Role of HBcAb Positivity in Increase of HIV-RNA Detectability after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Months 48 Results of a Multicenter Italian Cohort

: The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of HIV viremia in patients living with HIV (PLWH) who switch to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC-based). A retrospective multicentre observational study was conducted on 160 PLWH switching to the 2DR-3TC-based regimen: 51 HBcAb-positive and 109 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly lower percentage of subjects with HIV viral suppression with target not detected (TND) at all time points after switching (24th month: 64.7% vs. 87.8%, p < 0.0001; 36th month 62.7% vs. 86.8%, p = 0.011; 48th month 57.2% vs. 86.1%, p = 0.021 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that the presence of HBcAb positivity (OR 7.46 [95% CI 2.35-14.77], p = 0.004) could favour the emergence of HIV viral rebound by nearly 54% during the entire study follow-up after switching to 2DR-3TC

Validation of the T-Lymphocyte Subset Index (TLSI) as a Score to Predict Mortality in Unvaccinated Hospitalized COVID-19 Patients

Lymphopenia has been consistently reported as associated with severe coronavirus disease 2019 (COVID-19). Several studies have described a profound decline in all T-cell subtypes in hospitalized patients with severe and critical COVID-19. The aim of this study was to assess the role of T-lymphocyte subset absolute counts measured at ward admission in predicting 30-day mortality in COVID-19 hospitalized patients, validating a new prognostic score, the T-Lymphocyte Subset Index (TLSI, range 0–2), based on the number of T-cell subset (CD4+ and CD8+) absolute counts that are below prespecified cutoffs. These cutoff values derive from a previously published work of our research group at Policlinico Tor Vergata, Rome, Italy: CD3+CD4+ < 369 cells/µL, CD3+CD8+ < 194 cells/µL. In the present single-center retrospective study, T-cell subsets were assessed on admission to the infectious diseases ward. Statistical analysis was performed using JASP (Version 0.16.2. JASP Team, 2022, The Amsterdam, The Netherlands) and Prism8 (version 8.2.1. GraphPad Software, San Diego, CA, USA). Clinical and laboratory parameters of 296 adult patients hospitalized because of COVID-19 were analyzed. The overall mortality rate was 22.3% (66/296). Survivors (S) had a statistically significant lower TLSI score compared to non-survivors (NS) (p < 0.001). Patients with increasing TLSI scores had proportionally higher rates of 30-day mortality (p < 0.0001). In the multivariable logistic analysis, the TLSI was an independent predictor of in-hospital 30-day mortality (OR: 1.893, p = 0.003). Survival analysis showed that patients with a TLSI > 0 had an increased risk of death compared to patients with a TLSI = 0 (hazard ratio: 2.83, p < 0.0001). The TLSI was confirmed as an early and independent predictor of COVID-19 in-hospital 30-day mortalit

Multiple acyl-COA dehydrogenase deficiency in elderly carriers

Multiple acyl-CoA dehydrogenase deficiency, or glutaric aciduria type II, is an autosomal recessive disorder of fatty acid oxidation due to defects in electron transfer flavoprotein (ETF) encoded by ETFA and ETFB, or in electron transfer flavoprotein dehydrogenase (ETFDH) encoded by the ETFDH gene. The disease may present as a severe neonatal onset form and a mild late-onset form which is heterogeneous for the age at onset and clinical presentation. We describe two patients in their seventies, referred for a nonspecific myopathy, which resulted to manifest carriers of ETFDH gene mutation. Treatment with riboflavin and L-carnitine improved the clinical picture and the biochemical profile. This condition should be included in the differential diagnosis of myopathies even at an old age

Remdesivir Influence on SARS-CoV-2 RNA Viral Load Kinetics in Nasopharyngeal Swab Specimens of COVID-19 Hospitalized Patients: A Real-Life Experience

There are still conflicting data on the virological effects of the SARS-CoV-2 direct antivirals used in clinical practice, in spite of the documented clinical efficacy. The aim of this monocentric retrospective study was to compare virologic and laboratory data of patients admitted due to SARS-CoV-2 infection from March to December 2020 treated with either remdesivir (R), a protease inhibitor (lopinavir or darunavir/ritonavir (PI)) or no direct antiviral drugs (NT). Viral load variation was indirectly assessed through PCR cycle threshold (Ct) values on the nasopharyngeal swab, analyzing the results from swabs obtained at ward admission and 7 (±2) days later. Overall, 253 patients were included: patients in the R group were significantly older, more frequently males with a significantly higher percentage of severe COVID-19, requiring more often intensive care admission, compared to the other groups. Ct variation over time did not differ amongst the three treatment groups and did not seem to be influenced by corticosteroid use, even after normalization of the treatment groups for disease severity. Non-survivors had lower Ct on admission and showed a significantly slower viral clearance compared to survivors. CD4 T-lymphocytes absolute count assessed at ward admission correlated with a reduced Ct variation over time. In conclusion, viral clearance appears to be slower in COVID-19 non-survivors, while it seems not to be influenced by the antiviral treatment received

High CD169 Monocyte/Lymphocyte Ratio Reflects Immunophenotype Disruption and Oxygen Need in COVID-19 Patients

International audienceBackground: Sialoadhesin (CD169) has been found to be overexpressed in the blood of COVID-19 patients and identified as a biomarker in early disease. We analyzed CD169 in the blood cells of COVID-19 patients to assess its role as a predictive marker of disease progression and clinical outcomes. Methods: The ratio of the median fluorescence intensity of CD169 between monocytes and lymphocytes (CD169 RMFI) was analyzed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HDs) and correlated with immunophenotyping, inflammatory markers, cytokine mRNA expression, pulmonary involvement, and disease progression. Results: CD169 RMFI was high in COV but not in HDs, and it correlated with CD8 T-cell senescence and exhaustion markers, as well as with B-cell maturation and differentiation in COV. CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients who were untreated at sampling, and was associated with the respiratory outcome throughout hospitalization. Finally, we also report the first evidence of the specific ability of the spike protein of SARS-CoV-2 to trigger CD169 RMFI in a dose-dependent manner in parallel with IL-6 and IL-10 gene transcription in HD PBMCs stimulated in vitro. Conclusion: CD169 is induced by the spike protein and should be considered as an early biomarker for evaluating immune dysfunction and respiratory outcomes in COVID-19 patients

Baseline T-lymphocyte subset absolute counts can predict both outcome and severity in SARS-CoV-2 infected patients: a single center study

Abstract The aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p < 0.001). Multivariable logistic regression analysis showed that absolute counts of CD3+ T-lymphocytes < 524 cells/µl, CD3+ CD4+ < 369 cells/µl, and the number of T-lymphocyte subsets below the cutoff (T-lymphocyte subset index [TLSI]) were independent predictors of in-hospital mortality. Baseline T-lymphocyte subset counts and TLSI were also predictive of disease severity (CD3+  < 733 cells/µl; CD3+ CD4+ < 426 cells/µl; CD3+ CD8+ < 262 cells/µl; CD3+ DP < 4.5 cells/µl; CD3+ DN < 18.5 cells/µl). The evaluation of peripheral T-lymphocyte absolute counts in the early stages of COVID-19 might represent a useful tool for identifying patients at increased risk of unfavorable outcomes

Role of HBcAb Positivity in Increase of HIV-RNA Detectability after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Months 48 Results of a Multicenter Italian Cohort

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of HIV viremia in patients living with HIV (PLWH) who switch to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC-based). A retrospective multicentre observational study was conducted on 160 PLWH switching to the 2DR-3TC-based regimen: 51 HBcAb-positive and 109 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly lower percentage of subjects with HIV viral suppression with target not detected (TND) at all time points after switching (24th month: 64.7% vs. 87.8%, p p = 0.011; 48th month 57.2% vs. 86.1%, p = 0.021 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that the presence of HBcAb positivity (OR 7.46 [95% CI 2.35–14.77], p = 0.004) could favour the emergence of HIV viral rebound by nearly 54% during the entire study follow-up after switching to 2DR-3TC

Persistence of circulating CD169+monocytes and HLA-DR downregulation underline the immune response impairment in PASC individuals: the potential contribution of different COVID-19 pandemic waves

The use of CD169 as a marker of viral infection has been widely discussed in the context of COVID-19, and in particular, its crucial role in the early detection of SARS-CoV-2 infection and its association with the severity and clinical outcome of COVID-19 were demonstrated. COVID-19 patients show relevant systemic alteration and immunological dysfunction that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). It is critical to implement the characterization of the disease, focusing also on the possible impact of the different COVID-19 waves and the consequent effects found after infection. On this basis, we evaluated by flow cytometry the expression of CD169 and HLA-DR on monocytes from COVID-19 patients and PASC individuals to better elucidate their involvement in immunological dysfunction, also evaluating the possible impact of different pandemic waves. The results confirm CD169 RMFI is a good marker of viral infection. Moreover, COVID-19 patients and PASC individuals showed high percentage of CD169+ monocytes, but low percentage of HLA-DR+ monocytes and the alteration of systemic inflammatory indices. We have also observed alterations of CD169 and HLA-DR expression and indices of inflammation upon different COVID-19 waves. The persistence of specific myeloid subpopulations suggests a role of CD169+ monocytes and HLA-DR in COVID-19 disease and chronic post-infection inflammation, opening new opportunities to evaluate the impact of specific pandemic waves on the immune response impairment and systemic alterations with the perspective to provide new tools to monitoring new variants and diseases associated to emerging respiratory viruses