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We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1019 treatment-naive persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90â kg and 0.98â kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH.
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Índice de Masa Corporal , ADN Mitocondrial , Infecciones por VIH , Haplotipos , Aumento de Peso , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Aumento de Peso/efectos de los fármacos , Aumento de Peso/genética , Masculino , Femenino , Adulto , ADN Mitocondrial/genética , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Mitocondrias/genética , Mitocondrias/efectos de los fármacos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.
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Hepatitis C virus (HCV) core antigen (HCVcAg) assay is an alternative for diagnosing HCV infection in a single step. This meta-analysis aimed to evaluate the Abbott ARCHITECT HCV Ag assay's diagnostic performance (validity and utility) for diagnosing active hepatitis C. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched until 10 January 2023. The protocol was registered at the prospective international register of systematic reviews (PROSPERO: CRD42022337191). Abbott ARCHITECT HCV Ag assay was the test for evaluation, and nucleic acid amplification tests with a cut-off ≤50 IU/mL were the gold standard. Statistical analysis was performed using STATA with the MIDAS module and random-effects models. The bivariate analysis was conducted on 46 studies (18,116 samples). The pooled sensitivity was 0.96 (95% CI = 0.94-0.97), specificity 0.99 (95% CI = 0.99-1.00), positive likelihood ratio 141.81 (95% CI = 72.39-277.79), and negative likelihood ratio 0.04 (95% CI = 0.03-0.06). The area under the summary receiver operating characteristic curve was 1.00 (95% CI = 0.34-1.00). For active hepatitis C prevalence values of 0.1%-15%, the probability that a positive test was a true positive was 12%-96%, respectively, indicating that a confirmatory test should be necessary, particularly with a prevalence ≤5%. However, the probability that a negative test was a false negative was close to zero, indicating the absence of HCV infection. The validity (accuracy) of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection in serum/plasma samples was excellent. Although the HCVcAg assay showed limited diagnostic utility in low prevalence settings (≤1%), it might help diagnose hepatitis C in high prevalence scenarios (≥5%).
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Antígenos de la Hepatitis C , Hepatitis C , Humanos , Antígenos de la Hepatitis C/análisis , Sensibilidad y Especificidad , Estudios Prospectivos , ARN Viral , Hepacivirus/genéticaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.
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COVID-19 , Unidades de Cuidados Intensivos , Tiempo de Internación , Respiración Artificial , Acortamiento del Telómero , Humanos , Masculino , COVID-19/terapia , COVID-19/complicaciones , Femenino , Persona de Mediana Edad , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Acortamiento del Telómero/fisiología , Tiempo de Internación/estadística & datos numéricos , Anciano , Estudios Longitudinales , SARS-CoV-2RESUMEN
BackgroundPeople who use drugs (PWUD) are a key target population to reduce the burden of hepatitis C virus (HCV) infection.AimTo assess risk factors and temporal trends of active HCV infection in PWUD in Madrid, Spain.MethodsWe conducted a retrospective study between 2017 and 2023, including 2,264 PWUD visiting a mobile screening unit. Data about epidemiology, substance use and sexual risk behaviour were obtained through a 92-item questionnaire. HCV was detected by antibody test, followed by RNA test. The primary outcome variable was active HCV infection prevalence, calculated considering all individuals who underwent RNA testing and analysed by logistic regression adjusted by the main risk factors.ResultsOf all participants, 685 tested positive for anti-HCV antibodies, and 605 underwent RNA testing; 314 had active HCV infection, and 218 initiated treatment. People who inject drugs (PWID) were identified as the main risk group. The active HCV infection rate showed a significant downward trend between 2017 and 2023 in the entire study population (23.4% to 6.0%), among PWID (41.0% to 15.0%) and PWUD without injecting drug use (7.0% to 1.3%) (p < 0.001 for all). These downward trends were confirmed by adjusted logistic regression for the entire study population (adjusted odds ratio (aOR): 0.78), PWID (aOR: 0.78), and PWUD non-IDU (aOR: 0.78).ConclusionsOur study demonstrates a significant reduction in active HCV infection prevalence among PWUD, particularly in PWID, which suggests that efforts in the prevention and treatment of HCV in Madrid, Spain, have had an impact on the control of HCV infection.
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Hepacivirus , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , España/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Hepatitis C/epidemiología , Adulto , Prevalencia , Persona de Mediana Edad , Abuso de Sustancias por Vía Intravenosa/epidemiología , Factores de Riesgo , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Consumidores de Drogas/estadística & datos numéricos , Asunción de Riesgos , Anticuerpos contra la Hepatitis C/sangre , Trastornos Relacionados con Sustancias/epidemiología , Conducta Sexual/estadística & datos numéricos , Adulto Joven , Encuestas y CuestionariosRESUMEN
In this case-control study, we evaluated the association between serum antibodies against hepatitis E virus (HEV) and central nervous system (CNS) neurodegenerative disorders (NDs) in older people with dementia. The presence of anti-HEV antibodies was related to a higher adjusted odds ratio (aOR) of having CNS NDs by neuropathological diagnosis (aOR, 2.13; P = .007) and clinical/neuropathological diagnosis (1.84; P = .02). Besides, serum anti-HEV antibodies were directly related to neuropathological injury (higher vascular pathology [aOR, 1.97; P = .006]) and higher probability of Alzheimer-type pathology (1.84; P = .02). In conclusion, the presence of anti-HEV antibodies was related to higher odds of CNS NDs and neuropathological injury in older people.
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Demencia , Virus de la Hepatitis E , Hepatitis E , Enfermedades Neurodegenerativas , Humanos , Anciano , Hepatitis E/complicaciones , Hepatitis E/epidemiología , Estudios Seroepidemiológicos , Estudios de Casos y Controles , Anticuerpos Antihepatitis , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/complicaciones , Demencia/epidemiología , Demencia/complicaciones , Inmunoglobulina MRESUMEN
BACKGROUND: We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). METHODS: Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. RESULTS: A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). CONCLUSIONS: Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.
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Infecciones por VIH , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Masculino , Estudio de Asociación del Genoma Completo , Obesidad/complicaciones , Aumento de Peso/genética , Infecciones por VIH/complicaciones , Antirretrovirales/uso terapéuticoRESUMEN
The standard algorithm for diagnosing hepatitis C virus (HCV) infection has two steps, an HCV antibody test for screening and a nucleic acid amplification test (NAAT) for confirmation. However, the HCV core antigen (HCVcAg) detection assay is an alternative for one-step diagnosis. We aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay to detect active hepatitis C in serum/plasma in people living with HIV/AIDS (PLWHA), through a systematic review and meta-analysis. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched until 20 September 2022 (PROSPERO, CRD42022348351). We included studies evaluating Abbott ARCHITECT HCV Ag assay (index assay) versus NAATs (reference test) in PLWHA coinfected with HCV who did not receive antiviral treatment for HCV. Meta-analysis was performed with the MIDAS module using Stata and random-effects models. The QUADAS-2 tool evaluated the risk of bias. The bivariate analysis was conducted on 11 studies with 2,407 samples. Pooled sensitivity was 0.95 (95% CI = 0.92 to 0.97), specificity 0.97 (95% CI = 0.93 to 0.99), positive likelihood ratio 37.76 (95% CI = 12.84 to 111.02), and negative likelihood ratio 0.06 (95% CI = 0.04 to 0.09). The area under the curve was 0.97 (95% CI = 0.20 to 1.00). For low prevalence (≤5%), the posttest probability that an individual with a positive test was a true positive ranged from 4% to 67%, whereas, at high prevalence (≥10%), the posttest probability was between 81% and 87%, indicating that a confirmatory test should be necessary, particularly with prevalence values of ≤1%. Regardless of prevalence, the probability that an individual with a negative test was a false negative was close to zero, indicating that the individual was not infected with HCV. In conclusion, the accuracy of the Abbott ARCHITECT HCV Ag assay was very good for HCV screening in serum/plasma samples from PLWHA. The clinical utility to confirm HCV infection was acceptable in high-prevalence settings (≥10%) but poor in low-prevalence settings (≤1%). Furthermore, it was excellent in excluding active HCV infection.
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Infecciones por VIH , Hepatitis C , Humanos , Hepacivirus/genética , Sensibilidad y Especificidad , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Tamizaje Masivo , Antígenos de la Hepatitis C , Infecciones por VIH/complicacionesRESUMEN
IRF5-TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)-1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïve with CD4+ ≥ 500 cells/mm3 , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5-TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5-TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5-TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.
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Infecciones por VIH , Humanos , Estudios Retrospectivos , Polimorfismo de Nucleótido Simple , Factores Reguladores del Interferón/genética , Genotipo , Predisposición Genética a la Enfermedad , beta Carioferinas/genéticaRESUMEN
Increasing age is associated with severity and higher mortality of COVID-19. Telomere shortening is associated with higher risk of infections and may be used to identify those patients who are more likely to die. We evaluated the association between relative telomere length (RTL) and COVID-19 mortality. RTL was measured in patients hospitalized because of COVID-19. We used Kaplan-Meier method to analyze survival probabilities, and Cox regression to investigate the association between RTL and mortality (30 and 90 days). Six hundred and eight patients were included in the analysis (mean age =72.5 years, 41.1% women, and 53.8% Caucasic). During the study period, 75 people died from COVID-19 and 533 survived. Lower RTL was associated with a higher risk of death in women either at 30 (adjusted hazard ratio [HR] (aHR) = 3.33; 95% confidence interval [CI] = 1.05-10.00; p = 0.040) and at 90 days (aHR = 3.57; 95%CI = 1.23-11.11; p = 0.019). Lower RTL was associated with a higher risk of dying of COVID-19 in women. This finding suggests that RTL has an essential role in the prognosis of this subset of the population.
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COVID-19 , Caracteres Sexuales , Humanos , Masculino , Femenino , Anciano , Pronóstico , Acortamiento del Telómero , TelómeroRESUMEN
Interleukin 7 receptor (IL7R) is vital in the adaptive immune response against human immunodeficiency viruses (HIV). We assessed IL7RA polymorphisms (SNPs) in antiretroviral therapy (ART)-naïve HIV patients for their association with spontaneous HIV infection control. We conducted a retrospective cohort study involving 667 ART-naïve patients categorized by HIV progression (ordinal variable): 150 rapid progressors, 334 moderate/typical progressors, 86 long-term nonprogressors elite controllers (LTNPs-EC), and 97 LTNPs-non-EC. We genotyped three IL7RA SNPs using Agena Bioscience's MassARRAY platform. The association between IL7RA SNPs and spontaneous HIV infection control was evaluated using ordinal logistic regression. Individuals carrying the rs10491434 G allele have a higher likelihood of spontaneous HIV infection control (adjusted odds ratio [aOR] = 1.33; p = 0.023). Moreover, the IL7RA GCT haplotype, consisting of three specific SNPs (rs6897932, rs987106, and rs10491434), demonstrated an association with the control of untreated HIV infection (aOR = 1.34; p = 0.050). Remarkably, the rs10491434 SNP and the IL7RA GCT haplotype exhibited similar aOR values, suggesting that rs10491434 may be primarily responsible for the observed effect of the haplotype. IL7RA rs10491434 G allele is associated with a higher likelihood of spontaneous HIV infection control, indicating its significant role in the pathogenesis of HIV, possibly influencing infection course and viral replication control.
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Infecciones por VIH , Subunidad alfa del Receptor de Interleucina-7 , Humanos , Progresión de la Enfermedad , Infecciones por VIH/genética , Infecciones por VIH/terapia , Control de Infecciones , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Subunidad alfa del Receptor de Interleucina-7/genéticaRESUMEN
PURPOSE: We aimed to assess IgG antibodies against the SARS-CoV-2 spike protein (anti-SARS-CoV-2 S IgG) in vaccinated mothers and their infants at delivery and 2-3 months of age. METHODS: We conducted a prospective study on mothers who received at least one dose of the COVID-19 vaccine (Pfizer-BNT162b2, Moderna mRNA-1273, or Oxford-AstraZeneca ChAdOx1-S) during pregnancy and on their infants. The baseline was at the time of delivery (n = 93), and the end of follow-up was 2 to 3 months post-partum (n = 53). Serum anti-SARS-CoV-2 S IgG titers and ACE2 binding inhibition levels were quantified by immunoassays. RESULTS: Mothers and infants had high anti-SARS-CoV-2 S IgG titers against the B.1 lineage at birth. However, while antibody titers were maintained at 2-3 months post-partum in mothers, they decreased significantly in infants (p < 0.001). Positive and significant correlations were found between anti-SARS-CoV-2 S IgG titers and ACE2-binding inhibition levels in mothers and infants at birth and 2-3 months post-partum (r > 0.8, p < 0.001). Anti-S antibodies were also quantified for the Omicron variant at 2-3 months post-partum. The antibody titers against Omicron were significantly lower in mothers and infants than those against B.1 (p < 0.001). Again, a positive correlation was observed for Omicron between IgG titers and ACE2-binding inhibition both in mothers (r = 0.818, p < 0.001) and infants (r = 0.386, p < 0.005). Previous SARS-CoV-2 infection and COVID-19 vaccination near delivery positively impacted anti-SARS-CoV-2 S IgG levels. CONCLUSIONS: COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.
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OBJECTIVE: This study analyzed, at a postcode detailed level, the relation-ship between short-term exposure to environmental factors and hospital ad-missions, in-hospital mortality, ICU admission, and ICU mortality due to COVID-19 during the lockdown and post-lockdown 2020 period in Spain. METHODS: We performed a nationwide population-based retrospective study on 208,744 patients admitted to Spanish hospitals due to COVID-19 based on the Minimum Basic Data Set (MBDS) during the first two waves of the pandemic in 2020. Environmental data were obtained from Copernicus Atmosphere Monitoring Service. The association was assessed by a generalized additive model. RESULTS: PM2.5 was the most critical environmental factor related to hospital admissions and hospital mortality due to COVID-19 during the lockdown in Spain, PM10, NO2, and SO2and also showed associations. The effect was considerably reduced during the post-lockdown period. ICU admissions in COVID-19 patients were mainly associated with PM2.5, PM10, NO2, and SO2 during the lockdown as well. During the lockdown, exposure to PM2.5 and PM10 were the most critical environmental factors related to ICU mortality in COVID-19. CONCLUSION: Short-term exposure to air pollutants impacts COVID-19 out-comes during the lockdown, especially PM2.5, PM10, NO2, and SO2. These pollutants are associated with hospital admission, hospital mortality and ICU admission, while ICU mortality is mainly associated with PM2.5 and PM10. Our findings reveal the importance of monitoring air pollutants in respiratory infectious diseases.
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Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Humanos , COVID-19/epidemiología , Contaminación del Aire/análisis , Dióxido de Nitrógeno/análisis , Estudios Retrospectivos , Control de Enfermedades Transmisibles , Contaminantes Atmosféricos/análisis , Hospitales , Material Particulado/análisis , Monitoreo del AmbienteRESUMEN
BACKGROUND: About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group). METHODS: We performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log-link) adjusted by significant variables and sex. RESULTS: 13 ICs (BTLA, CD137(4-1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, and TIM-3) and 13 SASP proteins (EGF, Eotaxin, IL-1alpha, IL-1RA, IL-8, IL-13, IL-18, IP-10, SDF-1alpha, HGF, beta-NGF, PLGF-1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After stratifying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD-L2 was significantly higher in SC women, and no differences in SASP were found. CONCLUSIONS: Higher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non-hepatic diseases.
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INTRODUCTION: Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later. METHODS: We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples. RESULTS: At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P < 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P < 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (R2 = 0.203; P < 0.001), cord sera (R2 = 0.378; P < 0.001), and milk (R2 = 0.564; P < 0.001), and at six months in maternal sera (R2 = 0.600; P < 0.001). CONCLUSIONS: High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.
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COVID-19 , Complicaciones Infecciosas del Embarazo , Recién Nacido , Embarazo , Femenino , Niño , Humanos , Madres , Glicoproteína de la Espiga del Coronavirus , Enzima Convertidora de Angiotensina 2 , Estudios Prospectivos , SARS-CoV-2 , Inmunoglobulina A , Inmunoglobulina G , Inmunoglobulina MRESUMEN
Mucosal immune response in the upper respiratory tract is crucial for initial control of viral replication, clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and progression of coronavirus disease 2019 (COVID-19). We analyzed SARS-CoV-2 RNA load and expression of selected immune genes in the upper respiratory tract (nasopharynx) of 255 SARS-CoV-2-infected patients and evaluated their association with severe COVID-19. SARS-CoV-2 replication in nasopharyngeal mucosa induces expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with intensive care unit admission or death, although CCL5 was the best predictor of COVID-19 severity.
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COVID-19 , Quimiocina CCL5/genética , Nasofaringe/virología , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/mortalidad , Quimiocina CCL5/metabolismo , Humanos , Unidades de Cuidados Intensivos , ARN Viral/genética , Índice de Severidad de la Enfermedad , Carga ViralRESUMEN
BACKGROUND: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. PATIENTS/METHODS: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. RESULTS: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). CONCLUSIONS: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.
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Anticuerpos Antivirales/sangre , Antígenos Virales/sangre , COVID-19 , COVID-19/inmunología , COVID-19/mortalidad , Enfermedad Crítica , Humanos , ARN Viral/sangre , SARS-CoV-2RESUMEN
BACKGROUND: Patients with a significant decrease in hepatic venous pressure gradient (HVPG) have a considerable reduction of liver complications and higher survival after HCV eradication. OBJECTIVES: To evaluate the association between the baseline blood microbiome and the changes in HVPG after successful direct-acting antiviral (DAA) therapy in patients with HCV-related cirrhosis. METHODS: We performed a prospective study in 32 cirrhotic patients (21 HIV positive) with clinically significant portal hypertension (HVPG ≥10 mmHg). Patients were assessed at baseline and 48 weeks after HCV treatment completion. The clinical endpoint was a decrease in HVPG of ≥20% or HVPG <12 mmHg at the end of follow-up. Bacterial 16S ribosomal DNA was sequenced using MiSeq Illumina technology, inflammatory plasma biomarkers were investigated using ProcartaPlex immunoassays and the metabolome was investigated using GC-MS. RESULTS: During the follow-up, 47% of patients reached the clinical endpoint. At baseline, those patients had a higher relative abundance of Corynebacteriales and Diplorickettsiales order, Diplorickettsiaceae family, Corynebacterium and Aquicella genus and Undibacterium parvum species organisms and a lower relative abundance of Oceanospirillales and Rhodospirillales order, Halomonadaceae family and Massilia genus organisms compared with those who did not achieve the clinical endpoint according to the LEfSe algorithm. Corynebacteriales and Massilia were consistently found within the 10 bacterial taxa with the highest differential abundance between groups. Additionally, the relative abundance of the Corynebacteriales order was inversely correlated with IFN-γ, IL-17A and TNF-α levels and the Massilia genus with glycerol and lauric acid. CONCLUSIONS: Baseline-specific bacterial taxa are related to an HVPG decrease in patients with HCV-related cirrhosis after successful DAA therapy.
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Hepatitis C Crónica , Hipertensión Portal , Microbiota , Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/etiología , Cirrosis Hepática/complicaciones , Estudios ProspectivosRESUMEN
The human respiratory syncytial virus (HRSV) causes severe lower respiratory tract infections in infants and the elderly. An exuberant inadequate immune response is behind most of the pathology caused by the HRSV. The main targets of HRSV infection are the epithelial cells of the respiratory tract, where the immune response against the virus begins. This early innate immune response consists of the expression of hundreds of pro-inflammatory and anti-viral genes that stimulates subsequent innate and adaptive immunity. The early innate response in infected cells is mediated by intracellular signaling pathways composed of pattern recognition receptors (PRRs), adapters, kinases, and transcriptions factors. These pathways are tightly regulated by complex networks of post-translational modifications, including ubiquitination. Numerous ubiquitinases and deubiquitinases make these modifications reversible and highly dynamic. The intricate nature of the signaling pathways and their regulation offers the opportunity for fine-tuning the innate immune response against HRSV to control virus replication and immunopathology.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Inmunidad Adaptativa , Anciano , Humanos , Inmunidad Innata , Infecciones por Virus Sincitial Respiratorio/genética , UbiquitinaciónRESUMEN
BACKGROUND AND AIMS: People who inject drugs (PWID) and other marginalized populations with high hepatitis C virus (HCV) infection rates represent a unique challenge for treatment initiation due to health, administrative and social barriers. We analysed the HCV cascade of care (CoC) in some vulnerable subpopulations in Madrid, Spain, when using a mobile point-of-care (PoC). METHODS: From 2019 to 2021, a mobile unit was used to screen active HCV using a linkage-to-care and two-step PoC-based strategy. Viremic participants were grouped into four subgroups: PWID, homeless individuals and people with a mental health disorder (MHD) and alcohol use disorder (AUD). Logistic regression, and Cox and Aalen's additive models were used to analyse associated factors and differences between groups. RESULTS: A prospectively recruited cohort of 214 HCV-infected individuals (73 PWID, 141 homeless, 57 with a MHD and 91 with AUD) participated in the study. The overall HCV CoC analysis found that 178 (83.1%) attended a hospital, 164 (76.6%) initiated direct-acting antiviral therapy and 141 (65.8%) completed therapy, of which 99 (95.2%) achieved sustained virological response (SVR). PWID were significantly less likely to initiate treatment, whereas individuals with AUD waited longer before starting the treatment. Both people with AUD and PWID were significantly less likely to complete HCV treatment. CONCLUSIONS: Overall, SVR was achieved in the majority of the participants treated. However, PWID need better linkage to care and treatment, whereas PWID and AUD need more support for treatment completion.