The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis.

Background and Objectives: Sepsis involves a dysregulated host response, characterized by simultaneous immunosuppression and hyperinflammation. Initially, there is the release of pro-inflammatory factors and immune system dysfunction, followed by persistent immune paralysis leading to apoptosis. This study investigates sepsis-induced apoptosis and its pathways, by assessing changes in PD-1 and PD-L1 serum levels, CD4+ and CD8+ T cells, and Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) severity scores. Materials and Methods: This prospective, observational, single-centre study enrolled 87 sepsis patients admitted to the intensive care unit at the County Emergency Clinical Hospital in Târgu Mureș, Romania. We monitored the parameters on day 1 (the day sepsis or septic shock was diagnosed as per the Sepsis-3 Consensus) and day 5. Results: Our study found a statistically significant variation in the SOFA score for the entirety of the patients between the studied days (p = 0.001), as well as for the studied patient groups: sepsis, septic shock, survivors, and non-survivors (p = 0.001, p = 0.003, p = 0.01, p = 0.03). On day 1, we found statistically significant correlations between CD8+ cells and PD-1 (p = 0.02) and PD-L1 (p = 0.04), CD4+ and CD8+ cells (p < 0.0001), SOFA and APACHE II scores (p < 0.0001), and SOFA and APACHE II scores and PD-L1 (p = 0.001 and p = 0.01). On day 5, we found statistically significant correlations between CD4+ and CD8+ cells and PD-L1 (p = 0.03 and p = 0.0099), CD4+ and CD8+ cells (p < 0.0001), and SOFA and APACHE II scores (p < 0.0001). Conclusions: The reduction in Th CD4+ and Tc CD8+ lymphocyte subpopulations were evident from day 1, indicating that apoptosis is a crucial factor in the progression of sepsis and septic shock. The increased expression of the PD-1/PD-L1 axis impairs costimulatory signalling, leading to diminished T cell responses and lymphopenia, thereby increasing the susceptibility to nosocomial infections.

Lymphocyte Subsets in Cervicovaginal Lavage Specimens of HIV-Infected Women: A Surrogate Risk Marker of HPV-Associated Cervical Lesions.

INTRODUCTION: To better understand the role of mucosa immunity in the development of cervical carcinoma in HIV infection, cervical lymphocyte subsets were characterized in HIV+ and HIV- women, as well as their relation to HPV-associated cervical lesions. METHODS: Eighty-three (52 HIV+, 31 HIV-) cell suspensions of cervicovaginal lavage (CVL) and 52 HIV+ peripheral blood (PB) samples were assessed by flow cytometry to evaluate lymphoid populations. High-risk (HR) HPV was assessed in liquid-based cytology and HIV mRNA in PB in the same patients. RESULTS: Cervical CD4+ T cells and CD4+/CD8+ ratio were decreased (p < 0.0001) and cervical CD8+ T cells were increased (p = 0.0080) in HIV+ women. These patients had lower CD4+ T-cell percentages in CVL compared to PB (p = 0.0257), and the opposite was true for CD8+ T cells (p = 0.0104). They also had a higher prevalence of high-grade squamous intraepithelial lesions (SILs) with an increased prevalence of HR HPV. Cervical CD8+ T cells were increased in HR HPV+ patients (p = 0.0300) and related to higher prevalence of SILs (p = 0.0001). DISCUSSION/CONCLUSION: Cervical lymphoid populations can be characterized by flow cytometry, showing a distinct cervical T-cell compartment in HIV+ women. This may represent a surrogate risk marker of HPV-associated cervical lesions in this population and prompt further research on this subject, contributing to improving patients' management.

CD8+ Lymphocyte Infiltration Is a Specific Feature of Colitis Induced by Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICPIs) have revolutionized cancer therapy, although immune-related adverse events (irAEs) remain a serious issue. The clinical characteristics of colitis induced by ICPIs are very similar to inflammatory bowel disease. Recently, cluster of differentiation 8 positive (CD8+) lymphocyte infiltration into organs has been associated with the onset of irAEs. The present study compared the histological infiltration of CD8+ lymphocytes in irAE colitis with that in other colitis. METHODS: Newly diagnosed and untreated patients were retrospectively enrolled. Biopsy specimens were obtained from endoscopic areas of high inflammation for immunohistochemical analysis of the number of cluster of differentiation 4 positive (CD4+) and CD8+ lymphocytes in the high-powered microscopic field with the most inflammation. RESULTS: A total of 102 patients [12 with irAE colitis, 37 with ulcerative colitis (UC), 22 with Crohn's disease (CD), and 31 with ischemic colitis (IC)] were analyzed. In irAE colitis, CD8+ lymphocyte infiltration was significantly greater than that of CD4+ lymphocytes (p < 0.01). The amount of CD8+ lymphocyte infiltration was significantly higher in irAE colitis than in UC (p < 0.05), CD (p < 0.05), and IC (p < 0.01). The CD8+/CD4+ ratio was also significantly higher in irAE colitis (p < 0.01 versus UC, CD, and IC, respectively). The optimal cutoff CD8+/CD4+ ratio for diagnosing irAE colitis was 1.17 (sensitivity 83%, specificity 84%). The optimal cutoff number of CD8+ lymphocytes for diagnosing irAE colitis was 102 cells per high-power field (sensitivity 75%, specificity 81%). CONCLUSIONS: Greater CD8+ lymphocyte infiltration and a higher CD8+/CD4+ ratio may be simple and useful biomarkers to distinguish irAE colitis from other forms of colitis.

Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry.

Background and Objectives: There is no biomarker to predict lithium response. This study used CellPrint™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4+ lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). Materials and Methods: Symptomatic patients with BD type I or II received lithium (serum level ≥ 0.6 mEq/L) for 16 weeks. Patients were assessed with standard rating scales and divided into two groups, responders (≥50% improvement from baseline) and non-responders. Twenty-eight intracellular proteins in CD4+ lymphocytes and monocytes were analyzed with CellPrint™, an enhanced flow cytometry procedure. Data were analyzed for differences in protein expression levels. Results: The intent-to-treat sample included 13 lithium-responders (12 blood samples before treatment and 9 after treatment) and 11 lithium-non-responders (11 blood samples before treatment and 4 after treatment). No significant differences in expression between the groups was observed prior to lithium treatment. After treatment, the majority of analytes increased expression in responders and decreased expression in non-responders. Significant increases were seen for PDEB4 and NR3C1 in responders. A significant decrease was seen for NR3C1 in non-responders. Conclusions: Lithium induced divergent directionality of protein expression depending on the whether the patient was a responder or non-responder, elucidating molecular characteristics of lithium responsiveness. A subsequent study with a larger sample size is warranted.

Mould-reactive T cells for the diagnosis of invasive mould infection-A prospective study.

Invasive mould infections (IMI) in immunocompromised patients are difficult to diagnose. Early and targeted treatment is paramount, but minimally invasive tests reliably identifying pathogens are lacking. We previously showed that monitoring pathogen-specific CD4+T cells in peripheral blood using upregulation of induced CD154 positive lymphocytes can be used to diagnose acute IMI. Here, we validate our findings in an independent patient cohort. We stimulated peripheral blood cells from at-risk patients with Aspergillus spp. and Mucorales lysates and quantitated mould-reactive CD4/CD69/CD154 positive lymphocytes via flow cytometry. Mould-reactive lymphocytes were quantitated in 115 at-risk patients. In 38 (33%) patients, the test was not evaluable, mainly due to low T cell counts or non-reactive positive control. Test results were evaluable in 77 (67%) patients. Of these, four patients (5%) had proven IMI and elevated mould-reactive T cell signals. Of 73 (95%) patients without proven IMI, 59 (81%) had mould-reactive T cell signals within normal range. Fourteen (19%) patients without confirmed IMI showed elevated T cell signals and 11 of those received antifungal treatment. The mould-reactive lymphocyte assay identified presence of IMI with a sensitivity of 100% and specificity of 81%. The mould-reactive lymphocyte assay correctly identified all patients with proven IMI. Assay applicability is limited by low T cell counts during bone marrow suppression. The assay has the potential to support diagnosis of invasive mould infection to facilitate tailored treatment even when biopsies are contraindicated or cultures remain negative.

Detection of Small Subsets of CD4+ Lymphocytes with SmartFlare Nanoprobes.

SmartFlare technology allows detection of mRNA in single living cells. We studied the possibility of using SmartFlare nanoprobes for detection of small subsets of CD4+ lymphocytes. It was found that SmartFlare allows detection of transcriptional master regulators of major CD4+T helper subsets in living human lymphocytes. Nanoprobes labeled with Cy5 fluorophore were better detected by flow cytometry than nanoprobes labeled with Cy3. Appropriate time of lymphocyte incubation with SmartFlare probes was 24 h.

Clinical, Virusological and Immunological characteristics of hospitalised HIV-infected patients.

AIM: The primary objective of this study was to describe clinical, virusological and immunological characteristics of hospitalised HIV--infected patients, who had different stages of the disease. MATERIALS AND METHODS: This study was conducted at Moscow Infectious Diseases Hospital №2 in 2012-2015. We have clinically observed 5485 HIV-infected patientsand studied their clinical histories [age: 25-45 (87%), men - 3998 (72.9%), women - 1487 (27.1%)]. 593 (10.8%) have died. We have tested plasma and liquor HIV RNA viral load, immune status, number of viral DNA copies in blood, liquor, lavage, pleural fluid, large intestinal and esophagus biopsies and other materials. Statistica v. 10.0 and SPSS v. 20 were used for statistical analysis. RESULTS: Сlinical state of HIV-infected hospitalised patients has been described and the results of quantitive determination of HIV RNA in blood and liquor, absolute and relative CD4+ and CD8+ T-lymphocytes concentrations and immunoregulatory index in patients in various disease stages, including patients on antiretroviral therapy (ART) have been presented. Statistically significant correlation between blood and liquor HIV RNA load as well as between viral load and cellular immune markers in hospitalised HIV-infected patients has been found.

[Clinical, Virusological and Immunological characteristics of hospitalised HIV-infected patients].

AIM: The primary objective of this study was to describe clinical, virusological and immunological characteristics of hospitalised HIV-infected patients, who had different stages of the disease. MATERIALS AND METHODS: This study was conducted at Moscow Infectious Diseases Hospital №2 in 2012-2015. We have clinically observed 5485 HIV-infected patientsand studied their clinical histories [age: 25-45 (87%), men - 3998 (72.9%), women - 1487 (27.1%)]. 593 (10.8%) have died. We have tested plasma and liquor HIV RNA viral load, immune status, number of viral DNA copies in blood, liquor, lavage, pleural fluid, large intestinal and esophagus biopsies and other materials. Statistica v. 10.0 and SPSS v. 20 were used for statistical analysis. RESULTS AND CONCLUSION: Clinical state of HIV-infected hospitalised patients has been described and the results of quantitive determination of HIV RNA in blood and liquor, absolute and relative CD4+ and CD8+ T-lymphocytes concentrations and immunoregulatory index in patients in various disease stages, including patients on antiretroviral therapy (ART) have been presented. Statistically significant correlation between blood and liquor HIV RNA load as well as between viral load and cellular immune markers in hospitalised HIV-infected patients has been found.

Methylation profiles in peripheral blood CD4+ lymphocytes versus brain: The relation to Alzheimer's disease pathology.

INTRODUCTION: We investigated the change in DNA methylation in peripheral blood CD4+ lymphocytes over time, examined the relation between CD4+ lymphocytes and brain methylation, and compared their associations with AD pathology. METHODS: Genome-wide methylation was measured three times in 41 older persons using Illumina Infinium HumanMethylation450 array. The two CD4+ lymphocytes measures were at study baseline and proximate to death. Brain tissue came from frozen dorsolateral prefrontal cortex. RESULTS: Global methylation features were conserved across tissue. At individual CpG sites, methylation level was concordant between the two CD4+ lymphocytes but more diffuse between CD4+ lymphocytes and brain. Previous associations of brain methylation with neuritic plaques at target methylation sites were not replicated in CD4+ lymphocytes. DISCUSSION: There is no strong evidence of change in CD4+ lymphocytes methylation among older persons over an average of 7.5 years. Methylation associations with AD pathology found in neocortex are not directly reflected in CD4+ lymphocytes.

Pollution of mycological surfaces in hospital emergency departments correlates positively with blood NKT CD3(+) 16(+) 56(+) and negatively with CD4(+) cell levels of their staff.

The aim of the present study was the assessment of the putative influence of yeast and filamentous fungi in healthcare and control (office) workplaces (10 of each kind) on immune system competence measured by NK (natural killer), CD4(+), and NKT (natural killer T lymphocyte) cell levels in the blood of the personnel employed at these workplaces. Imprints from floors and walls were collected in winter. The blood was taken in spring the following year, from 40 men, 26 to 53 years old, healthcare workers of hospital emergency departments (HED), who had been working for at least five years in their current positions, and from 36 corresponding controls, working in control offices. Evaluation of blood leukocyte subpopulations was done by flow cytometry. The qualitative analysis of the surface samples revealed a prevalence of strains belonging to Aspergillus spp. and Penicillium spp. genus. There was no statistically significant difference between the level of NKT; however, the percentage of NK cells was lower in the blood of HED workers than in the blood of offices personnel. Spearman analysis revealed the existence of positive correlation (r = 0.4677, p = 0.002) between the total CFU/25 cm(2) obtained by imprinting method from walls and floors of HED and the percentage of NKT (CD3(+)16(+)56(+)) lymphocytes collected from the blood of their personnel, and negative correlation (r = -0. 3688, p = 0.019) between this parameter of fungal pollution and the percentage of CD4(+) lymphocytes in the blood of HED staff. No other correlations were found.

The CD4(+) AT2R(+) T cell subpopulation improves post-infarction remodelling and restores cardiac function.

Myocardial infarction (MI) is a major condition causing heart failure (HF). After MI, the renin angiotensin system (RAS) and its signalling octapeptide angiotensin II (Ang II) interferes with cardiac injury/repair via the AT1 and AT2 receptors (AT1R, AT2R). Our study aimed at deciphering the mechanisms underlying the link between RAS and cellular components of the immune response relying on a rodent model of HF as well as HF patients. Flow cytometric analyses showed an increase in the expression of CD4(+) AT2R(+) cells in the rat heart and spleen post-infarction, but a reduction in the peripheral blood. The latter was also observed in HF patients. The frequency of rat CD4(+) AT2R(+) T cells in circulating blood, post-infarcted heart and spleen represented 3.8 ± 0.4%, 23.2 ± 2.7% and 22.6 ± 2.6% of the CD4(+) cells. CD4(+) AT2R(+) T cells within blood CD4(+) T cells were reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients. Moreover, we characterized CD4(+) AT2R(+) T cells which expressed regulatory FoxP3, secreted interleukin-10 and other inflammatory-related cytokines. Furthermore, intramyocardial injection of MI-induced splenic CD4(+) AT2R(+) T cells into recipient rats with MI led to reduced infarct size and improved cardiac performance. We defined CD4(+) AT2R(+) cells as a T cell subset improving heart function post-MI corresponding with reduced infarction size in a rat MI-model. Our results indicate CD4(+) AT2R(+) cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof.

A genome-wide survey of CD4(+) lymphocyte regulatory genetic variants identifies novel asthma genes.

BACKGROUND: Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. OBJECTIVE: We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4(+) lymphocytes for association with asthma. METHODS: eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. RESULTS: Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3/GSDMB variants with asthma (combined P = 2.9 × 10(-8)). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 (FADS2; P = .002), N-acetyl-α-D-galactosaminidase (NAGA; P = .0002), and Factor XIII, A1 (F13A1; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4(+) lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. CONCLUSIONS: Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma.

Adaptive response in hepatitis B virus infection.

Hepatitis B virus (HBV) is a major cause of acute and chronic liver inflammation worldwide. The immune response against the virus represents a key factor in determining infection outcome, in terms of both viral clearance and the perpetuation of liver damage. Significant advances have recently been achieved regarding the functions of antiviral CD8+ T cells, leading to a better understanding of their abnormalities during chronic infection as well as the pathways to be manipulated to reverse the immune impairment of chronic infection. In this review, we aimed to analyse the patterns of adaptive immunity that develop during acute infection and the profiles in chronic infection. In addition to CD8+ T cells, which are the best-described subset to date, we reviewed and commented on the direct and indirect roles of CD4+ T cells and B cells.

B and T cells: (Still) the dominant orchestrators in autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a severe hepatopathy characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological appearance of interface hepatitis. Liver damage in AIH is initiated by the presentation of a liver autoantigen to uncommitted Th0 lymphocytes, followed by a cascade of effector immune responses culminating with the production of inflammatory cytokines, activation of cytotoxic cells and subsequent hepatocyte injury. B cells actively participate in AIH liver damage by presenting autoantigens to uncommitted T lymphocytes. B cells also undergo maturation into plasma cells that are responsible for production of immunoglobulin G and autoantibodies, which mediate antibody dependent cell cytotoxicity. Perpetuation of effector immunity with consequent progression of liver damage is permitted by impairment in regulatory T cells (Tregs), a lymphocyte subset central to the maintenance of immune homeostasis. Treg impairment in AIH is multifactorial, deriving from numerical decrease, reduced suppressive function, poor response to IL-2 and less stable phenotype. In this review, we discuss the role of B and T lymphocytes in the pathogenesis of AIH. Immunotherapeutic strategies that could limit inflammation and halt disease progression while reconstituting tolerance to liver autoantigens are also reviewed and discussed.

Corrigendum: Experimental validation of immunogenic SARS-CoV-2 T cell epitopes identified by artificial intelligence.

[This corrects the article DOI: 10.3389/fimmu.2023.1265044.].

Scrutinizing Clinical Biomarkers in a Large Cohort of Patients with Lyme Disease and Other Tick-Borne Infections.

Standard clinical markers can improve tick-borne infection (TBI) diagnoses. We investigated immune and other clinical biomarkers in 110 patients clinically diagnosed with TBIs before (T0) and after antibiotic treatment (T2). At T0, both the initial observation group and patients without seroconversion for tick-borne pathogens exhibited notably low percentages and counts of CD3 percentage (CD3%), CD3+ cells, CD8+ suppressors, CD4 percentage (CD4%), and CD4+ helper cells, with the latter group showing reductions in CD3%, CD3+, and CD8+ counts in approximately 15-22% of cases. Following treatment at the T2 follow-up, patients typically experienced enhancements in their previously low CD3%, CD3+ counts, CD4%, and CD4+ counts; however, there was no notable progress in their low CD8+ counts, and a higher number of patients presented with insufficient transferrin levels. Moreover, among those with negative serology for tick-borne infections, there was an improvement in low CD3% and CD3+ counts, which was more pronounced in patients with deficient transferrin amounts. Among those with CD57+ (n = 37) and CD19+ (n = 101) lymphocyte analysis, 59.46% of patients had a low CD57+ count, 14.85% had a low CD19 count, and 36.63% had a low CD19 percentage (CD19%). Similar findings were observed concerning low CD57+, CD19+, and CD19% markers for negative TBI serology patients. Overall, this study demonstrates that routine standard clinical markers could assist in a TBI diagnosis.

Proteinase-activated receptor-2 activation participates in allergic sensitization to house dust mite allergens in a murine model.

BACKGROUND: Many aeroallergens contain proteinase activity and are able to induce allergic sensitization when presented to mucosal surfaces. Some of these allergens activate proteinase-activated receptor-2 (PAR2 ). OBJECTIVE: To determine the role of PAR2 activation in a murine house dust mite (HDM) allergy model. METHODS: We sensitized and challenged PAR2 -deficient mice with HDM, and examined allergic outcomes compared to wild-type animals. To focus on the role of PAR2 in allergic sensitization, we administered a PAR2 blocking antibody to wild-type animals during the sensitization phase and examined the outcomes immediately after sensitization or following subsequent allergen challenge. RESULTS: We found PAR2 -deficient mice sensitized and challenged with HDM failed to develop airway inflammation, did not produce HDM-specific IgG1 and had less IL-4 mRNA in the lungs than wild-type animals. Prevention of PAR2 activation during sensitization in wild-type mice diminished the levels of Th2 mediators, including IL-4, IL-5 and IL-13, in the lungs. Blocking PAR2 during the sensitization phase also led to decreased manifestations of allergic disease, including airway hyperresponsiveness (AHR) and airway inflammation following subsequent allergen challenge. HDM-induced proliferation of splenocytes obtained from animals sensitized in the presence of PAR2 antibody was reduced relative to those that did not receive antibody. The effect of PAR2 blockade could be transferred to naïve mice through splenic CD4(+) T cells from sensitized mice. CONCLUSIONS AND CLINICAL RELEVANCE: PAR2 activation plays a key role during the sensitization phase of our HDM allergy model, leading to increased lung cytokine production and augmented lung reactivity. PAR2 activation is a common mechanism for sensitization to a wide variety of allergens and is therefore a potential pharmacological target to prevent allergy.

Correlation between stromal Th and Tc lymphocytes and PD-L1 expression in early breast cancer tumors.

INTRODUCTION: Prognostic and predictive value of PD-L1 as a biomarker in breast cancer remains controversial. While some studies suggest its association with negative prognostic parameters, others reported a highly significant association between PD-L1 expression and tumor-infiltrating lymphocytes, which are known to be an independent favorable prognostic factor. The aim of present study is to examine the relationship between immune response markers and PD-L1 expression in early breast cancer. MATERIAL AND METHODS: Immunohistochemical expression of PD-L1, along with density and composition of stromal lymphocytic infiltrate and peritumoral lymphoid aggregates was analyzed in 95 samples of invasive breast cancer. RESULTS: A strong positive correlation between PD-L1 expression and the density of stromal lymphocytic infiltrate and peritumoral lymphoid aggregates was identified and a cut-off value of 53% coverage of tumor stroma by lymphocytes, with which PD-L1 positivity can be predicted with excellent diagnostic accuracy, was determined for the first time using statistical methods. Additionally, PD-L1 positivity was observed significantly more often in tumors with higher absolute number of both CD4 and CD8 T-lymphocytes in the stromal infiltrate. No significant correlation with molecular subtype of breast cancer was found. CONCLUSIONS: Our results indicate that the density of stromal lymphocytic infiltrate might be a better predictor of PD-L1 positivity in early breast cancer than the molecular subtype and that the key to the optimization of PD-L1 as a biomarker in breast cancer lies in its interpretation in the context of other immune response markers.

Particular Aspects Related to CD4+ Level in a Group of HIV-Infected Patients and Associated Acute Coronary Syndrome.

People living with HIV infection are at high risk for cardiovascular events due to inflammation and atherosclerosis. Also, some antiretroviral therapies may contribute to the risk of cardiovascular complications. Immune status is highly dependent on the level of lymphocyte T helper CD4+. There are data suggesting that immune status and CD4+ cell count may be involved in the development of cardiovascular complications in these patients. Our study is longitudinal and retrospective and included a total number of 50 patients with HIV infection associated with acute coronary syndrome, divided into two subgroups based on the nadir of CD4+ cells. This study analyzes the relationship between the immune status of HIV patients, assessed by the nadir of the CD4+ T-cell count, and the outcome of these patients. Also, secondary endpoints were the assessment of the magnitude of coronary lesions and of thrombotic and bleeding risk assessed by specific scores. Clinical and biological parameters and also the extension and complexity of coronary lesions were assessed. Although patients with poor immune status had more complex coronary lesions and increased operative risk and bleeding risk at one year, this was not associated with significant differences in major adverse cardiac and cerebrovascular events at the 30-day and 1-year outcomes.

Pre-existing immunity to SARS-CoV-2 before the COVID-19 pandemic era in Cameroon: A comparative analysis according to HIV-status.

Background: The lower burden of COVID-19 in tropical settings may be due to preexisting cross-immunity, which might vary according to geographical locations and potential exposure to other pathogens. We sought to assess the overall prevalence of SARS-CoV-2 antibodies and determine SARS-CoV-2 seropositivity according to HIV-status before the COVID-19 pandemic era. Methods: A cross-sectional and comparative study was conducted at the Chantal BIYA International Reference Centre (CIRCB) on 288 stored plasma samples (163 HIV-positive versus 125 HIV-negative); all collected in 2017-2018, before the COVID-19 pandemic era. Abbott Panbio™ COVID-19 IgG/IgM assay was used for detecting SARS-CoV-2 immunoglobulin G (IgG) and M (IgM). Among people living with HIV (PLHIV), HIV-1 viral load and TCD4 cell count (LTCD4) were measured using Abbott Real Time PCR and BD FACSCalibur respectively. Statistical analyses were performed, with p<0.05 considered statistically significant. Results: The median [IQR] age was 25 [15-38] years. Overall seropositivity to SARS-CoV-2 antibodies was 13.5% (39/288) of which 7.3% (21) was IgG, 7.3% (21) IgM and 1.0% (3) IgG/IgM. According to HIV-status in the study population, SARS-CoV-2 seropositivity was 11.0% (18/163) among HIV-positive versus 16.8% (21/125) among HIV-negative respectively, p=0.21. Specifically, IgG was 6.1% (10/163) versus 8.8% (11/125), p=0.26; IgM was 5.5% (9/163) versus 9.6%, (12/125), p=0.13 and IgG/IgM was 0.6% (1/163) versus 1.6% (2/125) respectively. Among PLHIV, SARS-CoV-2 seropositivity according to CD4 count was 9.2% (≥500 cells/µL) versus 1.8% (200-499 cells/µL), (OR=3.5; p=0.04) and 0.6% (<200 cells/µL), (OR=17.7; p<0.01). According to viral load, SARS-CoV-2 seropositivity was 6.7% (≥40 copies/mL) versus 4.9% (<40 copies/mL), (OR= 3.8; p<0.01). Conclusion: Before COVID-19 in Cameroon, cross-reactive antibodies to SARS-CoV-2 were in circulation, indicating COVID-19 preexisting immunity. This preexisting immunity may contribute in attenuating disease severity in tropical settings like Cameroon. Of relevance, COVID-19 preexisting immunity is lower with HIV-infection, specifically with viral replication and poor CD4-cell count. As poor CD4-count leads to lower cross-reactive antibodies (regardless of viral load), people living with HIV appear more vulnerable to COVID-19 and should be prioritized for vaccination.