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A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection. The durability of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. Lessons from seasonal coronavirus infections in humans show that reinfections can occur within 12 months of initial infection, coupled with changes in levels of virus-specific antibodies.

Achieving functional cure of chronic HBV infection (Hepatitis B surface antigen [HBsAg] clearance, eventually followed by acquisition of anti-hepatitis B surface antigen [Anti-HBs]) in individuals with HIV and HBV infections is a rare event. In this setting, factors related to HBV cure have not yet been fully characterized. HIV-infected individuals with chronic HBV infection enrolled in the French Dat'AIDS cohort (NCT02898987), who started combined antiretroviral (cART)-anti-HBV treatment were retrospectively analyzed for HBsAg loss and Anti-HBs seroconversion. Overall, 1419 naïve-subjects received three different cART-anti-HBV treatment schedule: (1) 3TC or FTC only (n = 150), (2) TDF with or without 3TC or FTC (n = 489) and (3) 3TC or FTC as first line followed by adding/switching to TDF as second line (n = 780). Individuals were followed-up for a median of 89 months (IQR, 56-118). HBV-DNA was < 15 IU/mL in 91% of individuals at the end of the follow-up. Overall, 97 individuals cleared HBsAg (0.7/100 patient-years), of whom, 67 seroconverted for Anti-HBs (0.5/100 patient-years). A high CD4 nadir, a short delay between HBV diagnosis and treatment, a longer time on HBV therapy, an African origin and TDF-based therapy were independent predictors of HBsAg clearance (Probability of odds ratio [OR]>1, >95%) suggested by Bayesian analysis. Also, TDF-based regimen as first line (OR, 3.03) or second line (OR, 2.95) increased rates of HBsAg clearance compared to 3TC or FTC alone, with a 99% probability. HBsAg clearance rate was low in HIV-HBV co-infected cART-anti-HBV treated individuals, but was slightly improved on TDF-based regimen.

Tuberculosis (TB) and HIV co-infections are extensively overlapping, especially in developing countries. HIV infection is known as a major risk factor for the reactivation of latent TB into active TB. Although not fully understood and needs further study, HIV infection might enhance the reactivation of latent TB by breaching immune control mechanisms. We investigated the influence of HIV infection on the cytokine response of LTB-infected individuals. Heparinized venous blood was collected from 40 ART-naïve HIV-infected and 30 HIV-negative healthy controls for LTB screening, plasma collection, and PBMC isolation and stimulation. The level of cytokines in plasma and their production by PBMCs stimulated with purified protein derivative (PPD), staphylococcus enterotoxin B (SEB), or unstimulated PBMCs were analyzed using a cytometric bead array (CBA) assay. PPD-induced IL-2 by PBMCs was higher in LTB-infected groups compared with HIV-negative LTB-negative groups (p = 0.0015). When LTB-infected groups were co-infected with HIV (HIV + LTB + ), the IL-2 (p < 0.0001) and IFN-gamma (p = 0.0144) production by PPD-stimulated PBMCs was reduced. The level of IL-2 (p = 0.0070), IL-6 (p = 0.0054), and TNF-alpha (p = 0.0045) in plasma were lower in HIV + LTB + individuals compared with HIV-negative LTB-positive (HIV - LTB + ) groups. Our findings suggested that HIV co-infection in LTB-positive individuals is associated with the diminished production of PPD-induced Th1 (IFN-gamma and IL-2) cytokines by PBMCs and in the plasma level of IL-2 and proinflammatory cytokines (IL-6 and TNF-alpha).

Hepatitis B core antibody (anti-HBc) is considered the most sensitive serological marker for history of hepatitis B virus (HBV) infection. In a subset of anti-HBc carriers, anti-HBc is present in the absence of hepatitis B surface antigen and hepatitis B surface antibody-a serological pattern known as \"isolated anti-HBc\" (IAHBc). IAHBc has been of clinical interest over the past several years, with growing data to suggest its role as a serological marker for occult HBV infection (OBI). This article reviews the clinical significance and association of IAHBc with hepatitis C virus (HCV) co-infection, risk of HBV reactivation during direct-acting antiviral therapy for HCV as well as immune suppression, and development of hepatocellular carcinoma (HCC). Hepatitis B core-related antigen is also highlighted as an emerging laboratory assay that may identify OBI and predict HCC development in non-cirrhotic patients receiving nucleoside/nucleotide analog therapy.

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) alter lipid and glucose metabolism mediated by cytokines release. Our aim was to assess the evolution in metabolic plasmatic markers of people living with HIV (PLHIV) after HCV elimination either spontaneously or with direct active antivirals (DAAs). Multicenter prospective study of 116 HIV patients: i) HCV chronically infected patients (CHC) = 45; ii) Spontaneous clarifiers (SC) = 36; and iii) HIV control group = 35. HCV-exposed patients were all studied at baseline and 48 weeks after achieving sustained virological response (SVR). Plasma levels of 14 metabolic biomarkers were measured. Differences between groups were evaluated by statistical methods. At baseline, CHC patients showed higher levels of adiponectin, NGAL and sICAM-1, than the control group. After achieving SVR, the CHC group showed a significant decrease in the 3 cytokines that were increased at baseline: adiponectin, NGAL and sICAM. In contrast, there was an increase in cortisol. After the end of the follow-up CHC showed normalization of all measured markers that were increased at baseline. Any changes were observed in the same follow-up period for the SC group. Chronically coinfected HIV + /HCV + patients showed altered levels in lipid and glucose metabolism compared to HIV monoinfected subjects and spontaneous clearers. The elimination of chronic HCV infection by DAAs normalized the metabolism profile except for cortisol that remains increased after reaching RSV compared to levels observed in the HCV-/HIV + group. Spontaneous clarification of HCV did not modify metabolism biomarkers in these patients.

Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a secondary infection while in the intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses. To compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not. Consecutive patients with sepsis with a length of ICU stay greater than 48 hours were prospectively analyzed for the development of ICU-acquired infections. Twenty host response biomarkers reflective of key pathways implicated in sepsis pathogenesis were measured during the first 4 days after ICU admission and at the day of an ICU-acquired infection or noninfectious complication. Of 1,237 admissions for sepsis (1,089 patients), 178 (14.4%) admissions were complicated by ICU-acquired infections (at Day 10 [6-13], median with interquartile range). Patients who developed a secondary infection showed higher disease severity scores and higher mortality up to 1 year than those who did not. Analyses of biomarkers in patients who later went on to develop secondary infections revealed a more dysregulated host response during the first 4 days after admission, as reflected by enhanced inflammation, stronger endothelial cell activation, a more disturbed vascular integrity, and evidence for enhanced coagulation activation. Host response reactions were similar at the time of ICU-acquired infectious or noninfectious complications. Patients with sepsis who developed an ICU-acquired infection showed a more dysregulated proinflammatory and vascular host response during the first 4 days of ICU admission than those who did not develop a secondary infection.

Zika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.

Background & objectives Despite the evidence of population differences in miRNA expression, limited information is available about the expression profile of miRNAs in Indian tuberculosis (TB) patients. The present study aimed to investigate the expression profile of candidate serum exosomal microRNAs in Indian patients with and without HIV-TB coinfection. Methods The pool samples of serum exosomes of study participants (HIV-TB coinfection, extra-pulmonary TB, HIV mono-infection, pulmonary TB) and healthy humans were processed for the isolation of total RNA followed by miRNA analysis using miRCURY LNA human focus PCR panel by real-time PCR. The significantly altered miRNAs were identified using differential expression analysis. The target genes prediction and potential functional analysis of exclusively differentially expressed miRNAs were performed using bioinformatics tools. Results The expression profile of 57, 58, 49 and 11 miRNAs was significantly altered in exosome samples of HIV-TB coinfected, extra-pulmonary TB, HIV mono-infected and pulmonary TB patients compared to healthy controls, respectively. The set of three (hsa-let-7i-5p, hsa-miR-24-3p, hsa-miR-92a-3p), three (hsa-miR-20a-5p, hsa-let-7e-5p, hsa-miR-26a-5p) and four (hsa-miR-21-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, hsa-miR-146a-5p) miRNAs were exclusively significantly differentially expressed in study participants with HIV-TB coinfection, extra-pulmonary TB and pulmonary TB, respectively. Most of the target genes of exclusively differentially expressed miRNAs were enriched in pathways in cancer, MAPK signalling pathway and Ras signalling pathway. Interpretation & conclusions The present study demonstrates a distinct expression profile of miRNAs in serum exosomes of the study participants and identified crucial miRNAs which may have a significant impact on the biomarker analysis and pathogenesis of TB in Indian patients.

To identify the differences in inflammatory response between critically ill patients responding to combined bacterial-fungal sepsis and those with isolated fungal sepsis. A retrospective case-control study compared ICU patients who were exposed (n=24) and unexposed (n=20) to candidemia. Two exposure modes were analyzed: isolated candidemia (C; n=12) versus candidemia with bacterial co-infection (BC; n=12). Targeted proximity extension assay (PEA) was used to examine differences in serum inflammatory proteome between groups. Differential inflammatory proteins served as input for a logistic regression model to validate their effectiveness in discrimination. Two major clusters-candidemia cases and controls-were identified based on differential protein expression analysis. In five-fold cross-validation, LAP-TGF beta-1 was identified as the main driver, effectively distinguishing isolated candidemia [AUC 0.95; 95% CI 0.853-1.000]. TRANCE and IL-17C showed potential as a diagnostic signature indicating bacterial co-infection in the context of candidemia. The three-protein logistic regression panel (LAP-TGF beta-1, TRANCE and IL-17C) differentiated cases with isolated candidemia from those with candidemia and bacterial co-infection [AUC 0.82; 95% CI 0.629-0.968]. A three-protein inflammatory signature distinguished isolated fungal sepsis from combined bacterial-fungal sepsis. This study is the first to explore the inflammatory response to differentiate isolated candidemia from candidemia with bacterial co-infection.

In canine leishmaniosis caused by the protozoan Leishmania infantum , little is known about how co-infections with or co-seropositivities for other pathogens can influence aggravation of this disease. Therefore, the objectives of this study were to evaluate the frequency of co-infections with or co-seropositivities for certain pathogens in dogs seropositive for L . infantum and their relationship with clinical signs, histological changes and L . infantum load. Sixty-six L . infantum -seropositive dogs were submitted to clinical examination, collection of blood and bone marrow, culling, and necropsy. Antibodies against Anaplasma spp., Borrelia burgdorferi sensu lato, Ehrlichia spp. and Toxoplasma gondii and Dirofilaria immitis antigens were investigated in serum. Samples from different tissues were submitted to histopathology and immunohistochemistry for the detection of Leishmania spp. and T . gondii . Quantitative real-time PCR was used to assess the L . infantum load in spleen samples. For detection of Coxiella burnetii , conventional PCR and nested PCR were performed using bone marrow samples. All 66 dogs tested positive for L . infantum by qPCR and/or culture. Fifty dogs (76%) were co-seropositive for at least one pathogen: T . gondii (59%), Ehrlichia spp., (41%), and Anaplasma spp. (18%). Clinical signs were observed in 15 (94%) dogs monoinfected with L . infantum and in 45 (90%) dogs co-seropositive for certain pathogens. The L . infantum load in spleen and skin did not differ significantly between monoinfected and co-seropositive dogs. The number of inflammatory cells was higher in the spleen, lung and mammary gland of co-seropositive dogs and in the mitral valve of monoinfected dogs. These results suggest that dogs infected with L . infantum and co-seropositive for certain pathogens are common in the region studied. However, co-seropositivities for certain pathogens did not aggravate clinical signs or L . infantum load, although they were associated with a more intense inflammatory reaction in some organs.