Mitochondrial Haplogroups and Weight Gain After Initiating ART in Patients with HIV.

We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1,019 treatment-naïve 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 2.90 Kg and 0.98 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.

miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

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.

Diagnostic performance of hepatitis C core antigen assay to identify active infections: A systematic review and meta-analysis.

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%).

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.

Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy.

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.

Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.

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.

IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.

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.

Relative telomere length impact on mortality of COVID-19: Sex differences.

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.

IL7RA rs10491434 polymorphism is related to spontaneous HIV infection control in naïve HIV-infected patients: A retrospective study.

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.

IgG antibody levels against the SARS-CoV-2 spike protein in mother-child dyads after COVID-19 vaccination.

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.

Environmental factors are associated to hospital outcomes in COVID-19 patients during lockdown and post-lockdown in 2020: A nationwide study.

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.

Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk.

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.

Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.

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.

High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity.

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.

Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

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.

Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.

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.

Early innate immune response triggered by the human respiratory syncytial virus and its regulation by ubiquitination/deubiquitination processes.

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.

Differences in the hepatitis C virus cascade of care and time to initiation of therapy among vulnerable subpopulations using a mobile unit as point-of-care.

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.

Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study.

OBJECTIVE: This study evaluated the association of the short-term exposure to environmental factors (relative humidity, temperature, NO2, SO2, O3, PM10, and CO) with hospital admissions due to acute viral lower respiratory infections (ALRI) in children under two years before the COVID-19 era. METHODS: We performed a bidirectional case-crossover study in 30,445 children with ALRI under two years of age in the Spanish Minimum Basic Data Set (MBDS) from 2013 to 2015. Environmental data were obtained from Spain's State Meteorological Agency (AEMET). The association was assessed by conditional logistic regression. RESULTS: Lower temperature one week before the day of the event (hospital admission) (q-value = 0.012) and higher relative humidity one week (q-value = 0.003) and two weeks (q-value<0.001) before the day of the event were related to a higher odds of hospital admissions. Higher NO2 levels two weeks before the event were associated with hospital admissions (q-value<0.001). Moreover, higher concentrations on the day of the event for SO2 (compared to lag time of 1-week (q-value = 0.026) and 2-weeks (q-value<0.001)), O3 (compared to lag time of 3-days (q-value<0.001), 1-week (q-value<0.001), and 2-weeks (q-value<0.001)), and PM10 (compared to lag time of 2-weeks (q-value<0.001)) were related to an increased odds of hospital admissions for viral ALRI. CONCLUSION: Short-term exposure to environmental factors (climatic conditions and ambient air contaminants) was linked to a higher likelihood of hospital admissions due to ALRI. Our findings emphasize the importance of monitoring environmental factors to assess the odds of ALRI hospital admissions and plan public health resources.

Neighborhood environmental factors linked to hospitalizations of older people for viral lower respiratory tract infections in Spain: a case-crossover study.

BACKGROUND: Lower respiratory tract viral infection (LRTI) is a significant cause of morbidity-mortality in older people worldwide. We analyzed the association between short-term exposure to environmental factors (climatic factors and outdoor air pollution) and hospital admissions with a viral LRTI diagnosis in older adults. METHODS: We conducted a bidirectional case-crossover study in 6367 patients over 65 years of age with viral LRTI and residential zip code in the Spanish Minimum Basic Data Set. Spain's State Meteorological Agency was the source of environmental data. Associations were assessed using conditional logistic regression. P-values were corrected for false discovery rate (q-values). RESULTS: Almost all were hospital emergency admissions (98.13%), 18.64% were admitted to the intensive care unit (ICU), and 7.44% died. The most frequent clinical discharge diagnosis was influenza (90.25%). LRTI hospital admissions were more frequent when there were lower values of temperature and O3 and higher values of relative humidity and NO2. The regression analysis adjusted by temperatures and relative humidity showed higher concentrations at the hospital admission for NO2 [compared to the lag time of 1-week (q-value< 0.001) and 2-weeks (q-value< 0.001)] and O3 [compared to the lag time of 3-days (q-value< 0.001), 1-week (q-value< 0.001), and 2-weeks (q-value< 0.001)] were related to a higher odds of hospital admissions due to viral LRTI. Moreover, higher concentrations of PM10 at the lag time of 1-week (q-value = 0.023) and 2-weeks (q-value = 0.002), and CO at the lag time of 3-days (q-value = 0.023), 1-week (q-value< 0.001) and 2-weeks (q-value< 0.001)], compared to the day of hospitalization, were related to a higher chances of hospital admissions with viral LRTI. CONCLUSION: Unfavorable environmental factors (low temperatures, high relative humidity, and high concentrations of NO2, O3, PM10, and CO) increased the odds of hospital admissions with viral LRTI among older people, indicating they are potentially vulnerable to these environmental factors.