotype E in 1/41 (2.4%). The phylogenetic analysis showed that nearly all genotypes A (38/40) were closely related to A1 subgenotype strains found in Rwanda, Haiti, and Martinique while only two strains attached to the A2 subgenotype cluster were isolated. The remaining genotype E case was linked to the western African E crescent. Only the I169T nucleotide substitution was observed in two genotype A samples. In conclusion, the genotype A seems to be the most predominant genotype in eastern DRC with the majority belonging to the Afro-Asian subgenotype (A1). This contrasts with the western part of DRC where genotype E is predominant. These results support the hypothesis of an East-West genotypic demarcation.
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Variación Genética , Genotipo , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B/virología , Filogenia , Adulto , Anciano , República Democrática del Congo/epidemiología , Femenino , Hepatitis B/epidemiología , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
BACKGROUND: As several studies indicated an increase in Lyme disease (LD), notably in neighbouring countries, concerns have arisen regarding the evolution of Lyme disease in Belgium. In order to confirm or infirm the increase of LD in Belgium, we focused on hospital admissions of patients diagnosed with LD between 2000 and 2013 based on hospital admission databases from two hospitals in Belgium. METHODS: Hospital databases are a stable recording system. We did a retrospective analysis of the medical files of patients hospitalized with Lyme disease in two Belgian hospitals between 2000 and 2013. RESULTS: The annual number of cases of LD for the two studied Belgian hospitals remained stable between 2000 and 2013, ranging from 1 for the Cliniques universitaires Saint-Luc to 15 for the the Clinique Saint-Pierre. No increasing trend were noted in the estimated annual incidence rate but the average estimated annual incidence rate was higher for the hospital Saint-Pierre (8.1 ± 3.7 per 100,000 inhabitants) than Saint-Luc (2.2 ± 1.5 per 100,000 inhabitants). The number of hospital cases of LD peaked between June and November. CONCLUSIONS: Based on hospital admissions with LD, no increasing trend was observed for the period 2000-2013 in the two studied Belgian hospitals. This is in line with other studies carried out in Belgium.
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Enfermedad de Lyme/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bélgica/epidemiología , Niño , Preescolar , Bases de Datos Factuales , Femenino , Hospitalización , Hospitales , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenAsunto(s)
Anticuerpos/sangre , Vacunas contra la COVID-19 , COVID-19 , Inmunogenicidad Vacunal/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Anciano de 80 o más Años , Vacuna BNT162 , Bélgica/epidemiología , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Estudios de Cohortes , Femenino , Hogares para Ancianos/estadística & datos numéricos , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/inmunología , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/inmunología , Masculino , Casas de Salud/estadística & datos numéricos , Diálisis Renal/métodos , Diálisis Renal/estadística & datos numéricos , SARS-CoV-2/fisiologíaRESUMEN
UNLABELLED: The role of cell differentiation state on hepatitis B virus (HBV) replication has been well demonstrated, whereas how it determines cell susceptibility to HBV entry is far less understood. We previously showed that umbilical cord matrix stem cells (UCMSC) can be differentiated towards hepatocyte-like cells in vitro. In this study we infected undifferentiated (UD-) and differentiated (D-) UCMSCs with HBV and studied the infection kinetics, comparing them to primary human hepatocytes (PHHs). UD-UCMSCs, although permissive to viral binding, had a very limited uptake capacity, whereas D-UCMSCs showed binding and uptake capabilities similar to PHHs. Likewise, asialoglycoprotein receptor (ASGPR) was up-regulated in UCMSCs upon differentiation. In D-UCMSCs, a dose-dependent inhibition of HBV binding and uptake was observed when ASGPR was saturated with known specific ligands. Subsequent viral replication was shown in D-UCMSCs but not in UD-UCMSCs. Susceptibility of UCMSCs to viral replication correlated with the degree of differentiation. Replication efficiency was low compared to PHHs, but was confirmed by (1) a dose-dependent inhibition by specific antiviral treatment using tenofovir; (2) the increase of viral RNAs along time; (3) de novo synthesis of viral proteins; and (4) secretion of infectious viral progeny. CONCLUSION: UCMSCs become supportive of the entire HBV life cycle upon in vitro hepatic differentiation. Despite low replication efficiency, D-UCMSCs proved to be fully capable of HBV uptake. Overall, UCMSCs are a unique human, easily available, nontransformed, in vitro model of HBV infection that could prove useful to study early infection events and the role of the cell differentiation state on such events.
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Células Madre Fetales/fisiología , Virus de la Hepatitis B/fisiología , Hepatocitos/virología , Interacciones Huésped-Patógeno , Modelos Biológicos , Receptor de Asialoglicoproteína/metabolismo , Diferenciación Celular , Células Cultivadas , Células Madre Fetales/virología , Genes Virales , Hepatocitos/citología , Humanos , Cordón Umbilical/citología , Proteínas Virales/biosíntesis , Replicación ViralRESUMEN
BACKGROUND: Occult hepatitis B infection (OBI) is a globally prevalent infection, with its frequency being influenced by the prevalence of hepatitis B virus (HBV) infection in a particular geographic region, including Africa. OBI can be transmitted through blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma (HCC). The associated HBV genotype influences the infection. AIM: To highlight the genetic diversity and prevalence of OBI in Africa. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed, Google Scholar, Science Direct, and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa. RESULTS: The synthesis included 83 articles, revealing that the prevalence of OBI varied between countries and population groups, with the highest prevalence being 90.9% in patients with hepatitis C virus infection and 38% in blood donors, indicating an increased risk of HBV transmission through blood transfusions. Cases of OBI reactivation have been reported following chemotherapy. Genotype D is the predominant, followed by genotypes A and E. CONCLUSION: This review highlights the prevalence of OBI in Africa, which varies across countries and population groups. The study also demonstrates that genotype D is the most prevalent.
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Introduction: A hypothetical risk of SARS-CoV-2 airborne transmission through nebulization was suggested based on a potential environmental contamination by the fugitive aerosol emitted in the environment during the procedure. The aim of this study was to verify this risk from the fugitive aerosol emitted by COVID-19 patients during one nebulization session. Methods: In this cohort study, COVID-19 patients treated with nebulization were recruited at their admission to the hospital. Patients had to perform a nebulization session while a BioSampler® and a pump were used to vacuum the fugitive aerosol and collect it for SARS-CoV-2 RNA detection. Results: Ten consecutive patients hospitalized with COVID-19 were recruited. The median viral load was 6.5 × 106 copies/mL. Two out of the 10 samples from the fugitive aerosol collected were positive to SARS-CoV-2. Conclusion: The risk of fugitive aerosol contamination with SARS-CoV-2 during nebulization has now been verified.
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COVID-19 , Humanos , SARS-CoV-2 , ARN Viral , Estudios de Cohortes , Administración por Inhalación , Aerosoles y Gotitas RespiratoriasRESUMEN
Introduction: The efficacy of nirmatrelvir-ritonavir (NR; Paxlovid, Pfizer, New York, NY) to decrease the risk of progression to severe COVID-19 in high-risk patients has been demonstrated. However, evidence in infected kidney transplant recipients (KTRs) is lacking. Moreover, NR has significant and potentially harmful interactions with calcineurin inhibitors (CNIs). Methods: In this single-center retrospective study, we included all KTRs treated with NR from April 28 to June 3, 2022. A standard management strategy of CNI dose adaptation (discontinuation of tacrolimus 12 hours before the start of NR and administration of 20% of the cyclosporine dose) and laboratory follow-up was applied. Results: A total of 14 patients were included. Compared with day-0 (day before NR initiation), day-7 plasma creatinine concentrations and SARS-CoV-2 viral loads were similar (P = 0.866) and decreased (P = 0.002), respectively. CNI trough concentrations at the end of the treatment were satisfactory, nonetheless, with high individual variability. After a median follow-up time of 34 days, no death or viral pneumonia were observed. Nevertheless, 2 patients experienced early SARS-CoV-2 infection relapses (at day-10 and day-21) associated with an increase in SARS-CoV-2 viral loads. Conclusion: NR can be used in KTRs but requires a strict protocol of drug adaptation. We observed 2 cases of early relapse after NR treatment that need further investigations.
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Rationale & Objective: Neutralizing monoclonal antibody treatments have shown promising preliminary results in kidney transplant recipients infected with severe acute respiratory syndrome coronavirus 2. However, their efficacy in kidney transplant recipients infected with the Omicron variant has not been reported yet. Study Design: Single-center retrospective study. Setting & Participants: We included all consecutive kidney transplant recipients treated with monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 infections (positive polymerase chain reaction on nasopharyngeal swab) between June 10, 2021, and January 14, 2022. Forty-seven kidney transplant recipients were included. All patients had symptoms evolving for ≤7 days and no oxygen therapy need at monoclonal antibody infusion. Results: Symptoms at diagnosis were mainly cough (n = 25; 53%) and fever (n = 15; 32%). Eighty-three percent of the cohort (n = 39) had been vaccinated with at least 2 doses before infection, of whom 30 (77%) had demonstrated a vaccine-induced humoral response. They were treated with either casirivimab-imdevimab (n = 16; 34%) or sotrovimab (n = 31; 66%) a median of 2 days (range, 0-6 days) after the onset of symptoms. Except for 1 mild allergic reaction during casirivimab-imdevimab infusion, no side effects were reported. The median viral loads at admission (day 0) and 7 days after monoclonal antibody infusion were 2,110,027 copies/mL (range, 1,000-153,798,962 copies/mL) and 1,000 copies/mL (range, 0-10,000,000 copies/mL), respectively. Genotypes were available for 22 kidney transplant recipients (47%). Omicron, Delta, and Gamma variants were identified in 13 (59%), 8 (36%), and 1 (5%) patients, respectively. In kidney transplant recipients infected with the Omicron variant, the median viral loads at day 0 and day 7 were 752,789 copies/mL (range, 4,000-12,859,300 copies/mL) and 1,353 copies/mL (range, 0-1,211,163 copies/mL), respectively. 2 kidney transplant recipients required hospitalization immediately after sotrovimab perfusion for oxygen therapy that was weaned in 3 days, allowing patients' discharge. None were admitted to the intensive care unit or died. Limitations: Small sample size, no control group. Conclusions: Neutralizing monoclonal antibody therapy is associated with positive outcomes in kidney transplant recipients with mild coronavirus disease 2019, including those infected with the Omicron variant.
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Schools have been a point of attention during the pandemic, and their closure one of the mitigating measures taken. A better understanding of the dynamics of the transmission of SARS-CoV-2 in elementary education is essential to advise decisionmakers. We conducted an uncontrolled non-interventional prospective study in Belgian French-speaking schools to describe the role of attending asymptomatic children and school staff in the spread of COVID-19 and to estimate the transmission to others. Each participant from selected schools was tested for SARS-CoV-2 using a polymerase chain reaction (PCR) analysis on saliva sample, on a weekly basis, during six consecutive visits. In accordance with recommendations in force at the time, symptomatic individuals were excluded from school, but per the study protocol, being that participants were blinded to PCR results, asymptomatic participants were maintained at school. Among 11 selected schools, 932 pupils and 242 school staff were included between January and May 2021. Overall, 6449 saliva samples were collected, of which 44 came back positive. Most positive samples came from isolated cases. We observed that asymptomatic positive children remaining at school did not lead to increasing numbers of cases or clusters. However, we conducted our study during a period of low prevalence in Belgium. It would be interesting to conduct the same analysis during a high prevalence period.
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COVID-19 , SARS-CoV-2 , Niño , Humanos , SARS-CoV-2/genética , Proyectos Piloto , Bélgica/epidemiología , COVID-19/epidemiología , Estudios Prospectivos , Instituciones AcadémicasRESUMEN
More than two years on, the COVID-19 pandemic continues to wreak havoc around the world and has battle-tested the pandemic-situation responses of all major global governments. Two key areas of investigation that are still unclear are: the molecular mechanisms that lead to heterogenic patient outcomes, and the causes of Post COVID condition (AKA Long-COVID). In this paper, we introduce the HYGIEIA project, designed to respond to the enormous challenges of the COVID-19 pandemic through a multi-omic approach supported by network medicine. It is hoped that in addition to investigating COVID-19, the logistics deployed within this project will be applicable to other infectious agents, pandemic-type situations, and also other complex, non-infectious diseases. Here, we first look at previous research into COVID-19 in the context of the proteome, metabolome, transcriptome, microbiome, host genome, and viral genome. We then discuss a proposed methodology for a large-scale multi-omic longitudinal study to investigate the aforementioned biological strata through high-throughput sequencing (HTS) and mass-spectrometry (MS) technologies. Lastly, we discuss how a network medicine approach can be used to analyze the data and make meaningful discoveries, with the final aim being the translation of these discoveries into the clinics to improve patient care.
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COVID-19 , Enfermedades Transmisibles , COVID-19/complicaciones , COVID-19/epidemiología , Enfermedades Transmisibles/epidemiología , Humanos , Estudios Longitudinales , Metabolómica/métodos , Pandemias , Biología de Sistemas/métodos , Síndrome Post Agudo de COVID-19RESUMEN
Rapid diagnostic tests (RDTs) are widely used in Lubumbashi for the diagnosis of viral hepatitis B and C. To date, there are no works that have been carried out in Lubumbashi to independently assess the performance of such tests. This study aimed at assessing the effectiveness of RDTs for the detection of HBsAg and anti-HCV antibodies in order to identify infected blood donors in Lubumbashi. A total of 300 serum samples (100 HBsAg positive samples; 100 anti-HCV positive samples and 100 HBsAg and anti-HCV negative samples) were tested simultaneously using the 6 locally used RDTs and as gold standard the chemiluminescent assays for HBsAg and the RT-TMA for HCV detection. The six evaluated RDTs demonstrated a sensitivity and a negative predictive value (NPV) of 100 % whereas the specificity and positive predictive value (PPV) varied from 46 % to 98.1 %. SB BioLine HBsAg test performed best in this study with 100 % of sensitivity, 97.1 % of specificity, 100 % of NPV and 96.9 % of PPV. Furthermore, sensitivity, specificity, NPV and PPV for SB BioLine HCV test were as follows: 100 %, 98.1 %, 100 % and 93.9 %. Therefore, SD BioLine tests (HBsAg, HCV) would be selected as the first line RDTs for the detection and the diagnostic of hepatitis B and C. They can prevent blood-borne transmission of HBV and HCV in areas with limited incomes as Lubumbashi.
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Donantes de Sangre , Pruebas Diagnósticas de Rutina , Anticuerpos contra la Hepatitis B/sangre , Hepatitis B/diagnóstico , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/diagnóstico , República Democrática del Congo , Hepacivirus/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Humanos , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: Several SARS-CoV-2 immunoassays have been developed recently. The purpose of this study was to assess the performance of five immunoassays for the detection of SARS-CoV-2 antibodies. METHODS: Two quantitative automated immunoassays (Maglumi™2019-n-Cov IgG and IgM and Euroimmun Anti-SARS-CoV-2 IgG and IgA assays) and three lateral flow rapid tests were performed. This retrospective study included 200 residual sera from patients and healthy volunteers. Case serum samples (n = 128) were obtained from COVID-19 patients confirmed by RT-qPCR and CT-scan. Days since onset of symptoms was collected from their medical records. Control non-SARS-CoV-2 samples (n = 72) were obtained from anonymous stored residual serum samples. RESULTS: Maglumi™ IgG/IgM tests showed overall less sensitivity than Euroimmun IgG/IgA test (84.4 % versus 64.3 %). Both tests showed similar specificities of IgG at 99 % and 100 %, respectively. The results from the lateral flow assays were easily interpretable with unambiguous coloured reading bands. The overall sensitivity of the three tests was similar (around 70 %) without any significant differences. The sensitivity of the three lateral flow assays and also of the serological quantitative assays increased during the second week after symptom onset and all reached similar values (91 %-94 %) after 14 days. CONCLUSION: This study shows accurate and equivalent performance of the five serological antibody assays (ELISA, CLIA and three lateral flow tests) in detecting SARS-CoV-2 antibodies 14 days after the onset of COVID-19 symptoms. This is compatible with their application in specific clinical contexts and in determining epidemiological strategies for the COVID-19 pandemic.
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Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Infecciones por Coronavirus/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Pandemias , Neumonía Viral/diagnóstico , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/virología , Humanos , Inmunoensayo/métodos , Neumonía Viral/virología , Estudios Retrospectivos , SARS-CoV-2 , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection. Although previous studies have reported positive results with DAAs after kidney transplantation (KT), their impact on the prevalence of HCV viremia (HCVv) in prevalent kidney transplant recipients (KTRs) remains ill defined. METHODS: We retrospectively reviewed the HCV status of all patients followed at Cliniques Universitaires Saint-Luc, Brussels, Belgium, outpatient KT clinic between January 2014 and December 2018. We collected the clinical features of KTRs treated with DAAs during this period and calculated the annual prevalence of HCVv over this period. RESULTS: Out of 1451 KTRs, 22 (1.52%) had HCVv in 2014 to 2018. From 2014 to 2018, the annual prevalence of HCVv dropped from 1.97% to 0.43%, (P < .001). Fourteen KTRs were treated with DAAs a median of 197 months (range: 5-374) after KT, mostly (79%) in 2017 after reimbursement restrictions of DAAs for KTRs in Belgium were removed. DAA treatment was safe with a sustained virological response rate at 12 weeks after treatment (SVR12) of 93%. Two patients died 14 months (lymphoma, despite SVR12) and 7 months (hepatocarcinoma, no SVR12) after DAAs initiation, respectively. Among HCVv KTRs not treated with DAAs (n = 8), 2 lost their graft, 5 died, and 1 is initiating therapy. The current prevalence of HCVv in the cohort is 0.08%, with a single patient currently on treatment. CONCLUSION: Treatment with DAAs led to a dramatic decrease of HCVv prevalence in this KTR cohort. DAA use was safe and effective. Elimination of HCV is possible at KT clinics.
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Antivirales/uso terapéutico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/tratamiento farmacológico , Viremia/tratamiento farmacológico , Adulto , Bélgica/epidemiología , Estudios de Cohortes , Femenino , Hepatitis C/etiología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/virología , Prevalencia , Estudios Retrospectivos , Respuesta Virológica Sostenida , Resultado del Tratamiento , Viremia/etiologíaRESUMEN
INTRODUCTION: We aim to report on results and challenges of different methods used for hepatitis C (HCV) genotyping in a Cambodian HCV/HIV coinfection project. METHODS: Samples of 106 patients were available. HCV genotyping was initially (63 samples) done by the LightPower Taqman real-time PCR method (Viet A Corp.) and quality controlled using the Versant 2.0 line probe assay (Siemens Healthcare). Next, following interim quality control results, all 106 samples were (re)genotyped with Versant 2.0, complemented with 5'UTR/core sequencing for uninterpretable/incomplete Versant results. RESULTS: Using Versant, 103 (97.2%) of the 106 HCV-coinfected patients had an interpretable genotype result: 1b (50.5%), 6 non-a/non-b (30.1%), 1a (6.8%), 6a or b (4.9%), 2 (3.9%), 1 (2.9%) and 3 (1.0%). For 16 samples that were interpreted as genotype 1 or 1b per Versant's current instructions, it could not be excluded that it concerned a genotype 6 infection as the core region line patterns on the Versant test strip were unavailable, inconclusive or atypical. Upon sequencing, seven of these were genotyped as 1b and nine as genotype 6. Combining Versant and sequencing results, a definitive genotype was assigned in 104 patients: 1b (44.2%), 6 non-a/non-b (39.4%), 1a (6.7%), 6a or b (4.8%), 2 (3.8%) and 3 (1.0%). Genotyping by LightPower and Versant was discordant for 23 (of 63) samples. The LightPower assay misclassified all genotype 6 non-a/non-b samples as genotype 1, which indicates that this assay is only using 5'UTR information. CONCLUSIONS: HCV genotype 1b and genotype 6 non-a/non-b were most common. With Versant 2.0 (using 5'UTR and core information), genotype classification (1 or 6) remained inconclusive in 15% of samples. The locally available method (LightPower assay) failed to identify genotype 6 non-a/non-b, which highlights that methods using 5'UTR information only should not be used in Cambodia. Regional/national guidelines should be explicit about this. TRIAL REGISTRATION: This study was performed as part of a larger cross-sectional study on the burden of hepatitis C coinfection in HIV patients in Cambodia (Clinical.trials.gov: HCV-Epi NCT02361541).
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RATIONALE & OBJECTIVE: The world is facing a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although kidney transplant recipients are at increased risk for viral infections, the impact of their chronic immunosuppressed status on the risk for acquiring coronavirus disease 2019 (COVID-19) and disease severity is unknown. STUDY DESIGN: All cases of COVID-19 infection in our cohort of kidney transplant recipients were prospectively monitored. Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients. SETTING & PARTICIPANTS: 22 COVID-19 infections were diagnosed in our cohort of 1,200 kidney transplant recipients. RESULTS: Most common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n = 3), moderate (n = 8), extensive (n = 1), severe (n = 2), and critical (n = 1) involvement. Immunosuppression reduction was initiated in all patients. Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died. LIMITATIONS: Small sample size and short follow-up. CONCLUSIONS: The clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.