BACKGROUND:Only a subset of individuals infected with SARS‑CoV‑2 develop severe COVID‑19. Improved tools for early diagnosis and prognostication are needed. We hypothesized that unsupervised analysis of detailed circulating proteomes could reveal biologically meaningful patient endotypes and help identify individuals at elevated risk of severe outcomes. METHODS:We performed unsupervised stratification of the circulating proteome in 731 SARS‑CoV‑2 PCR‑positive participants from the Biobanque québécoise de la COVID‑19 (BQC19), representing a range of disease severities. We also developed a prognostic model based solely on clinical laboratory measurements and applied it to 903 patients recruited across early pandemic waves (2020-2022) to generalize identified endotypes. RESULTS:Six proteomic endotypes (EPs) emerged. Endotype EP6 showed the highest frequencies of ICU admission, ARDS, and mortality. EP6 was marked by elevated C‑reactive protein, D‑dimer, interleukin‑6, ferritin, soluble fms‑like tyrosine kinase‑1, increased neutrophils, and reduced lymphocyte counts. SHC4 emerged as a protein quantitative trait locus associated with EP6. Among EP6 patients requiring mechanical ventilation, we observed alterations in lipoprotein metabolism, and alpha‑L‑iduronidase levels inversely correlated with duration of ventilation. CONCLUSIONS:Unsupervised proteomic analysis identified biologically coherent endotypes that advance understanding of acute lung injury in COVID‑19 and support improved diagnostic and prognostic strategies.

The COVID-19 pandemic underscored the urgent need for strong biobanking infrastructures to facilitate rapid research and innovation in public health emergencies. The COVID-19 Québec Biobank (BQC19), launched in March 2020, serves as a pioneering initiative to address this demand, enabling the collection, storage, and sharing of biological samples and data to advance diagnostics, therapeutics, and epidemiological research. This article examines the development and operational framework of BQC19, highlighting five key themes central to its success. First, BQC19's anticipatory governance model emphasizes adaptability, leveraging strategic foresight to maintain ethical and efficient operations during the pandemic. Second, the initiative's harmonized yet flexible consent processes ensured participant autonomy and compliance with evolving clinical and public health contexts. Third, BQC19's collaborative governance framework facilitated seamless interinstitutional cooperation, supported by standardized operating procedures and localized manuals of procedures. Fourth, streamlined data access mechanisms, managed by an independent data access committee, promoted ethical and equitable data sharing, balancing privacy considerations with research accessibility. Last, BQC19 demonstrates the transferability of its infrastructure to other health challenges, providing a scalable, ethical, and collaborative model for future public health crises. Through centralized data management, preestablished legal agreements, and tiered access protocols, BQC19 has significantly reduced response times and operational inefficiencies. Its achievements showcase the potential of biobanks in fostering global health collaboration, enabling rapid research mobilization, and addressing emerging health threats. BQC19's legacy lies in its ability to integrate innovation, ethics, and collaboration into a sustainable framework for public health preparedness.

BackgroundThe crosstalk between intestinal epithelial cells (IEC) and CD4+ T-cells is essential for the maintenance of mucosal homeostasis, but its role in governing HIV-1 latency versus reactivation in gut-homing/resident T-cells remains poorly documented. We previously demonstrated that the Th17-lineage cytokine IL-17A transcriptionally reprograms IEC for promoting viral outgrowth in CD4+ T-cells of antiretroviral therapy (ART)-treated people with HIV-1 (PWH). These effects coincided with the downregulation of IL-32, a cytokine with documented antiviral properties and identified as a marker for HIV-1 disease progression and cardiovascular disease risk. Here, we aimed to identify modulators of IL-32 expression and to define the impact of IEC expressing IL-32 on HIV-1 outgrowth in neighboring CD4+ T-cells carrying viral reservoirs.MethodsHT-29 IEC were activated with TNF and/or IL-22, IL-26, all-trans retinoic acid (ATRA) and rosiglitazone (RGZ). CRISPR/Cas9 gene editing was used to knockout (KO) IL32 in IEC, with efficiency/off-target effect assessments performed using TIDE and whole-genome RNA-Sequencing. IL-32β/γ/ϵ mRNA/protein were quantified by RT-PCR/ELISA. An IEC-based viral outgrowth assay (VOA) was performed with CD4+ T-cells of ART-treated PWH. Soluble/intracellular HIV-p24 levels were measured by ELISA/flow cytometry.ResultsIn combination with TNF, IL-22 upregulated IL-32β/ϵ, RGZ increased IL-32β, ATRA decreased IL-32β/γ/ϵ, while IL-26 had no impact in IEC. HIV-1 outgrowth in IEC:T-cell co-cultures was not affected by IL-22/RGZ/ATRA-mediated changes in IL-32 expression. The analysis of differentially expressed genes in control versus IL32KO IEC revealed minor differences in transcriptional profiles before/after exposure to TNF, while the IL-32 mRNA/protein expression was induced by TNF in control but not IL32KO IEC. Finally, TNF-activated control versus IL32KO IEC supported with similar efficacy HIV-1 outgrowth in CD4+ T-cells of PWH.ConclusionsWe identified IL-22, ATRA and RGZ as novel regulators of IL-32 expression in TNF-primed IEC and demonstrated that pharmacological and genetic modulation of IL-32 expression in IEC has no major impact on HIV-1 outgrowth from co-cultured CD4+ T-cells of ART-treated PWH carrying viral reservoirs. By excluding its role in modulating HIV reservoir latency/reactivation at intestinal barrier level, these results support the idea of testing the potential use of IL-32 as a novel therapeutic target to reduce comorbidities in ART-treated PWH.

Genome-wide association studies performed in COVID-19 patients have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and disease severity. However, the underlying cis-regulatory genetic factors contributing to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we use single-cell RNA-sequencing to quantify genetic contributions to cis-regulatory variation in 361,119 peripheral blood mononuclear cells of 63 acute COVID-19 patients, 39 convalescent samples, and 106 healthy controls. Expression quantitative trait loci mapping across cell types within each disease state group reveals thousands of cis-associated variants, of which hundreds are detected exclusively in immune cells derived from acute patients. Patient-specific genetic effects dissipate as infection resolves, suggesting that distinct gene regulatory networks are at play in the active infection state. Further, 20.3% of tested loci demonstrate significant cell state interactions with genotype, with pathways related to interferon responses and oxidative phosphorylation showing pronounced cell state-dependent variation, predominantly in CD14+ monocytes. Overall, we estimate that 16.8% of tested genes exhibit gene-environment interaction effects, highlighting the importance of environmental modifiers in the transcriptional regulation of the immune response to SARS-CoV-2. Our findings argue for the existence of extensive gene-environment effects among patients responding to an infection.

BACKGROUND:Heavily treatment-experienced (HTE) people with HIV (PWH) have limited antiretroviral therapy (ART) treatment options, putting them at greater risk of unfavorable human immunodeficiency virus 1 (HIV-1) disease progression. Fostemsavir (BMS-663068) efficiently suppressed viremia and increased CD4 count when combined with other antiretrovirals in HTE PWH. Its active metabolite, temsavir (BMS-626529, GSK2616713), binds a conserved pocket within the envelope glycoprotein (Env) CD4 binding site and prevents CD4-induced conformational changes. Temsavir effect on Env conformation profoundly alters its glycosylation and cleavage, thereby modifying its antigenicity and reducing gp120 shedding. Here we evaluated if fostemsavir treatment in PWH modulated the levels of nonneutralizing gp120 CD4-induced (CD4i) antibodies (Abs) associated with CD4 depletion in vitro and in PWH. METHODS:We measured the levels of anti-gp120 CD4i Abs in plasma samples taken before and after fostemsavir treatment in HTE participants from the BRIGHTE trial and the PRESTIGIO registry and compared them to those of a control ART-treated group from the SAILING trial. RESULTS:We observed a significant decline of anti-gp120 CD4i Abs in the 2 fostemsavir-treated HTE groups, but not in the control group. Moreover, this effect was unique to anti-gp120 CD4i Abs, as no significant changes were observed in the levels of antibodies targeting Gag. Functionally, this decline in CD4i Abs was associated with a reduced capacity of plasma to recognize and eliminate uninfected primary CD4+ T cells coated with soluble gp120. CONCLUSIONS:Altogether, fostemsavir may provide additional immune benefits to PWH, beyond blocking viral entry, by reducing anti-gp120 CD4i Abs levels. CLINICAL TRIALS REGISTRATION:NCT04098315, NCT01231516, and NCT02362503.

Despite antiretroviral therapy (ART), people with HIV (PWH) face immunological ageing and accelerated comorbidities including coronary artery disease (CAD). Gut mucosal damage, chronic inflammation, and Tryptophan (Trp) catabolism into Kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO), are associated with HIV disease progression and atherosclerosis. Thus, we comprehensively assessed the interplay between these perturbations in PWH with subclinical CAD under ART. Plasma levels of inflammatory mediators, Trp metabolites, and immune cell subset phenotyping were assessed on blood specimens from PWH and HIV seronegative participants with or without CAD diagnosed by cardiac computed tomography angiography from the Canadian HIV Aging Cohort Study. Levels of gut damage markers regenerating islet-derived protein 3 alpha (REG3α), intestinal fatty-acid binding protein (I-FABP) and soluble CD14 (sCD14) were increased in PWH, but only I-FABP was associated with CAD. Among inflammatory soluble markers, soluble receptor type II for the tumor necrosis factor (sTNFRII) was elevated in PWH, while increased interferon-gamma (IFN-γ) and interleukin (IL)-17A levels were associated with CAD. Regardless of CAD, PWH were characterized by upregulated IDO/Kyn pathway and increased Trp metabolites Kyn, 3-hydroxykynurenine (3-H-Kyn), anthranilic acid, along with decreased xanthurenic acid (Xan acid). Accordingly, HIV+CAD+ participants exhibited highest Kyn/Trp and 3-H-Kyn/Xan acid ratios. CAD+ participants had increased classical CD14+ and decreased non-classical CD16+ monocyte frequencies, regardless of HIV status. HIV status was associated with increased frequencies of Ki67+ proliferating, CD28−CD57+ senescent and CCR4+CXCR3+ CD4 and CD8 T-cells, while T-cell and regulatory T-cells (Treg) atheroprotective CD73-expressing subsets were decreased in PWH. In PWH, subclinical CAD is associated with a distinctive gut-heart immuno-metabolic feature and inflammaging characterized by elevated plasma markers of gut mucosal damage, increased IFN-γ levels and IDO pathway activity, and altered monocyte and T-cell subsets. Gut–Heart immuno-metabolic disruption and subclinical Coronary Artery Disease (CAD) in chronic HIV infection. Image was made in part using Servier Medical Art (https://smart.servier.com/).

ABSTRACT The HIV-1 envelope glycoprotein (Env) represents the only viral antigen at the surface of infected cells, making it an ideal target for antibody-based therapies. Most antibodies elicited in people with HIV (PWH) do not recognize Env in its native “closed” conformation but readily bind to Env when it samples the CD4-bound “open” conformation. Downregulation of CD4 at the surface of infected cells by the viral accessory proteins Nef and Vpu prevents the premature opening of Env and has been shown to protect infected cells from antibody-dependent cellular cytotoxicity (ADCC) mediated by PWH plasma. Here, we report that deletion of Nef and Vpu from primary infectious molecular clones renders infected cells vulnerable to antibody-dependent cellular phagocytosis (ADCP) mediated by PWH plasma. This is in part linked to the premature engagement of Env with CD4. In agreement with an “open” Env being vulnerable to ADCP, small CD4-mimetic compounds (CD4mc) sensitize in vitro -infected cells and ex vivo -expanded CD4 T cells to ADCP mediated by autologous monocytes in the presence of PWH plasma. This effect was further improved by increasing cell surface Env through IFN-induced BST-2 upregulation. IMPORTANCE Developing new therapies to eliminate HIV-1-infected cells is essential to decrease the size of the HIV-1 reservoir. Fc-effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), have shown potential in eliminating in vitro- infected cells and ex vivo- expanded infected cells from people with HIV, decreasing the size of the reservoir, and delaying viral rebound in humanized mice. Here, we report that antibody-dependent cellular phagocytosis (ADCP) can also be harnessed to eliminate HIV-1-infected cells. We show that infected cells harboring “open” Env conformations are susceptible to ADCP-mediated killing in the presence of plasma from people with HIV. A better understanding of the contribution of different Fc-effector functions in the elimination of infected cells could help guide the development of new therapeutic approaches toward an HIV-1 cure.

Noncommunicable diseases (NCDs), particularly cardiovascular diseases (CVDs), hypertension and diabetes, are major contributors to morbidity and mortality globally and in Rwanda, where the dual burden of HIV and NCDs is increasing. Evidence remains limited on how biological, behavioural, social, environmental and health-system determinants influence cardiovascular and metabolic outcomes among people living with HIV (PLHIV) in Rwanda. The NCOHIRWA cohort was established to prospectively investigate determinants associated with CVDs, hypertension, diabetes and related NCD outcomes among PLHIV, newly diagnosed PLHIV and people without HIV (PWoH). This manuscript presents the protocol for the NCOHIRWA cohort study. The NCOHIRWA study is a prospective cohort with a mixed-methods implemented across 12 health facilities providing HIV and NCD services in Rwanda. Adults aged ≥ 18 years, including PLHIV, newly diagnosed PLHIV and PWoH were enrolled beginning in March 2021 and will be followed longitudinally for 10 years. Baseline and follow-up data capture sociodemographic characteristics, behavioural, psychosocial, family history of NCDs, environmental and health-system factors, and clinical, anthropometric and laboratory measures relevant to cardiovascular and metabolic health. A total of 1,546 participants with complete baseline data were included, comprising 1,234 (79.8

Background. People with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART) have increased risks of non-AIDS comorbidities. Growth differentiation factor 15 (GDF-15) is a mitokine released upon mitochondrial stress and is a validated aging biomarker. Herein, we assessed associations between plasma GDF-15 levels, inflammation, and HIV reservoir markers in ART-treated people with HIV (PWH). Methods. Blood samples were collected from 78 ART-naive, 140 ART-treated PWH (median ART duration, 15.6 years) and 83 uninfected control participants. GDF-15 and markers of inflammation were quantified in plasma by enzyme-linked immunosorbent assay (ELISA) and multiplex assays. Integrated HIV DNA levels were measured in isolated CD4 T cells by ultrasensitive quantitative Alu polymerase chain reaction. Intracellular GDF-15 production was assessed ex vivo by flow cytometry, and in supernatants by ELISA after in vitro stimulations. Results. Plasma GDF-15 levels were higher in ART-treated PWH compared to ART-naive PWH or controls, independently of age. Ex vivo, GDF-15 was produced by classical, intermediate, and nonclassical monocytes, but absent in T cells, B cells, natural killer cells, and dendritic cells. Plasma and monocyte intracellular GDF-15 levels correlated strongly (r = 0.96, P = .002). Plasma GDF-15 levels did not correlate with the majority of inflammatory markers quantified in plasma. Conversely, plasma GDF-15 levels correlated with the validated non-AIDS inflammatory comorbidity marker suPAR (soluble urokinase plasminogen activator receptor; r = 0.59, P < .001), as well as with integrated HIV DNA levels in CD4+ T cells (r = 0.47, P < .01). Conclusions. Plasma levels of GDF-15, mainly produced by monocytes, were positively associated with HIV reservoir markers and coincided with increased level of suPAR, suggesting that HIV persistence is associated with increased mitochondrial stress and comorbidity risks in ART-treated PWH.

BACKGROUND:Despite effective antiretroviral therapy (ART), neurocognitive impairment (NCI) persists in 30-50% of virally suppressed people with HIV (VS PWH). The mechanisms underlying this persisting NCI remain incompletely understood. Soluble gp120 (sgp120) has been detected in the plasma of PWH on ART and may contribute to inflammation and CD4 + T-cell depletion in the presence of non-neutralizing anti-cluster A antibodies (Abs). gp120 can induce neurotoxicity, leading to neuronal damage both in vitro and in transgenic mice. OBJECTIVE:To determine whether sgp120 and anti-cluster A Abs are detectable in the cerebrospinal fluid (CSF) of VS PWH and to evaluate whether their presence is associated with domain-specific neurocognitive performance. METHODS:We analyzed paired plasma and CSF samples from 146 VS PWH and 37 unsuppressed PWH. Neurocognitive performance was assessed using a comprehensive neuropsychological testing battery across multiple domains, from which demographically adjusted T -scores for each test were derived. Levels of sgp120 and anti-cluster A Abs were measured to evaluate their association with neurocognitive performance in PWH. RESULTS:Sgp120 and anti-cluster A Abs were detected in the CSF of 11 and 26% of VS PWH, respectively. Detection of CSF sgp120 was associated with lower neurocognitive motor-domain T -scores (Mann-Whitney U , P  = 0.039; Cliff's δ  = -0.33). This association was confined to sgp120 in the CSF and was not observed for sgp120 in plasma or for anti-HIV antibodies in the CSF. CONCLUSION:These findings suggest that central nervous system (CNS) exposure to sgp120 may contribute to poorer motor neurocognitive performance in VS PWH. Strategies targeting CSF sgp120-related biomarkers warrant further investigation as potential approaches to mitigate NCI in VS PWH.

ABSTRACT People living with HIV-1 (PWH) receiving antiretroviral therapy (ART) exhibit an increased cardiovascular disease (CVD) risk. Coronary atherosclerotic plaque formation is linked to chronic immune activation, a process fueled in PWH by additional mechanisms likely including residual HIV-1 production and microbial translocation from the gut during ART. Our previous studies demonstrated that aldehyde dehydrogenase (ALDH), an enzyme converting vitamin A into retinoic acid (RA), is upregulated in myeloid cells upon exposure to viral/bacterial/fungal products and that RA promotes HIV-1 production. To explore the link between ALDH/RA pathway and CVD risk, we used PBMC/plasma from ART-treated PWH (PWH + ART; n=51) and people without HIV-1 (Pw/oH; n=63) from the Canadian HIV/Aging Cohort Study, with/without subclinical coronary atherosclerosis, measured by coronary computed tomography angiography. ALDH expression was analyzed by flow cytometry on monocyte subsets, dendritic cells, and CD4 + T-cells. Unsupervised t-SNE-guided FlowSOM analysis associated top ALDH activity with a monocyte phenotype. The frequency of ALDH + monocytes and plasma levels of RA and retinol binding protein 4 were increased in PWH + ART versus Pw/oH, with the highest RA levels coinciding with detectable plasma levels of soluble HIV-1 gp120. Multivariate regression models linked ALDH activity in monocytes to subclinical coronary atherosclerosis ( i.e., total plaque volume, low attenuated plaque volume, coronary artery calcification score) presence/burden in PWH + ART, independently of Framingham risk score. Finally, ALDH + monocyte frequency and RA levels positively correlated with pericoronary fat attenuation index, an emerging CVD predictor. Thus, ALDH/RA pathway may represent a new marker of metabolic/immune dysfunction contributing to CVD risk in ART-treated PWH. KEY POINTS ALDH activity in blood monocytes is increased in people with HIV receiving antiretroviral therapy (ART) compared to people without HIV The frequency of ALDH+ monocytes is positively correlated with the atherosclerotic plaque burden during ART-treated HIV infection Graphical abstract

ABSTRACT Persistence of HIV antigens may drive chronic inflammation, leading to early-onset comorbidity among people living with HIV. We found that the presence of soluble glycoprotein 120 in plasma is associated with increased coronary inflammation, as measured by the pericoronary fat attenuation index (PFAI), a predictor of overt cardiovascular disease.

People with HIV (PWH) have an increased risk of developing cardiovascular disease (CVD). Our recent data demonstrated that the multi-isoform proinflammatory cytokine IL-32 is upregulated in PWH and is associated with arterial stiffness and subclinical atherosclerosis. However, the mechanisms by which IL-32 contributes to the pathogenesis of these diseases remain unclear. Here, we show that while the less expressed IL-32α isoform induces the differentiation of human classical monocytes into the calcium-resorbing osteoclast cells, the dominantly expressed isoforms IL-32β and IL-32γ suppress this function through the inhibition of TGF-β and induce the differentiation of monocytes into the calcium-depositing osteocalcin+ osteoblasts. These results aligned with the increase in plasma levels of osteoprotegerin, a biomarker of vascular calcification, and its association with the presence of coronary artery subclinical atherosclerosis and calcium score in PWH. These findings support a novel role for the proinflammatory cytokine IL-32 in the pathophysiology of CVD by increasing vascular calcification in PWH.

Coronavirus disease 2019 (COVID-19) is a multi-systemic illness that became a pandemic in March 2020. Although environmental factors and comorbidities can influence disease progression, there is a lack of prognostic markers to predict the severity of COVID-19 illness. Identifying these markers is crucial for improving patient outcomes and appropriately allocating scarce resources. Here, an RNA-sequencing study was conducted on blood samples from unvaccinated, hospitalized patients divided by disease severity; 367 moderate, 173 severe, and 199 critical. Using a bioinformatics approach, we identified differentially expressed genes (DEGs), alternative splicing (AS) and alternative polyadenylation (APA) events that were severity-dependent. In the severe group, we observed a higher expression of kappa immunoglobulins compared to the moderate group. In the critical cohort, a majority of AS events were mutually exclusive exons and APA genes mostly had longer 3’UTRs. Interestingly, multiple genes associated with cytoskeleton, TUBA4A, NRGN, BSG, and CD300A, were differentially expressed, alternatively spliced and polyadenylated in the critical group. Furthermore, several inflammation-related pathways were observed predominantly in critical vs. moderate. We demonstrate that integrating multiple downstream analyses of transcriptomics, from moderate, severe, and critical patients confers a significant advantage in identifying relevant dysregulated genes and pathways.

Noncommunicable diseases, primarily cardiovascular diseases (CVDs), are an emerging cause of morbidity in sub-Saharan Africa. Dyslipidaemia, a key modifiable CVD risk factor, is increasing but remains underdiagnosed and undertreated, particularly among people living with HIV (PLHIV), where HIV-related chronic inflammation, antiretroviral therapy (ART), and sociodemographic factors may contribute. This study assessed the prevalence, correlates of dyslipidaemia, and estimated 10-year CVD risk among PLHIV and people without HIV (PWoH) adults in Rwanda. We analysed baseline data from 1,546 adults (1,234 PLHIV and 312 PWoH) enrolled in the NCOHIRWA Cohort from 12 Rwandan health facilities. Data were collected via standardised World Health Organisation (STEP) questionnaires. Dyslipidaemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, and 10-year CVD risk was calculated via the Framingham risk score. For group comparisons, chi-square tests were used. Multivariate logistic regression identified independent predictors of dyslipidaemia, with adjusted odds ratios and 95

Antiretroviral therapy (ART) controls HIV-1 replication in people with HIV-1 (PWH), but immunological restauration is not achieved at mucosal barriers. Intestinal integrity impairment fuels microbial translocation and chronic immune activation, thus heightening the cardiovascular disease (CVD) risk. Here, we sought to identify novel immunological predictors of the HIV and CVD status in the peripheral blood of ART-treated PWH (HIV + ; n=42) and uninfected participants (HIV-; n=40) of the Canadian HIV and Aging Cohort Study (CHACS), with/without subclinical coronary atherosclerotic plaques, measured by Coronary Computed Tomography Angiography as total plaque volume (TPV, mm 3 ). PBMCs were analyzed by flow cytometry for the expression of T-cell lineage (CD45, CD3, CD4, CD8αα, CD8αβ, TCRαβ, TCRγδ), epithelial cell (EpCAM/CD326), activation (HLA-DR), and gut-homing/residency markers (CD69, CD196/CCR6, CD199/CCR9, CD49d/Itgα4, CD103/ItgαE, Itgβ7). CellEngine supervised clustering of the flow cytometry data revealed profound alterations in the CD3 + T-cell pool in relationship with the HIV status, with the accumulation of peculiar CD8 + TCRαβ + and TCRγδ + cells, to the detriment of CD4 + TCRαβ + subsets. FlowJo manual gating further identified CD4 + T-cell subsets with peculiar CD326 + CD69 + CCR6 + ItgαE + and CCR6 + Itgβ7 - phenotypes that were increased in frequency in HIV + versus HIV - participants, together with a decreased frequency of CD8 + T-cells with an intraepithelial lymphocyte (IEL)-like CD3 + CD4 - TCRαβ + TCRγδ - CD8αα + CD8αβ - phenotype. Finally, multivariate logistic regression revealed the predictive capacity of specific T-cell subsets regarding the HIV/CVD status, and TPV values. Of particular relevance, we identified ItgαE + CD8 + , ItgαE - CD8 + , CCR6 + CD4 + , and CCR6 + Itgβ7 - CD4 + T-cell subsets as strong positive predictors of atherosclerotic plaque volume in crude models or upon adjustment for HIV/CVD confounding factors.

While antiretroviral therapy efficiently suppresses viral replication, inflammation and immune dysfunction persist in some people living with HIV-1 (PLWH). Soluble gp120 (sgp120) has been detected in PLWH plasma and its presence is linked to immune dysfunction. It was reported that sgp120 binding to CD4 on uninfected bystander CD4 + T cells sensitizes them to antibody-dependent cellular-cytotoxicity (ADCC) mediated by non-neutralizing antibodies present in PLWH plasma. Using three independent PLWH cohorts, we observed that non-neutralizing anti-cluster A antibodies are negatively associated with CD4 + T cell counts. Anti-CD4BS antibodies blocked the coating of uninfected bystander cells by sgp120, thereby preventing their elimination by ADCC. Supporting a protective role of anti-CD4BS antibodies, PLWH having these antibodies didn't show a negative association between CD4 T cell counts and anti-cluster A. Our results reveal that anti-cluster A antibodies are associated with immune dysfunction in PLWH and anti-CD4BS antibodies might have a beneficial impact in these individuals.

Biobanking plays a crucial role in promptly generating effective solutions to combat emerging infectious diseases. In direct response to the COVID-19 crisis, Quebec established the "Biobanque qu & eacute;b & eacute;coise de la COVID-19" (BQC19) in March 2020. BQC19 swiftly amassed comprehensive demographic and clinical data and biosamples, from individuals across the province seeking care at participating hospitals and outpatient clinics. This article underscores the transformative potential of BQC19, which has thousands of digitized demographics and clinical records, biosamples from various stages of the pandemic, and provides digital access to the results of numerous multi-omic analyses. By advanced handling and analytical approaches to large sets of genomic, transcriptomic, metabolomic and proteomic data, BQC19 provides a platform to investigate diagnostic and prognostic biomarkers and explore patient stratification for a more personalized approach. Through BQC19, we examine the pivotal role of biobanks in deciphering the complexities of COVID-19 and their capacity to enhance readiness for future infectious threats. BQC19's dynamic framework, encompassing participating hospitals, clinics, research institutions, core analysis laboratory data, and a network of Canadian and international medical professionals and researchers, exemplifies its versatility. With standardized protocols, secure data management, ethical guidelines and community engagement, BQC19 stands as a beacon for proactive research on emerging diseases. Les biobanques sont essentielles au d & eacute;veloppement d'innovations rapides et efficaces pour lutter contre les maladies infectieuses & eacute;mergentes. En r & eacute;ponse & agrave; la pand & eacute;mie de COVID-19, une biobanque prospective ax & eacute;e sur la maladie, la Biobanque qu & eacute;b & eacute;coise de la COVID-19 (BQC19), a & eacute;t & eacute; cr & eacute;& eacute;e au Qu & eacute;bec en mars 2020, parall & egrave;lement & agrave; plusieurs autres lanc & eacute;es au Canada. La BQC19 a recueilli les donn & eacute;es d & eacute;mographiques et cliniques ainsi que les & eacute;chantillons biologiques de nombreuses personnes consentantes qui ont visit & eacute; les h & ocirc;pitaux et les cliniques externes associ & eacute;s & agrave; la BQC19 & agrave; travers la province. Nous pr & eacute;sentons ici comment, en pleine pand & eacute;mie, il a & eacute;t & eacute; possible d'assembler des milliers de donn & eacute;es et d'& eacute;chantillons biologiques pr & eacute;lev & eacute;s & agrave; plusieurs moments, pr & eacute;coces et tardifs, ainsi qu'un grand nombre d'analyses multi-omique r & eacute;alis & eacute;es par la BQC19, afin de cr & eacute;er une plateforme id & eacute;ale pour l'& eacute;tude de la COVID-19. La BQC19 est un parfait exemple d & eacute;montrant l'importante contribution des biobanques & agrave; la compr & eacute;hension des maladies telle la COVID-19 et leur potentiel & agrave; contribuer & agrave; la pr & eacute;paration aux futurs d & eacute;fis pand & eacute;miques. La BQC19 offre un cadre polyvalent pour l'& eacute;tude des futures maladies & eacute;mergentes gr & acirc;ce & agrave; son r & eacute;seau d'h & ocirc;pitaux, de cliniques et d'& eacute;tablissements de recherche en sant & eacute;, & agrave; ses laboratoires d'analyse de base, aux professionnels de la sant & eacute; et aux chercheurs canadiens et internationaux participants, & agrave; ses protocoles op & eacute;rationnels normalis & eacute;s, & agrave; ses plateformes et outils de gestion des donn & eacute;es s & eacute;curis & eacute;s, & agrave; ses protocoles & eacute;thiques et & agrave; ses politiques de consentement ainsi qu'& agrave; ses activit & eacute;s de sensibilisation en milieu rural et & agrave; ses liens avec la communaut & eacute;.