Controlled HIV-HCV Viremia and Immune-Reconstitution are Associated with Slow Progression of Liver Disease in Co-infected Hemophilic Patients After 30 Years of Follow-Up

Introduction and aim: Controversial results have been reported about the progressionof liver disease in HIV-HCV coinfected populations. The purpose of this study is to assesslong-term liver disease progression in a group of coinfected patients with hemophilia.1.2. Materials and Methods: From 1995 to 2015, liver disease was assessed through enzymelevels, platelet counts, Hepatitis C and HIV viral loads (VL), and CD4+T cell counts. Evolution of the APRI liver index was used to estimate hepatic disease (APRI > 1.0 indicatingsevere fibrosis).1.3. Results: 2005-2015 proportional liver-related mortality was below 17% while AIDSand other causes including hemorrhagic events reached 42% each. APRI index >1.0 wasfound in 3 of 32 (9%) patients alive, showing significant liver disease after more than 30years of infection. Analyzing the evolution of liver disease markers, liver enzymes increasedsignificantly only in those patients with detectable HIV and /or HCV VL (for AST and ALT,p<0.0001; for GGT, p=0.001). HIV suppression and reconstitution of CD4+T cell countswere required to achieve HCV eradication. Through multivariate logistic regression, pre ART(pre-antiretroviral therapy) HIV VL was associated with the development of liver fibrosis(OR=4.755; IC95: 1.057 21.387) and with altered liver enzyme values (OR=4.091; IC95:1.293 ? 12.947). No persistent increase in enzyme levels or APRI index was observed in thegroup controlling HIV and HCV replication and adequate immune recovery.1.4. Conclusions: The suppression of both viruses, HIV and HCV, together with adequateimmune recovery is associated with minimal or slow progression of liver disease.Fil: Badano, Maria Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Monzani, María Cecili. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aloisi Zavala, Natalia Andrea. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Gualtieri, Ariel Félix. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Corti, Marcelo. Fundacion de la Hemofilia; ArgentinaFil: Parodi, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pinto, Tezanos. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Primiani, Laura. Fundacion de la Hemofilia; ArgentinaFil: Bracco, M. M. E. D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Chuit, Roberto. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Epidemiológicas; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2

SARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina. Seroconversion rates in unexposed subjects after the first and second doses were 40 % and 100 %, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p < 0.0001). The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p = 0.005). A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p = 0.008). Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p < 0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naïve subjects by two doses of the vaccine (p < 0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects. Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels. Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.Fil: Badano, Maria Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Keitelman, Irene Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pereson Moschen, Matias Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Aloisi, Natalia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Colado, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ortiz Wilczyñski, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Castillo, Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Wigdorovitz, Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Elizalde de Bracco, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fink, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Chuit, Roberto. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Epidemiológicas; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

MHC class II–restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell–mediated autoimmunity

Although plasmacytoid dendritic cells (pDCs) express major histocompatibility complex class II (MHCII) molecules, and can capture, process, and present antigens (Ags), direct demonstrations that they function as professional Ag-presenting cells (APCs) in vivo during ongoing immune responses remain lacking. We demonstrate that mice exhibiting a selective abrogation of MHCII expression by pDCs develop exacerbated experimental autoimmune encephalomyelitis (EAE) as a consequence of enhanced priming of encephalitogenic CD4+ T cell responses in secondary lymphoid tissues. After EAE induction, pDCs are recruited to lymph nodes and establish MHCII-dependent myelin-Ag–specific contacts with CD4+ T cells. These interactions promote the selective expansion of myelin-Ag–specific natural regulatory T cells that dampen the autoimmune T cell response. pDCs thus function as APCs during the course of EAE and confer a natural protection against autoimmune disease development that is mediated directly by their ability to present of Ags to CD4+ T cells in vivo

Influence of Hepatitis C virus coinfection on immune reconstitution in HIV subjects

Despite successful HIV suppression by antiretroviral treatment (ART), immune activation may persist in HIV patients, contributing to an impaired immunological reconstitution and disease progression. Information regarding Hepatitis C virus (HCV) coinfection as a factor that accounts for immune activation in HIV subjects remains unclear. Furthermore, most studies have been carried out considering HIV/HCV patients as a whole, without taking into account the presence or absence of liver damage. Therefore, it is unknown if HCV and/or its liver-related disease could act as two independent factors contributing to the immune activation. In this study, we investigated the presence of immune activation in a cohort of 50 HIV/HCV patients by measuring cytokine levels, CD4+ T-cell counts and CD4/CD8 ratios. Six patient groups were defined according to HIV viral load, HCV status, and liver disease to assess the impact of each of these factors on immune activation and reconstitution in HIV/HCV patients. Only subjects with controlled HIV infection and cleared HCV displayed immunological parameters within normal ranges. The mere presence of HCV contributes to immune activation leading to an inappropriate immunological reconstitution. This state exacerbates in the presence of HCV-associated liver disease. Our results suggest that ART is not enough to suppress immune activation in the context of HIV/HCV coinfection, since both HCV and its liver-related disease would contribute to the immune activation. Given that immune activation worsens immunological reconstitution and clinical status, these results support the priority of HCV treatment in HIV/HCV patients and suggest the monitoring of their liver status.Fil: Badano, Maria Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Parodi, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Aloisi Zavala, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Corti, Marcelo. Fundación de la Hemofilia; ArgentinaFil: Elizalde de Bracco, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

TNF-α Levels in Respiratory Samples Are Associated with SARSCoV- 2 Infection

The aim of this study was to evaluate concentrations of IL-6 and TNF-α in swab samples from individuals with symptoms compatible with COVID-19 and analyze their association with SARS-CoV-2 genome presence.The study was conducted on 127 combined nasopharyngeal and oropharyngeal swabs, referred to the laboratory for detection of SARS-CoV-2. Cytokine levels of symptomatic individuals with detectable (n = 52) or undetectable (n = 33) SARS-CoV-2 were measured. A group consisting of asymptomatic individuals and negative for SARS-CoV-2 genome (n = 42) were included to obtain cytokines? normal range. Concentrations of TNF-α (standard curve range: 0 to 500 pg/mL) and IL-6 (standard curve range: 0 to 300 pg/mL) in swabs were determined using commercial reagents based on enzyme linked immunosorbent assay (BD-Biosciences).TNF-α levels were higher in SARS-CoV-2 (+) symptomatic group (mean: 16 pg/mL, median value: 5.88 (5 to 172.1) pg/mL) compared with SARS-CoV-2 (?) symptomatic individuals (mean: 7.6 pg/mL, median: 5.00 (5 to 69.9) pg/mL) (P = 0.0009) (Fig. 1Bi). IL-6 was increased in some individuals with no significant difference between groups (mean: 33.95 pg/mL, median: 5.40 (5 to 467) pg/mL and for SARS-CoV-2 (?) mean: 30.4 pg/mL, median: 6.07 (5 to 466.6) pg/mL) (Fig. 1Bii). Considering a threshold value of 10 pg/mL for TNF-α, individuals with SARS-CoV-2 (+) were six times more likely to display increased levels of TNF-α (OR = 5.7; P = 0.006; 95% CI = 1,551 to 19,11). A correlation between TNF-α or IL-6 levels and viral load (Ct) was not found. Furthermore, age and gender were not related with cytokine concentration among SARS-CoV-2 (+) group. Focusing only on hospitalized patients, individuals with viral genome presence showed increased TNF-α values (mean: 18.7 pg/mL, median 5 pg/mL; 5 to 172.2) compared with those with absent SARS-CoV-2 genome (mean: 7.95 pg/mL, median 5 [5 to 65] pg/mL) (P = 0.028).Our findings, evaluating the concentration of TNF and IL-6 at the entry site of SARS-CoV-2, highlight the pleiotropic role of IL-6 in local inflammation process and show that TNF-α could contribute to disease evolution prognosis as a biomarker. Measurement of TNF-α in nasopharyngeal swabs at diagnosis could identify those individuals that may benefit from immunomodulatory and cytokine inhibiting therapies.Fil: Pereson Moschen, Matias Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquÍmica. Instituto de Investigaciones En Bacteriología y Virología Molecular (IBaViM); ArgentinaFil: Badano, Maria Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Aloisi Zavala, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Chuit, Roberto. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Epidemiológicas; ArgentinaFil: de Bracco, M. M. E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

SARS-CoV-2 Breakthrough Infections after Third Doses Boost IgG Specific Salivary and Blood Antibodies

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase in systemic antibodies, which were higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose three occurred and boosted antibody levels in the salivary compartment. These results suggest that current vaccination strategies against COVID-19 should be improved. Results also showed that determination of salivary antibodies against SARS-CoV-2 could be a valuable tool in disease prevalence studies, for the follow-up of vaccinated individuals, and to assist vaccination strategies against COVID-19, especially in settings where blood sampling cannot be fulfilled.Fil: Badano, Maria Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Pereson Moschen, Matias Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular; ArgentinaFil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Keitelman, Irene Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Aloisi Zavala, Natalia Andrea. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Chuit, Roberto. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Epidemiológicas; ArgentinaFil: de Bracco, María M. E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fink, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentin