Genomic Context of SARS-CoV-2 Outbreaks in Farmed Mink in Spain during Pandemic: Unveiling Host Adaptation Mechanisms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects various mammalian species, with farmed minks experiencing the highest number of outbreaks. In Spain, we analyzed 67 whole genome sequences and eight spike sequences from 18 outbreaks, identifying four distinct lineages: B.1, B.1.177, B.1.1.7, and AY.98.1. The potential risk of transmission to humans raises crucial questions about mutation accumulation and its impact on viral fitness. Sequencing revealed numerous not-lineage-defining mutations, suggesting a cumulative mutation process during the outbreaks. We observed that the outbreaks were predominantly associated with different groups of mutations rather than specific lineages. This clustering pattern by the outbreaks could be attributed to the rapid accumulation of mutations, particularly in the ORF1a polyprotein and in the spike protein. Notably, the mutations G37E in NSP9, a potential host marker, and S486L in NSP13 were detected. Spike protein mutations may enhance SARS-CoV-2 adaptability by influencing trimer stability and binding to mink receptors. These findings provide valuable insights into mink coronavirus genetics, highlighting both host markers and viral transmission dynamics within communities.

Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination / Gravedad comparativa de los casos de COVID-19 causados por las variantes Alfa, Delta u Ómicron de SARS-CoV-2 y su asociación con la vacunación

Background: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. Methods: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June–July 2021; and Delta and Omicron during December 2021–January 2022. Adjusted odds ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. Results: We included 5,345 Alpha and 11,974 Delta infections in June–July and 5,272 Delta and 10,578 Omicron in December–January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46–0.69) or Omicron (0.28; 0.21–0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13–0.21) and Delta (June–July: 0.16; 0.14–0.19; December–January: 0.36; 0.30–0.44) but lower from Omicron (0.63; 0.53–0.75) and individuals aged 65+ years. Conclusion: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.(AU)

Introducción: El objetivo es comprar la gravedad de las infecciones por las variantes Alfa, Delta y Ómicron del SARS-CoV-2 en periodos de co-circulación en España, y estimar la asociación entre vacunación y gravedad en cada variante. Métodos: Las infecciones por SARS-CoV-2 notificadas a la red nacional de vigilancia epidemiológica con información sobre la variante viral y el estado de vacunación se clasificaron como casos si habían requerido hospitalización, o como controles en caso contrario. Alfa y Delta se compararon durante junio-julio de 2021, y Delta y Ómicron durante diciembre de 2021-enero de 2022. Se estimaron odds ratios ajustadas (ORa) mediante regresión logística, comparando la variante y el estado de vacunación entre casos y controles. Resultados: Se incluyeron 5.345 infecciones por variante Alfa y 11.974 por Delta en junio-julio y 5.272 infecciones por Delta y 10.578 por Ómicron en diciembre-enero. Los casos no vacunados por Alfa (aOR: 0,57; IC 95%: 0,46-0,69) u Ómicron (0,28; IC 95%: 0,21-0,36) tuvieron menor probabilidad de hospitalización comparados con Delta. La vacunación completa se asoció a menor hospitalización de forma similar para Alfa (0,16; IC 95%: 0,13-0,21) y Delta (junio-julio: 0,16; IC 95%: 0,14-0,19; diciembre-enero: 0,36; IC 95%: 0,30-0,44) pero menor para Ómicron (0,63; IC 95%: 0,53-0,75) y para individuos con 65+ años. Conclusión: Los resultados indican una mayor gravedad intrínseca de la variante Delta comparada con Alfa u Ómicron, con menor diferencia entre personas vacunadas. La vacunación se asoció a menor hospitalización en todos los grupos.(AU)

Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination.

BACKGROUND: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. METHODS: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted odds ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. RESULTS: We included 5,345 Alpha and 11,974 Delta infections in June-July and 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years. CONCLUSION: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.

Genomic characterisation of respiratory syncytial virus: a novel system for whole genome sequencing and full-length G and F gene sequences.

To advance our understanding of respiratory syncytial virus (RSV) impact through genomic surveillance, we describe two PCR-based sequencing systems, (i) RSVAB-WGS for generic whole-genome sequencing and (ii) RSVAB-GF, which targets major viral antigens, G and F, and is used as a complement for challenging cases with low viral load. These methods monitor RSV genetic diversity to inform molecular epidemiology, vaccine effectiveness and treatment strategies, contributing also to the standardisation of surveillance in a new era of vaccines.

Enhancing SARS-CoV-2 Surveillance through Regular Genomic Sequencing in Spain: The RELECOV Network.

Millions of SARS-CoV-2 whole genome sequences have been generated to date. However, good quality data and adequate surveillance systems are required to contribute to meaningful surveillance in public health. In this context, the network of Spanish laboratories for coronavirus (RELECOV) was created with the main goal of promoting actions to speed up the detection, analyses, and evaluation of SARS-CoV-2 at a national level, partially structured and financed by an ECDC-HERA-Incubator action (ECDC/GRANT/2021/024). A SARS-CoV-2 sequencing quality control assessment (QCA) was developed to evaluate the network's technical capacity. QCA full panel results showed a lower hit rate for lineage assignment compared to that obtained for variants. Genomic data comprising 48,578 viral genomes were studied and evaluated to monitor SARS-CoV-2. The developed network actions showed a 36% increase in sharing viral sequences. In addition, analysis of lineage/sublineage-defining mutations to track the virus showed characteristic mutation profiles for the Delta and Omicron variants. Further, phylogenetic analyses strongly correlated with different variant clusters, obtaining a robust reference tree. The RELECOV network has made it possible to improve and enhance the genomic surveillance of SARS-CoV-2 in Spain. It has provided and evaluated genomic tools for viral genome monitoring and characterization that make it possible to increase knowledge efficiently and quickly, promoting the genomic surveillance of SARS-CoV-2 in Spain.

Hepatitis E Virus Seroprevalence is Associated with Neurodegenerative Disorders in Older People with Dementia: A Case-Control Study.

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.

[Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination]. / Gravedad comparativa de los casos de COVID-19 causados por las variantes Alfa, Delta u Ómicron de SARS-CoV-2 y su asociación con la vacunación.

BACKGROUND: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. METHODS: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted Odds Ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. RESULTS: We included 5,345 Alpha and 11,974 Delta infections in June-July and, 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years. CONCLUSION: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.

Emergence of Progressive Mutations in SARS-CoV-2 From a Hematologic Patient With Prolonged Viral Replication.

We documented a hematologic patient with prolonged SARS-CoV-2 viral replication in whom emergence of viral mutations was documented after the consecutive use of antivirals and convalescent plasma. The virus detected in the last of 12 clinical samples (day 237) had accumulated 22 changes in amino acids and 29 in nucleotides. Some of these changes, such as the E484Q, were mutations of concern as defined by WHO. This finding represents an enormous epidemiological threat and poses a major clinical challenge. Combined antiviral strategies, as well as specific strategies related to the diagnostic approach of prolonged infections for this specific population, may be needed.

HIV screening and retention in care in people who use drugs in Madrid, Spain: a prospective study.

BACKGROUND: The burden of human immunodeficiency virus (HIV) infection in people who use drugs (PWUD) is significant. We aimed to screen HIV infection among PWUD and describe their retention in HIV care. Besides, we also screen for hepatitis C virus (HCV) infection among HIV-seropositive PWUD and describe their linkage to care. METHODS: We conducted a prospective study in 529 PWUD who visited the "Cañada Real Galiana" (Madrid, Spain). The study period was from June 1, 2017, to May 31, 2018. HIV diagnosis was performed with a rapid antibody screening test at the point-of-care (POC) and HCV diagnosis with immunoassay and PCR tests on dried blood spot (DBS) in a central laboratory. Positive PWUD were referred to the hospital. We used the Chi-square or Fisher's exact tests, as appropriate, to compare rates between groups. RESULTS: Thirty-five (6.6%) participants were positive HIV antibodies, but 34 reported previous HIV diagnoses, and 27 (76%) had prior antiretroviral therapy. Among patients with a positive HIV antibody test, we also found a higher prevalence of homeless (P < 0.001) and injection drug use (PWID) (P < 0.001), and more decades of drug use (P = 0.002). All participants received HIV test results at the POC. Of the 35 HIV positives, 28 (80%) were retained in HIV medical care at the end of the HIV screening study (2018), and only 22 (62.9%) at the end of 2020. Moreover, 12/35 (34.3%) were positive for the HCV RNA test. Of the latter, 10/12 (83.3%) were contacted to deliver the HCV results test (delivery time of 19 days), 5/12 (41.7%) had an appointment and were attended at the hospital and started HCV therapy, and only 4/12 (33.3%) cleared HCV. CONCLUSIONS: We found almost no new HIV-infected PWUD, but their cascade of HIV care was low and remains a challenge in this population at risk. The high frequency of active hepatitis C in HIV-infected PWUD reflects the need for HCV screening and reinforcing the link to care.

Detection of active hepatitis C in a single visit and linkage to care among marginalized people using a mobile unit in Madrid, Spain.

BACKGROUND: The burden of hepatitis C virus (HCV) infection among marginalized people in Spain is high, despite the fact that HCV prevalence has decreased in recent years. We aimed to assess the effectiveness of a simplified point-of-care (PoC) model for screening for active HCV infection via a mobile unit and subsequent linkage to care with the assistance of navigators. METHODS: We carried out a prospective study on 2001 participants from Madrid, Spain. A nurse and a navigator/educator screened for hepatitis C in a mobile unit, using the OraQuick HCV Rapid Antibody Test and Xpert HCV VL Fingerstick assay. Participants with active HCV were referred to the hospital the same day with a navigator for evaluation and treatment of HCV. RESULTS: Overall, 1621 (81%) participants had not been exposed to HCV, 380 (18.9%) were positive for HCV antibodies, and 136 (6.8%) had active hepatitis C. Among the latter, 134 (98.5%) received the HCV screening results, 133 (97.8%) had an appointment at the hospital, 126 (92.8%) were seen by a physician once they were at the hospital, and 105 (77.2%) started HCV treatment. Being over 50 years old and a person who uses drugs, particularly people who inject drugs (PWID), was directly associated with active hepatitis C (p<0.05). PWID were the only patients with HCV reinfection (4.3% in people without recent injecting drug use and 5.9% in people with recent injecting drug use). Among PWID, no income and daily alcohol intake were also directly associated with active hepatitis C. People with recent injecting drug use showed the lowest rates of attendance at the hospital (91.8%) and starting HCV treatment (70.4%). CONCLUSION: HCV screening using a two-step PoC-based strategy and its linkage to care was extremely efficient for identifying and treating marginalized people with active hepatitis C, thanks to the use of a mobile unit with personnel and technical equipment, an interdisciplinary team, and collaboration between institutions.

HCV screening based on dried blood samples and linkage to care in people who use drugs: A prospective study.

BACKGROUND: The burden of hepatitis C virus (HCV) infection among people who use drugs (PWUDs) is considerable. We aimed to screen for HCV infection using the fingerstick dried blood spot (DBS) test and to describe the cascade of hepatitis C care among PWUDs in Madrid, Spain. We also evaluated the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) in this population. METHODS: We carried out a prospective study and collected samples and epidemiological data using a mobile unit. Viral infections were tested by immunoassay and RT-PCR assay. PWUDs with a positive result were contacted and referred to a specialized health center to confirm and treat the HCV infection. RESULTS: We studied 529 PWUD samples; 49.7% were from persons who had previously used injection drugs (IDUs). Of these, 152 (28.7%) were positive for HCV antibodies, 122 (23.1%) for HCV RNA, 23 (4.3%) for HBsAg, and two (0.4%) for HDV antibodies (8.7% of those with hepatitis B). People who inject drugs (PWID) more frequently had positive HCV antibody titers (52% vs. 7.3%; p<0.001) and a positive HCV RNA test result (40.2% vs. 7.3%; p<0.001) than non-PWID. The time from sample collection to test results was 19 days. The next 104 individuals (85.2%) with active HCV infection were contacted to report their HCV test results. Of these, 63 (51.6%) had an appointment, 62 (50.8%) were evaluated in the hospital, and 56 (45.9%) started HCV therapy. CONCLUSION: HCV screening using fingerstick DBS was an excellent tool for determining HCV prevalence and other chronic hepatitis viruses (HBV and HDV) in PWUDs. However, linkage to care was limited, mainly with respect to the initiation of HCV therapy.

Gender-based vulnerability in women who inject drugs in a harm reduction setting.

BACKGROUND AND AIMS: In comparison with men, women who use drugs (WWUD) have considerably more frequent and intense experiences with interpersonal violence, sexual abuse and trauma. The aim of this study was to identify issues related to gender-based vulnerability in a group of WWUD attended in a harm reduction facility in Madrid, Spain. MATERIAL AND METHODS: A cross-sectional study was conducted during a screening of blood borne infections. We included WWUD (smoked or injected heroin/cocaine) who were actively screened for HIV, HBV and HCV in a harm reduction setting in Madrid (Spain) from January to December 2017. WWUD were interviewed for gender-based abuse or violence using a face-to-face questionnaire by a trained interviewer. Aspects related to their social-epidemiological condition and gender-based vulnerability were collected. RESULTS: We included 109 women who were actively using drugs. The median age was 39 (IQR 35-47) years, 84.4% were Spanish born, 22.9% were homeless, 43 (41.7%) had ever used injected drugs, 29 (26.6%) were currently using injected drugs, and 27.1% had mental health disorders. Aspects related to gender-based vulnerability were collected. Among those surveyed, they reported having ever suffered emotional or psychological damage (88%), having experienced at least one incident of serious physical injury by a male partner (71%), and having ever suffered sexual abuse (49%). In addition, 28% had ever exchanged sex for money/drugs. When compared to women that did not use injecting drugs, those who injected drugs had more frequently exchanged sex for money/drugs (55% vs 21%, p = 0.003). CONCLUSIONS: A high proportion of WWUD suffer psychological or physical violence by partners denoting gender-based vulnerability. Interventions in harm reduction settings with a multidisciplinary and gender-based approach should be implemented.

Rapid decrease in titer and breadth of neutralizing anti-HCV antibodies in HIV/HCV-coinfected patients who achieved SVR.

The main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with peg-IFNα + ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against five JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVR.

Evaluation of the diagnostic accuracy of laboratory-based screening for hepatitis C in dried blood spot samples: A systematic review and meta-analysis.

The dried blood spot (DBS) is increasingly used for the hepatitis C virus (HCV) screening. Our objective was to perform a meta-analysis of the methodology for HCV screening in DBS samples, particularly in the type of diagnostic assay used. We performed a meta-analysis of all eligible studies published to date (March 2018). The literature search revealed 26 studies: 21 for detection of anti-HCV antibodies and 10 for detection of HCV-RNA. Statistical analyses were performed using Meta-DiSc and STATA (MIDAS module). For detection of HCV antibodies, pooled diagnostic accuracy measures were as follows: sensitivity 96.1%, specificity 99.2%, positive likelihood ratio (PLR) 105, negative likelihood ratio (NLR) 0.04, diagnostic odds ratio (DOR) 2692.9, and summary receiver operating characteristic (SROC) 0.997 ± 0.001. For detection of HCV-RNA, the pooled diagnostic accuracy measures were as follows: sensitivity 97.8%, specificity 99.2%, PLR 44.8, NLR 0.04, DOR 1966.9, and SROC 0.996 ± 0.013. Similar values of pooled diagnostic accuracy measures were found according to the type of anti-HCV antibody detection assay (enzyme-linked immunosorbent assay, rapid diagnostic test, and chemiluminescence assays) and HCV-RNA detection assay (real-time polymerase chain reaction and transcription-mediated amplification). The analysis of external validity showed a high negative predicted value (NPV) for both approaches, but a low positive predicted value (PPV) when prevalence was < 10%, particularly in HCV-RNA tests. Finally, this meta-analysis is subject to limitations, especially publication bias and significant heterogeneity between studies. In conclusion, HCV screening in DBS samples has an outstanding diagnostic performance, with no relevant differences between the techniques used. However, external validity may be limited when the HCV prevalence is low.

Prevalence of hepatitis E infection in HIV/HCV-coinfected patients in Spain (2012-2014).

Hepatitis E virus (HEV) has emerged as a relevant pathogen for HIV-infected patients. However, there is scarce data on HEV infection in HIV/HCV-coinfected individuals with advanced fibrosis, which seems to increase the risk of HEV infection and worsen the prognosis of liver disease. We aimed to determine the prevalence of anti-HEV antibodies, acute hepatitis E, resolved hepatitis E, and exposure to HEV in HIV/HCV-coinfected patients and to evaluate associations with clinical and epidemiological characteristics. We performed a cross-sectional study on 198 HIV/HCV-coinfected patients, 30 healthy controls and 36 HIV-monoinfected patients. We found a low concordance between techniques used for detection of anti-HEV antibodies (ELISA versus Immunoblot), particularly in HIV/HCV-coinfected patients. HIV/HCV-coinfected patients showed the highest prevalence of IgG against HEV, resolved hepatitis E, and exposure to HEV (19.2%, 17.2%, and 22.2% respectively). However, we did not find any samples positive for HEV-RNA nor significant differences between groups. Moreover, HIV/HCV-coinfected patients with CD4 T-cells <350 cells/mm3 had higher prevalence for anti-HEV IgG antibodies, resolved hepatitis E, and exposure to HEV than healthy controls or those with CD4 T-cells ≥ 350 cells/mm3 (p = 0.034, p = 0.035, and p = 0.053; respectively). In conclusion, HIV/HCV-coinfected patients in Spain have a high prevalence for IgG anti-HEV antibodies, resolved hepatitis E, and exposure to HEV; particularly patients with CD4+T-cells <350 cells/mm3.

New Adenovirus Groups in Western Palaearctic Bats.

In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.

The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design.

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience's MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: <7.1 kPa (F0-F1), 7.1-9.4 kPa (F2; significant fibrosis), 9.5-12.4 kPa (F3; advanced fibrosis), and ≥12.5 kPa (F4; cirrhosis). All HCV genotypes were analyzed. The median of follow-up time was 47.9 months. Baseline liver stiffness measurement (LSM) values did not show significant statistical differences for IL7RA genotypes (p>0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932 polymorphism seems to be related to increased risk of liver fibrosis progression in HCV-infected patients. Thus, the rs6897932 polymorphism could be related to the physiopathology of CHC and might be used to successfully stratify the risk of CHC progression.

First cases of European bat lyssavirus type 1 in Iberian serotine bats: Implications for the molecular epidemiology of bat rabies in Europe.

Previous studies have shown that EBLV-1 strains exclusively hosted by Eptesicus isabellinus bats in the Iberian Peninsula cluster in a specific monophyletic group that is related to the EBLV-1b lineage found in the rest of Europe. More recently, enhanced passive surveillance has allowed the detection of the first EBLV-1 strains associated to Eptesicus serotinus south of the Pyrenees. The aim of this study is the reconstruction of the EBLV-1 phylogeny and phylodynamics in the Iberian Peninsula in the context of the European continent. We have sequenced 23 EBLV-1 strains detected on nine E. serotinus and 14 E. isabellinus. Phylogenetic analyses were performed on the first 400-bp-5' fragment of the Nucleoprotein (N) gene together with other 162 sequences from Europe. Besides, fragments of the variable region of the phosphoprotein (P) gene and the glycoprotein-polymerase (G-L) intergenic region were studied on Spanish samples. Phylogenies show that two of the new EBLV-1a strains from Iberian E. serotinus clustered together with French strains from the North of the Pyrenees, suggesting a recent expansion southwards of this subtype. The remaining seven Iberian strains from E. serotinus grouped, instead, within the cluster linked, so far, to E. isabellinus, indicating that spatial distribution prevails over species specificity in explaining rabies distribution and supporting interspecific transmission. The structure found within the Iberian Peninsula for EBLV-1b is in concordance with that described previously for E. isabellinus. Finally, we have found that the current EBLV-1 European strains could have emerged only 175 years ago according to our evolutionary dynamics analyses.

PNPLA3 rs738409 polymorphism is associated with liver fibrosis progression in patients with chronic hepatitis C: A repeated measures study.

BACKGROUND: Host genetic background has been associated with liver fibrosis progression. OBJECTIVE: To analyze the association between the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. STUDY DESIGN: In this retrospective cohort study, 187 patients with chronic HCV infection were included, who had at least two liver stiffness measurements (LSM) by transient elastography during the follow-up. Results were expressed in kilopascals (kPa). The analysis of genetic association was carried out according to additive model by using Generalized Linear Models. RESULTS: No patients had advanced fibrosis/cirrhosis at baseline. During a median follow-up time of 47.9 months, 15 patients developed advanced fibrosis and 17 cirrhosis. In multivariate analysis adjusted by the main clinical and epidemiological covariates, the rs738409 G allele was related to higher increase of LSM values during the follow-up (adjusted arithmetic mean ratio (aAMR) = 1.16 (95%CI = 1.04; 1.29); p = .006) and higher odds of having progression to advanced fibrosis [aOR = 2.03 (95%CI = 1.01; 4.06); p = .045], and progression to cirrhosis [aOR = 3.03 (95%CI = 1.26; 7.30); p = .014]. CONCLUSIONS: PNPLA3 rs738409 polymorphism appears to be related to the increased progression of liver fibrosis in HCV infected patients.

Evaluation of dried blood spot samples for screening of hepatitis C and human immunodeficiency virus in a real-world setting.

Both hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection are underdiagnosed, particularly in low-income countries and in difficult-to-access populations. Our aim was to develop and evaluate a methodology for the detection of HCV and HIV infection based on capillary dry blood spot (DBS) samples taken under real-world conditions. We carried out a cross-sectional study of 139 individuals (31 healthy controls, 68 HCV-monoinfected patients, and 40 HCV/HIV-coinfected patients). ELISA was used for anti-HCV and anti-HIV antibody detection; and SYBR Green RT-PCR was used for HCV-RNA detection. The HIV serological analysis revealed 100% sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The HCV serological analysis revealed a sensitivity of 92.6%, specificity of 100%, PPV of 100%, and NPV of 79.5%. Finally, the HCV-RNA detection test revealed a detection limit of 5 copies/µl with an efficiency of 100% and sensitivity of 99.1%, specificity of 100%, PPV of 100%, and NPV of 96.9%. In conclusion, our methodology was able to detect both HCV infection and HIV infection from the same DBS sample with good diagnostic performance. Screening for HCV and HIV using DBS might be a key strategy in the implementation of national programs for the control of both infections.