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BACKGROUND: Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test-and-treat setting. SETTING: BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV-1 diagnosis before baseline laboratory. METHODS: The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log10 HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test. RESULTS: 36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log10 HIV-RNA was 4.79 (± 0.87) log10 copies/mL and CD4 505 (±253) cells/mm3. The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log10 HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log10 copies/mL, p < 0.001). Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events. CONCLUSION: In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF.
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Fármacos Anti-VIH , Emtricitabina , Infecciones por VIH , Tenofovir , Carga Viral , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Femenino , Adulto , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Carga Viral/efectos de los fármacos , Emtricitabina/uso terapéutico , VIH-1/efectos de los fármacos , VIH-1/genética , Adenina/análogos & derivados , Adenina/uso terapéutico , Piperazinas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Darunavir/uso terapéutico , Alanina/uso terapéutico , Alanina/análogos & derivados , Resultado del Tratamiento , ARN Viral , Sulfonamidas/uso terapéutico , Persona de Mediana Edad , Cobicistat/uso terapéutico , Reino Unido , Combinación de Medicamentos , Amidas , PiridonasRESUMEN
Traditional medical Artificial Intelligence models, approved for clinical use, restrict themselves to single-modal data e.g. images only, limiting their applicability in the complex, multimodal environment of medical diagnosis and treatment. Multimodal Transformer Models in healthcare can effectively process and interpret diverse data forms such as text, images, and structured data. They have demonstrated impressive performance on standard benchmarks like USLME question banks and continue to improve with scale. However, the adoption of these advanced AI models is not without challenges. While multimodal deep learning models like Transformers offer promising advancements in healthcare, their integration requires careful consideration of the accompanying ethical and environmental challenges.
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Flying animals have had to evolve robust and effective guidance strategies for dealing with habitat clutter. Birds and insects use optic flow expansion cues to sense and avoid obstacles, but orchid bees have also been shown to use brightness cues during gap negotiation. Such brightness cues might therefore be of general importance in structuring visually guided flight behaviours. To test the hypothesis that brightness cues also affect gap negotiation behaviours in birds, we presented captive zebra finches Taeniopygia guttata with a symmetric or asymmetric background brightness distribution on the other side of a tunnel. The background brightness conditions influenced both the birds' decision to enter the tunnel aperture, and their flight direction upon exit. Zebra finches were more likely to initiate flight through the tunnel if they could see a bright background through it; they were also more likely to fly to the bright side upon exiting. We found no evidence of the centring response that would be expected if optic flow cues were balanced bilaterally during gap negotiation. Instead, the birds entered the tunnel by targeting a clearance of approximately one wing length from its near edge. Brightness cues therefore affect how zebra finches structure their flight when negotiating gaps in enclosed environments.
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Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood mononuclear cells (PBMCs) using quantitative polymerase chain reaction. In this narrative review, we discuss the usefulness of HTLV-1 PVL quantification and share our experience acquired during more than 30 years of follow-up of people living with HTLV-1 in the UK. Patients with HTLV-1-associated myelopathy have higher PVL than those with asymptomatic infection. This is consistent across studies in different countries. High PVL predates symptom onset for both inflammatory and proliferative diseases. High PVL is essential but not sufficient for the development of HTLV-1-associated diseases. Therefore, PVL quantification can be used to support the care of people living with HTLV-1 by identifying those most at risk of HTLV-1-associated diseases.
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BACKGROUND: Epstein-Barr virus (EBV) is a likely prerequisite for multiple sclerosis (MS) but the underlying mechanisms are unknown. We investigated antibody and T cell responses to EBV in persons with MS (pwMS), healthy EBV-seropositive controls (HC) and post-infectious mononucleosis (POST-IM) individuals up to 6 months after disease resolution. The ability of EBV-specific T cell responses to target antigens from the central nervous system (CNS) was also investigated. METHODS: Untreated persons with relapsing-remitting MS, POST-IM individuals and HC were, as far as possible, matched for gender, age and HLA-DRB1*15:01. EBV load was determined by qPCR, and IgG responses to key EBV antigens were determined by ELISA, immunofluorescence and Western blot, and tetanus toxoid antibody responses by multiplex bead array. EBV-specific T cell responses were determined ex vivo by intracellular cytokine staining (ICS) and cross-reactivity of in vitro-expanded responses probed against 9 novel Modified Vaccinia Ankara (MVA) viruses expressing candidate CNS autoantigens. RESULTS: EBV load in peripheral blood mononuclear cells (PBMC) was unchanged in pwMS compared to HC. Serologically, while tetanus toxoid responses were unchanged between groups, IgG responses to EBNA1 and virus capsid antigen (VCA) were significantly elevated (EBNA1 p = 0.0079, VCA p = 0.0298) but, importantly, IgG responses to EBNA2 and the EBNA3 family antigens were also more frequently detected in pwMS (EBNA2 p = 0.042 and EBNA3 p = 0.005). In ex vivo assays, T cell responses to autologous EBV-transformed B cells and to EBNA1 were largely unchanged numerically, but significantly increased IL-2 production was observed in response to certain stimuli in pwMS. EBV-specific polyclonal T cell lines from both MS and HC showed high levels of autoantigen recognition by ICS, and several neuronal proteins emerged as common targets including MOG, MBP, PLP and MOBP. DISCUSSION: Elevated serum EBV-specific antibody responses in the MS group were found to extend beyond EBNA1, suggesting a larger dysregulation of EBV-specific antibody responses than previously recognised. Differences in T cell responses to EBV were more difficult to discern, however stimulating EBV-expanded polyclonal T cell lines with 9 candidate CNS autoantigens revealed a high level of autoreactivity and indicate a far-reaching ability of the virus-induced T cell compartment to damage the CNS.
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Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Humanos , Herpesvirus Humano 4/inmunología , Femenino , Masculino , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Adulto , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , Reacciones Cruzadas/inmunología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/virología , Linfocitos T/inmunología , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/virología , Antígenos Virales/inmunología , Carga Viral , Mononucleosis Infecciosa/inmunología , Mononucleosis Infecciosa/virología , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Inmunoglobulina G/inmunologíaAsunto(s)
Infecciones por VIH , Infecciones por HTLV-I , Humanos , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Infecciones por HTLV-I/prevención & control , Infecciones por HTLV-I/epidemiología , VIH-1 , Virus Linfotrópico T Tipo 1 Humano , Erradicación de la Enfermedad , Salud GlobalRESUMEN
This study looked at using modified camelina oil to develop sustainable coatings that could replace those derived from petroleum-based materials for use in packaging and other industrial sectors. Solvent-free synthesis of maleic anhydride grafted camelina oil (MCO) was carried out at two different temperatures (200 and 230 °C) to obtain sustainable hydrophobic coating materials for paper substrates. Maleic anhydride grafting of camelina oil was confirmed with attenuated total reflectance-Fourier transform infrared and NMR spectroscopic techniques, and up to 16% grafting of maleic anhydride was achieved, as determined by the titration method. MCO, obtained at different reaction temperatures, was coated onto cellulosic paper and evaluated for its hydrophobicity, mechanical, oxygen, and water vapor barrier properties. Scanning electron microscopy indicated the homogeneous dispersion of coating material onto the paper substrate. MCO-coated papers (MCO-200C paper and MCO-230C paper) provided a water contact angle of above 90° which indicates that the modified oil was working as a hydrophobic coating. Water vapor permeability (WVP) testing of coated papers revealed a reduction in WVP of up to 94% in comparison to the uncoated paper. Moreover, an improved oxygen barrier property was also observed for paper coated with both types of MCO. Analysis of the mechanical properties showed a greater than 70% retention of tensile strength and up to a five-fold increase in elongation at break of coated versus uncoated papers. Overall, the results show that camelina oil, a renewable resource, can be modified to produce environmentally friendly hydrophobic coating materials with improved mechanical and water vapor barrier properties that can serve as a potential coating material in the packaging industry. The results of this research could find applications in the huge paper packaging industries, specially in food packaging.
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BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) is a neglected virus that can cause severe disease and be transmitted from mother to child through breastfeeding. Avoidance of breastfeeding prevents 80% of vertical transmission. The United Kingdom (UK) is currently assessing whether HTLV-1-targeted antenatal screening should be implemented.AimWe aimed to assess the impact and cost-effectiveness of a targeted programme to prevent HTLV-1 vertical transmission in England and Wales.MethodsWe estimated the number of pregnant women who have high risk of HTLV-1 infection based on their or their partner's country of birth. With data from 2021, we used a mathematical model to assess cost-effectiveness of HTLV-1 antenatal screening. We also estimated the annual number of infant infections and the number that could be prevented with screening and intervention.ResultsWe estimate that ca 99,000 pregnant women in England and Wales have high risk of HTLV-1 infection. In the absence of screening, 74 (range:â¯25-211) HTLV-1 infections in infants would be expected to occur every year in England and Wales. Implementation of targeted screening would prevent 58 (range:â¯19-164) infant infections annually. The intervention is effective (incremental 0.00333 quality-adjusted life years (QALY)) and cost-saving (GBP -57.56 (EURâ¯-66.85)).ConclusionOur findings support implementation of HTLV-1 targeted antenatal screening to reduce vertical transmission from mothers to infants in the UK.
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Análisis Costo-Beneficio , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Transmisión Vertical de Enfermedad Infecciosa , Tamizaje Masivo , Diagnóstico Prenatal , Humanos , Infecciones por HTLV-I/prevención & control , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/transmisión , Infecciones por HTLV-I/diagnóstico , Femenino , Embarazo , Gales/epidemiología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Inglaterra/epidemiología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Diagnóstico Prenatal/economía , Tamizaje Masivo/economía , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/epidemiología , Lactante , Recién Nacido , AdultoRESUMEN
Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vß21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vß21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vß21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.
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COVID-19 , Interleucina-18 , Células Asesinas Naturales , Monocitos , Transducción de Señal , Síndrome de Respuesta Inflamatoria Sistémica , Receptor fas , Humanos , Interleucina-18/metabolismo , Niño , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Receptor fas/metabolismo , Receptor fas/genética , Monocitos/inmunología , Monocitos/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/metabolismo , COVID-19/inmunología , COVID-19/virología , COVID-19/metabolismo , COVID-19/complicaciones , Inflamasomas/metabolismo , Inflamasomas/inmunología , SARS-CoV-2/inmunología , Adolescente , Masculino , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Femenino , Preescolar , Análisis de la Célula Individual , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Antígenos CD28/metabolismo , Activación de Linfocitos/inmunología , Receptores de Interleucina-18/metabolismo , Receptores de Interleucina-18/genética , Receptores de Interleucina-18/inmunologíaRESUMEN
DNA-based identification is vital for classifying biological specimens, yet methods to quantify the uncertainty of sequence-based taxonomic assignments are scarce. Challenges arise from noisy reference databases, including mislabelled entries and missing taxa. PROTAX addresses these issues with a probabilistic approach to taxonomic classification, advancing on methods that rely solely on sequence similarity. It provides calibrated probabilistic assignments to a partially populated taxonomic hierarchy, accounting for taxa that lack references and incorrect taxonomic annotation. While effective on smaller scales, global application of PROTAX necessitates substantially larger reference libraries, a goal previously hindered by computational barriers. We introduce PROTAX-GPU, a scalable algorithm capable of leveraging the global Barcode of Life Data System (>14 million specimens) as a reference database. Using graphics processing units (GPU) to accelerate similarity and nearest-neighbour operations and the JAX library for Python integration, we achieve over a 1000 × speedup compared with the central processing unit (CPU)-based implementation without compromising PROTAX's key benefits. PROTAX-GPU marks a significant stride towards real-time DNA barcoding, enabling quicker and more efficient species identification in environmental assessments. This capability opens up new avenues for real-time monitoring and analysis of biodiversity, advancing our ability to understand and respond to ecological dynamics. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.
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Algoritmos , Código de Barras del ADN Taxonómico , Código de Barras del ADN Taxonómico/métodos , Clasificación/métodos , Gráficos por Computador , AnimalesRESUMEN
(1) Background: The evidence base for the management of spontaneous viral controllers in pregnancy is lacking. We describe the management outcomes of pregnancies in a series of UK women with spontaneous HIV viral control (<100 copies/mL 2 occasions before or after pregnancy off ART). (2) Methods: A multi-centre, retrospective case series (1999-2021) comparing pre- and post-2012 when guidelines departed from zidovudine-monotherapy (ZDVm) as a first-line option. Demographic, virologic, obstetric and neonatal information were anonymised, collated and analysed in SPSS. (3) Results: A total of 49 live births were recorded in 29 women, 35 pre-2012 and 14 post. HIV infection was more commonly diagnosed in first reported pregnancy pre-2012 (15/35) compared to post (2/14), p = 0.10. Pre-2012 pregnancies were predominantly managed with ZDVm (28/35) with pre-labour caesarean section (PLCS) (24/35). Post-2012 4/14 received ZDVm and 10/14 triple ART, p = 0.002. Post-2012 mode of delivery was varied (5 vaginal, 6 PLCS and 3 emergency CS). No intrapartum ZDV infusions were given post-2012 compared to 11/35 deliveries pre-2012. During pregnancy, HIV was detected (> 50 copies/mL) in 14/49 pregnancies (29%) (median 92, range 51-6084). Neonatal ZDV post-exposure prophylaxis was recorded for 45/49 infants. No transmissions were reported. (4) Conclusion: UK practice has been influenced by the change in guidelines, but this has had little impact on CS rates.
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Human T cell leukemia virus type 1 (HTLV-1) is the first human oncogenic retrovirus to be discovered and causes two major diseases: a progressive neuro-inflammatory disease, termed HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), and an aggressive malignancy of T lymphocytes known as adult T cell leukemia (ATL). Innate and acquired immune responses play pivotal roles in controlling the status of HTLV-1-infected cells and such, the outcome of HTLV-1 infection. Natural killer cells (NKCs) are the effector cells of the innate immune system and are involved in controlling viral infections and several types of cancers. The ability of NKCs to trigger cytotoxicity to provide surveillance against viruses and cancer depends on the balance between the inhibitory and activating signals. In this review, we will discuss NKC function and the alterations in the frequency of these cells in HTLV-1 infection.
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Introduction: Human T Lymphotropic Virus type 1 (HTLV-1) is a neglected retrovirus associated with many clinical disorders, most notably Adult T-cell Leukemia/Lymphoma and HTLV-1-Associated Myelopathy (HAM). Found in endemic clusters across the world, high prevalence has been reported in minoritized groups who suffer from health inequities. This study investigates the association between HTLV-1 prevalence and the following socioeconomic determinants of health: education, income, and employment, which are markers of health inequity. Methods: A systematic review was conducted by searching the following databases: Ovid/Medline, Embase, Global Health Database, Web of Science, LILACS and SciELO. Primary studies in English, Spanish and Portuguese mentioning HTLV-1 and one of education, income and/or employment were included. A random-effects meta-analysis was performed, and odds ratios (OR) were calculated to determine the association between these socioeconomic determinants of health and HTLV-1 prevalence. Results: 42 studies were included. The likelihood of having HTLV-1 was higher in individuals with less than completed primary education compared to those who completed primary education (OR 1.86 [95% CI 1.34-2.57]; p < 0.01). This may be because individuals with low education have reduced access to and understanding of health information, thus increasing the prevalence of risk factors associated with HTLV-1 infection. No other determinants were found to be statistically significant. Conclusion: Fewer years of schooling are associated with increased likelihood of contracting HTLV-1. Therefore, health promotion materials and public health policies regarding HTLV-1 must consider those with lower educational levels to effectively reduce disease transmission. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335004, identifier (CRD42022335004).
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Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Adulto , Infecciones por HTLV-I/epidemiología , Paraparesia Espástica Tropical/epidemiología , Factores de Riesgo , Factores SocioeconómicosRESUMEN
The mechanism that converts native human transthyretin into amyloid fibrils in vivo is still a debated and controversial issue. Commonly, non-physiological conditions of pH, temperature, or organic solvents are used in in vitro models of fibrillogenesis of globular proteins. Transthyretin amyloid formation can be achieved under physiological conditions through a mechano-enzymatic mechanism involving specific serine proteases such as trypsin or plasmin. Here, we investigate S52P and L111M transthyretin variants, both causing a severe form of systemic amyloidosis mostly targeting the heart at a relatively young age with heterogeneous phenotype among patients. Our studies on thermodynamics show that both proteins are significantly less stable than other amyloidogenic variants. However, despite a similar thermodynamic stability, L111M variant seems to have enhanced susceptibility to cleavage and a lower tendency to form fibrils than S52P in the presence of specific proteases and biomechanical forces. Heparin strongly enhances the fibrillogenic capacity of L111M transthyretin, but has no effect on the S52P variant. Fibrillar seeds similarly affect the fibrillogenesis of both proteins, with a stronger effect on the L111M variant. According to our model of mechano-enzymatic fibrillogenesis, both full-length and truncated monomers, released after the first cleavage, can enter into fibrillogenesis or degradation pathways. Our findings show that the kinetics of the two processes can be affected by several factors, such as intrinsic amyloidogenicity due to the specific mutations, environmental factors including heparin and fibrillar seeds that significantly accelerate the fibrillogenic pathway.
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Amiloidosis , Glicosaminoglicanos , Humanos , Prealbúmina/genética , Amiloidosis/genética , Amiloidosis/metabolismo , Amiloide/metabolismo , HeparinaRESUMEN
The COVID-19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS-CoV-2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long-lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi-subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS-CoV-2 Spike receptor-binding domain, or an antigenic region from SARS-CoV-2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen-specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD-specific IgGs, nucleocapsid-specific IgGs, which neutralised SARS-CoV-2 infection. sEV-based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates.
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COVID-19 , Vesículas Extracelulares , Vacunas , Animales , Humanos , Ratones , SARS-CoV-2 , PandemiasRESUMEN
Human T cell leukemia virus type 1 (HTLV-1) is a retrovirus with preferential CD4+ T cell tropism that causes a range of conditions spanning from asymptomatic infection to adult T cell leukemia and HTLV-1-associated myelopathy (HAM), an inflammatory disease of the CNS. The mechanisms by which HTLV-1 induces HAM are poorly understood. By directly examining the ex vivo phenotype and function of T cells from asymptomatic carriers and patients with HAM, we show that patients with HAM have a higher frequency of CD4+CD8+ double-positive (DP) T cells, which are infected with HTLV-1 at higher rates than CD4+ T cells. Displaying both helper and cytotoxic phenotypes, these DP T cells are highly proinflammatory and contain high frequencies of HTLV-1-specific cells. Mechanistically, we demonstrate that DP T cells arise by direct HTLV-1 infection of CD4+ and CD8+ T cells. High levels of CD49d and CXCR3 expression suggest that DP T cells possess the ability to migrate to the CNS, and when cocultured with astrocytes, DP T cells induce proinflammatory astrocytes that express high levels of CXCL10, IFN-γ, and IL-6. These results demonstrate the potential of DP T cells to directly contribute to CNS pathology.
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Enfermedades de la Médula Ósea , Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Astrocitos , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivosRESUMEN
The relationship between gastrointestinal tract infection, the host immune response, and the clinical outcome of disease is not well understood in COVID-19. We sought to understand the effect of intestinal immune responses to SARS-CoV-2 on patient outcomes including the magnitude of systemic antibody induction. Combining two prospective cohort studies, International Severe Acute Respiratory and emerging Infections Consortium Comprehensive Clinical Characterisations Collaboration (ISARIC4C) and Integrated Network for Surveillance, Trials and Investigations into COVID-19 Transmission (INSTINCT), we acquired samples from 88 COVID-19 cases representing the full spectrum of disease severity and analysed viral RNA and host gut cytokine responses in the context of clinical and virological outcome measures. There was no correlation between the upper respiratory tract and faecal viral loads. Using hierarchical clustering, we identified a group of fecal cytokines including Interleukin-17A, Granulocyte macrophage colony-stimulating factor, Tumor necrosis factorα, Interleukin-23, and S100A8, that were transiently elevated in mild cases and also correlated with the magnitude of systemic anti-Spike-receptor-binding domain antibody induction. Receiver operating characteristic curve analysis showed that expression of these gut cytokines at study enrolment in hospitalised COVID-19 cases was associated negatively with overall clinical severity implicating a protective role in COVID-19. This suggests that a productive intestinal immune response may be beneficial in the response to a respiratory pathogen and a biomarker of a successful barrier response.