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The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.
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Microbioma Gastrointestinal , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Boca/microbiología , Índice de Masa Corporal , Heces/microbiología , Antirretrovirales/uso terapéutico , Saliva/microbiologíaRESUMEN
Much of the debate over the definition and criteria for determining our death has focused on disagreement over the correct biological account of death, i.e., what it means for any organism to die. In this paper, we argue that this exclusive focus on the biology of death is misguided, because it ignores ethical and social factors that bear on the acceptability of criteria for determining our death. We propose that attention shift from strictly biological considerations to ethical and social considerations that bear on the determination of what we call "civil death." We argue for acceptance of a neurological criterion for determining death on grounds that it is the most reasonable way to synthesize biological, ethical, and social considerations about our death..
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The hypothesis of the study was that (1) 3D printed drug delivery systems (DDS) could be characterized in situ during drug release using NMR/MRI techniques in terms of mass transport phenomena description (interfacial phenomena), particularly for systems dealing with two mobile phases (e.g., water and low molecular weight liquid polymer); (2) consequently, it could be possible to deduce how these interfacial mass transport phenomena influence functional properties of 3D printed DDS. Matrix drug delivery systems, prepared using masked stereolithography (MSLA), containing poly(ethylene glycol) diacrylate (PEGDA) and low molecular weight polyethylene glycol (PEG) with ropinirole hydrochloride (RH) were studied as example formulations. The PEGDA to PEG (mobile phase) concentration ratio influenced drug release. It was reflected in spatiotemporal changes in parametric T2 relaxation time (T2) and amplitude (A) images obtained using magnetic resonance imaging (MRI) and T1-T2 relaxation time correlations obtained using low-field time-domain nuclear magnetic resonance (LF TD NMR) relaxometry during incubation in water. For most of the tested formulations, two signal components related to PEG and water were assessed in the hydrated matrices by MRI relaxometry (parametric T2/A images). The PEG component faded out due to outward PEG diffusion and was gradually replaced by the water component. Both components spatially and temporally changed their parameters, reflecting evolving water-polymer interactions. The study shows that dynamic phenomena related to bidirectional mass transport can be quantified in situ using NMR and MRI techniques to gain insight into drug release mechanisms from 3D printed DDS systems.
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Sistemas de Liberación de Medicamentos , Imagen por Resonancia Magnética , Polietilenglicoles , Impresión Tridimensional , Polietilenglicoles/química , Imagen por Resonancia Magnética/métodos , Liberación de Fármacos , Indoles/químicaRESUMEN
PURPOSE OF REVIEW: To unravel the current knowledge and possible link between the gut microbiome and HIV-1 virological control in elite controllers (EC), who can suppress viral replication in the absence of antiretroviral therapy. In addition, to discuss the limitations of current research and propose future research directions. RECENT FINDINGS: EC possess a different gut bacterial microbiota profile in composition and functionality from that of treatment-naive HIV-1 viremic progressors (VP). Specifically, EC have a richer bacterial microbiota as compared to VP, which closely resembles the microbiota in HIV-1 negative healthy controls (HC). Differentially abundant bacteria are found between EC and VP or HC, though results vary among the few existing studies. These data imply that the gut microbiome could contribute to the natural suppression of HIV-1 infection. SUMMARY: An association between the gut microbiome and HIV-1 virological control is evidenced by recent studies. Yet, there are substantial knowledge gaps, and the underlying mechanism of how the microbiome influences the EC phenotype is far from clarified. Future research should consider diverse microbial communities, the complex microbe-host interactions, as well as yet-unidentified causal links between microbiome alterations and HIV-1 disease progression.
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Microbioma Gastrointestinal , Infecciones por VIH , VIH-1 , Humanos , Infecciones por VIH/inmunología , Infecciones por VIH/microbiología , Infecciones por VIH/virología , VIH-1/fisiologíaRESUMEN
According to the mainstream bioethical stance, death constitutes the termination of an organism. This essay argues that such an understanding of death is inappropriate in the usual context of determining death, since it also has a social bearing. There are two reasons to justify this argument. First, the mainstream bioethical definition generates an organismal superposition challenge, according to which a given patient in a single physiological state might be both alive and dead, like Schrödinger's cat. Therefore, there is no clear answer as to whether organ retrieval from a brain-dead patient is an act of killing or not. Second, when combined with the dead donor rule, the mainstream position in the definition of death might lead to ethically unacceptable verdicts, since there is a discrepancy between terminating an organism and depriving someone of moral status.
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Muerte Encefálica , Muerte , Humanos , Muerte Encefálica/diagnóstico , Obtención de Tejidos y Órganos/éticaRESUMEN
Sweden is a country with a low prevalence of human lymphotropic T-cell virus (HTLV) infection, estimated at < 0.005%, but the infection rate is notably higher in specific risk groups such as HTLV-2 among intravenous drug users (IVDU) and people originating from HTLV-1 highly endemic areas. Thus, in the most recent study from 2012, the prevalence of HTLV-2 among IVDU in Stockholm was 3.2%. However, much of the epidemiological data on HTLV in Sweden stems from studies conducted primarily between the 1990s and 2007, and the impact of migration to Sweden during the past 15 years has not been evaluated. Despite Sweden's status as a country with generally low prevalence of HTLV, it is prudent to anticipate and prepare for several potential challenges associated with HTLV infection in the future. Proactive measures to enhance awareness, alongside strategies to curtail transmission and mitigate complications, are crucial for addressing this relatively rare, but significant health issue. In this work, we review the current epidemiological knowledge about HTLV in Sweden and discuss future Swedish perspectives.
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Infecciones por VIH , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Abuso de Sustancias por Vía Intravenosa , Humanos , Suecia/epidemiología , Infecciones por VIH/complicaciones , Abuso de Sustancias por Vía Intravenosa/complicaciones , Linfocitos T , Infecciones por HTLV-I/epidemiologíaRESUMEN
OBJECTIVES: In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described. METHODS: Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020. RESULTS: We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/µL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection. CONCLUSIONS: Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications.
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Antivirales , Infecciones por Citomegalovirus , Infecciones por VIH , Hospitales Universitarios , Humanos , Masculino , Femenino , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/complicaciones , Adulto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Persona de Mediana Edad , Suecia/epidemiología , Recuento de Linfocito CD4 , Antivirales/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Resultado del Tratamiento , Citomegalovirus/aislamiento & purificación , Valganciclovir/uso terapéuticoRESUMEN
In 2017, Michael Nair-Collins formulated his Transitivity Argument which claimed that brain-dead patients are alive according to a concept that defines death in terms of the loss of moral status. This article challenges Nair-Collins' view in three steps. First, I elaborate on the concept of moral status, claiming that to understand this notion appropriately, one must grasp the distinction between direct and indirect duties. Second, I argue that his understanding of moral status implicit in the Transitivity Argument is faulty since it is not based on a distinction between direct and indirect duties. Third, I show how this flaw in Nair-Collins' argument is grounded in the more general problems between preference utilitarianism and desire fulfillment theory. Finally, I present the constructivist theory of moral status and the associated moral concept of death and explain how this concept challenges the Transitivity Argument. According to my view, brain death constitutes a valid criterion of death since brain death is incompatible with the preserved capacity to have affective attitudes and to value anything.
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Muerte Encefálica , Condición Moral , Humanos , Principios Morales , Teoría Ética , Disentimientos y DisputasRESUMEN
T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory T cells can effectively cross-recognize new SARS-CoV-2 variants with a broad array of mutations, such as the emergent hypermutated BA.2.86 variant. Here, we report in two separate cohorts, including healthy controls and individuals with chronic lymphocytic leukemia, that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or vaccination demonstrate resilient immune recognition of BA.2.86. In both cohorts, we found largely preserved SARS-CoV-2 spike-specific CD4+ and CD8+ T cell magnitudes against mutated spike epitopes of BA.2.86. Functional analysis confirmed that both cytokine expression and proliferative capacity of SARS-CoV-2 spike-specific T cells to BA.2.86-mutated spike epitopes are similarly sustained. In summary, our findings indicate that memory CD4+ and CD8+ T cells continue to provide cell-mediated immune recognition to highly mutated emerging variants such as BA.2.86.
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COVID-19 , Células T de Memoria , Humanos , Linfocitos T CD8-positivos , SARS-CoV-2/genética , Epítopos , Glicoproteína de la Espiga del Coronavirus/genética , Anticuerpos AntiviralesRESUMEN
BACKGROUND AND AIMS: Previous studies have shown suboptimal screening for hepatitis D virus (HDV) among patients with chronic hepatitis B (CHB). This study presents the cascade of care for HDV infection in a major secondary referral centre in Southern Stockholm, Sweden. METHODS: HBsAg+ve patients attending Karolinska University Hospital (KUH) from 1992 to 2022 were identified. The prevalence of anti-HDV and/or HDV RNA positivity, interferon (IFN) therapy and maintained virological responses (MVR) after HDV treatment were assessed. Also, time to anti-HDV testing was analysed in relation to liver-related outcomes with logistic regression. RESULTS: Among 4095 HBsAg+ve persons, 3703 (90.4%) underwent an anti-HDV screening; within a median of 1.8 months (range 0.0-57.1) after CHB diagnosis. This screening rate increased over time, to 97.9% in the last decade. Overall, 310 (8.4%) were anti-HDV+ve, of which 202 (65.2%) were HDV RNA+ve. Eighty-five (42%) received IFN, and 9 (10.6%) achieved MVR at the last follow-up. The predictive factors for anti-HDV screening were Asian origin, diagnosis after the year 2012, HIV co-infection (negative factor) and HBV DNA level < 2000 IU/mL in univariable analysis, while HIV co-infection was the only remaining factor in multivariable analysis. Delayed anti-HDV test >5 years was independently associated with worsened liver-related outcomes (adjusted odds ratio = 7.6, 95% CI 1.8-31.6). CONCLUSION: Higher frequency of HDV screening than previously published data could be seen among CHB patients at KUH in a low-endemic setting. Receiving a delayed screening test seems to be associated with worse outcomes, stressing the need of a strategy for timely HDV diagnosis.
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Coinfección , Infecciones por VIH , Hepatitis B , Hepatitis D , Humanos , Antígenos de Superficie de la Hepatitis B , Hepatitis B/complicaciones , Suecia/epidemiología , Coinfección/epidemiología , Hepatitis D/epidemiología , Hepatitis D/complicaciones , Virus de la Hepatitis Delta/genética , Infecciones por VIH/complicaciones , Hepatitis Crónica/complicaciones , ARN , Virus de la Hepatitis B/genéticaRESUMEN
BACKGROUND: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration. METHODS: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 µg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery. RESULTS: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly. CONCLUSION: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).
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COVID-19 , Adulto , Humanos , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Hospitales , Resultado del TratamientoRESUMEN
Although mRNA SARS-CoV-2 vaccines are generally safe and effective, in certain immunocompromised individuals they can elicit poor immunogenic responses. Among these individuals, people living with HIV (PLWH) have poor immunogenicity to several oral and parenteral vaccines. As the gut microbiome is known to affect vaccine immunogenicity, we investigated whether baseline gut microbiota predicts immune responses to the BNT162b2 mRNA SARS-CoV-2 vaccine in healthy controls and PLWH after two doses of BNT162b2. Individuals with high spike IgG titers and high spike-specific CD4+ T-cell responses against SARS-CoV-2 showed low α-diversity in the gut. Here, we investigated and presented initial evidence that the gut microbial composition influences the response to BNT162b2 in PLWH. From our predictive models, Bifidobacterium and Faecalibacterium appeared to be microbial markers of individuals with higher spike IgG titers, while Cloacibacillus was associated with low spike IgG titers. We therefore propose that microbiome modulation could optimize immunogenicity of SARS-CoV-2 mRNA vaccines.
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COVID-19 , Microbioma Gastrointestinal , Infecciones por VIH , Humanos , Vacunas contra la COVID-19 , Vacuna BNT162 , COVID-19/prevención & control , SARS-CoV-2 , Vacunación , ARN Mensajero , Inmunoglobulina GRESUMEN
Patients with end-stage chronic kidney disease show higher systemic oxidative stress and exhale more hydrogen peroxide (H2O2) than healthy controls. Kidney transplantation reduces oxidative stress and H2O2 production by blood polymorphonuclear leukocytes (PMNs). Kidney transplant recipients (KTRs) may be predisposed to an impairment of lung diffusing capacity due to chronic inflammation. Lung function and H2O2 concentration in the exhaled breath condensate (EBC) were compared in 20 KTRs with stable allograft function to 20 healthy matched controls. Serum interleukin eight (IL-8) and C-reactive protein (CRP), blood cell counts, and spirometry parameters did not differ between groups. However, KTRs showed lower total lung diffusing capacity for carbon monoxide, corrected for hemoglobin concentration (TLCOc), in comparison to healthy controls (92.1 ± 11.5% vs. 102.3 ± 11.9% of predicted, p = 0.009), but similar EBC H2O2 concentration (1.63 ± 0.52 vs. 1.77 ± 0.50 µmol/L, p = 0.30). The modality of pre-transplant renal replacement therapy had no effect on TLCOc and EBC H2O2. TLCOc did not correlate with time after transplantation. In this study, TLCOc was less reduced in KTRs in comparison to previous reports. We suggest this fact and the non-elevated H2O2 exhalation exhibited by KTRs, may result perhaps from the evolution of the immunosuppressive therapy.
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Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging SARS-CoV-2 subvariants, it is necessary to assess whether other components of adaptive immunity generate resilient and protective responses against infection. We assessed T cell responses in 279 individuals, covering five different immunodeficiencies and healthy controls, before and after booster mRNA vaccination, as well as after Omicron infection in a subset of patients. We observed robust and persistent Omicron-reactive T cell responses that increased markedly upon booster vaccination and correlated directly with antibody titers across all patient groups. Poor vaccination responsiveness in immunocompromised or elderly individuals was effectively counteracted by the administration of additional vaccine doses. Functionally, Omicron-reactive T cell responses exhibited a pronounced cytotoxic profile and signs of longevity, characterized by CD45RA+ effector memory subpopulations with stem cell-like properties and increased proliferative capacity. Regardless of underlying immunodeficiency, booster-vaccinated and Omicron-infected individuals appeared protected against severe disease and exhibited enhanced and diversified T cell responses against conserved and Omicron-specific epitopes. Our findings indicate that T cells retain the ability to generate highly functional responses against newly emerging variants, even after repeated antigen exposure and a robust immunological imprint from ancestral SARS-CoV-2 mRNA vaccination.
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COVID-19 , Anciano , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Linfocitos T , ARN Mensajero/genética , VacunaciónRESUMEN
BACKGROUND: Immunocompromised patients have varying responses to SARS-CoV-2 mRNA vaccination. However, there is limited information available from prospective clinical trial cohorts with respect to long-term immunogenicity-related responses in these patient groups following three or four vaccine doses, and in applicable cases infection. METHODS: In a real-world setting, we assessed the long-term immunogenicity-related responses in patients with primary and secondary immunodeficiencies from the prospective open-label clinical trial COVAXID. The original clinical trial protocol included two vaccine doses given on days 0 and 21, with antibody titres measured at six different timepoints over six months. The study cohort has subsequently been followed for one year with antibody responses evaluated in relation to the third and fourth vaccine dose, and in applicable cases SARS-CoV-2 infection. In total 356/539 patients were included in the extended cohort. Blood samples were analysed for binding antibody titres and neutralisation against the Spike protein for all SARS-CoV-2 variants prevailing during the study period, including Omicron subvariants. SARS-CoV-2 infections that did not require hospital care were recorded through quarterly in-person, or phone-, interviews and assessment of IgG antibody titres against SARS-CoV-2 Nucleocapsid. The original clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659). FINDINGS: The third vaccine dose significantly increased Spike IgG titres against all the SARS-CoV-2 variants analysed in all immunocompromised patient groups. Similarly, neutralisation also increased against all variants studied, except for Omicron. Omicron-specific neutralisation, however, increased after a fourth dose as well as after three doses and infection in many of the patient subgroups. Noteworthy, however, while many patient groups mounted strong serological responses after three and four vaccine doses, comparably weak responders were found among patient subgroups with specific primary immunodeficiencies and subgroups with immunosuppressive medication. INTERPRETATION: The study identifies particularly affected patient groups in terms of development of long-term immunity among a larger group of immunocompromised patients. In particular, the results highlight poor vaccine-elicited neutralising responses towards Omicron subvariants in specific subgroups. The results provide additional knowledge of relevance for future vaccination strategies. FUNDING: The present studies were supported by grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and Karolinska Institutet.
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COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Estudios de Seguimiento , Huésped Inmunocomprometido , Estudios Prospectivos , ARN Mensajero , VacunaciónRESUMEN
The mainstream concept of death-the biological one-identifies death with the cessation of an organism. In this article, I challenge the mainstream position, showing that there is no single well-established concept of an organism and no universal concept of death in biological terms. Moreover, some of the biological views on death, if applied in the context of bedside decisions, might imply unacceptable consequences. I argue the moral concept of death-one similar to that of Robert Veatch-overcomes such difficulties. The moral view identifies death with the irreversible cessation of a patient's moral status, that is, a state when she can no longer be harmed or wronged. The death of a patient takes place when she is no longer capable of regaining her consciousness. In this regard, the proposal elaborated herein resembles that of Veatch yet differs from Veatch's original project since it is universal. In essence, it is applicable in the case of other living beings such as animals and plants, provided that they have some moral status.
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Condición Moral , Principios Morales , Animales , Femenino , HumanosRESUMEN
The paper is dedicated to modeling electricity spot prices and pricing forward contracts on energy markets. The underlying dynamics of electricity spot prices is governed by a stochastic mean reverting diffusion with jumps having mixed-exponential distribution. Application of financial mathematics and stochastic methods enabled the derivation of the analytical formula for the forward contract's price in a crisp case. Since the model parameters' incertitude is considered, their fuzzy counterparts are introduced. Utilization of fuzzy arithmetic enabled deriving an analytical expression for the futures price and proposing a modified method for decision-making under uncertainty. Finally, numerical examples are analyzed to illustrate our pricing approach and the proposed financial decision-making method.
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OBJECTIVE: Why people with HIV-1 on ART (PWH ART ) display convoluted metabolism and immune cell functions during prolonged suppressive therapy is not well evaluated. In this study, we aimed to address this question using multiomics methodologies to investigate immunological and metabolic differences between PWH ART and HIV-1 negative individuals (HC). DESIGN: Cross-sectional study. METHODS: Untargeted and targeted metabolomics was performed using gas and liquid chromatography/mass spectrometry, and targeted proteomics using Olink inflammation panel on plasma samples. The cellular metabolic state was further investigated using flow cytometry and intracellular metabolic measurement in single-cell populations isolated by EasySep cell isolation. Finally, flow cytometry was performed for deep-immunophenotyping of mononuclear phagocytes. RESULTS: We detected increased levels of glutamate, lactate, and pyruvate by plasma metabolomics and increased inflammatory markers (e.g. CCL20 and CCL7) in PWH ART compared to HC. The metabolite transporter detection by flow cytometry in T cells and monocytes indicated an increased expression of glucose transporter 1 (Glut1) and monocarboxylate transporter 1 (MCT-1) in PWH ART . Single cell-type metabolite measurement identified decreased glucose, glutamate, and lactate in monocytic cell populations in PWH ART . Deep-immunophenotyping of myeloid cell lineages subpopulations showed no difference in cell frequency, but expression levels of CCR5 were increased on classical monocytes and some dendritic cells. CONCLUSIONS: Our data thus suggest that the myeloid cell populations potentially contribute significantly to the modulated metabolic environment during suppressive HIV-1 infection.
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Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , Estudios Transversales , Células Mieloides , Glutamatos , LactatosRESUMEN
PROPOSE: Pregnancy is a risk factor for severe COVID-19. Treatment with monoclonal antibodies has been shown to decrease the risk of progression to severe COVID-19, but there are few reports on treating pregnant women. Here, we describe the clinical outcome of seven hospitalized pregnant women treated with the casirivimab-imdevimab. METHODS/RESULTS: Seven unvaccinated pregnant patients hospitalized due to COVID-19 met the monoclonal antibodies treatment criteria applied at our center. After consultations with obstetricians, the decisions to administer casirivimab-imdevimab to halt the progression of COVID-19 were made by two senior infectious diseases specialists. No patient experienced an adverse drug reaction, and only one patient progressed to severe disease. Two patients had a cesarian section performed during hospitalization, both with delivery of healthy babies. Three patients gave birth to healthy babies at a later time point, while two pregnancies are ongoing. CONCLUSION: The hospitalized pregnant patients who received monoclonal antibodies due to COVID-19 had favorable outcomes, but further research is recommended to fully assess safety and efficacy of monoclonal antibody treatment in pregnancy.