Concurrent cavitary pulmonary tuberculosis and COVID-19 pneumonia with in vitro immune cell anergy.

Tuberculosis (TB) is top infectious disease killer caused by a single organism responsible for 1.5 million deaths in 2018. Both COVID-19 and the pandemic response are risking to affect control measures for TB and continuity of essential services for people affected by this infection in western countries and even more in developing countries. Knowledge about concomitant pulmonary TB and COVID-19 is extremely limited. The double burden of these two diseases can have devastating effects. Here, we describe from both the clinical and the immunological point of view a case of a patient with in vitro immune cell anergy affected by bilateral cavitary pulmonary TB and subsequent COVID-19-associated pneumonia with a worst outcome. COVID-19 can be a precipitating factor in TB respiratory failure and, during ongoing SARS-COV-2 pandemic, clinicians must be aware of this possible co-infection in differential diagnosis of patients with active TB and new or worsening chest imaging.

Impact of High-Dose Multi-Strain Probiotic Supplementation on Neurocognitive Performance and Central Nervous System Immune Activation of HIV-1 Infected Individuals.

BACKGROUND: Gut microbiota has metabolic activity which influences mucosal homeostasis, local and systemic immune responses, and other anatomical systems (i.e., brain). The effects of dysbiosis are still poorly studied in Human Immunodeficiency Virus-1 (HIV-1) positive subjects and insufficient data are available on the impairment of the gut-brain axis, despite neurocognitive disorders being commonly diagnosed in these patients. This study evaluated the impact of a probiotic supplementation strategy on intrathecal immune activation and cognitive performance in combined antiretroviral therapy (cART) treated HIV-1 infected subjects. METHODS: Thirty-five HIV-1 infected individuals were included in this study. At baseline (T0) a battery of tests was administered, to evaluate neurocognitive function and a lumbar puncture was performed to determine neopterin concentration in cerebrospinal fluid (CSF), as a marker of Central Nervous System (CNS) immune activation. Subsequently, a subgroup of participants underwent a 6-month course of multi-strain probiotics supplementation; this intervention group was evaluated, after probiotic treatment, with a second lumbar puncture and with repeated neurocognitive tests. RESULTS: At T0, all participants showed impaired results in at least one neurocognitive test and elevated neopterin concentrations in CSF. After supplementation with probiotics (T6), the interventional group presented a significant decrease in neopterin concentration and a significant improvement in several neurocognitive tests. In contrast, no significant modifications were observed in the neurocognitive performance of controls between T0 and T6. The CNS Penetration Effectiveness Score of antiretroviral therapy did not show an influence from any of the investigated variables. CONCLUSIONS: Multi-strain probiotic supplementation seems to exert a positive effect on neuroinflammation and neurocognitive impairment in HIV-1 infected subjects, but large trials are needed to support the concept that modulation of the gut microbiota can provide specific neurological benefits in these patients.

Modulation of Tryptophan/Serotonin Pathway by Probiotic Supplementation in Human Immunodeficiency Virus-Positive Patients: Preliminary Results of a New Study Approach.

BACKGROUND: To date, no data are available regarding the effects of probiotics on the pathway of tryptophan/serotonin metabolism among human immunodeficiency virus (HIV) 1-infected individuals. Because a condition of dysbiosis might be responsible for the altered use of tryptophan described in this population, the aim of this study was to investigate the link between probiotic supplementation and serotonin levels in combined antiretroviral therapy-treated patients and the subsistence of an interplay with inflammation. METHODS: We conducted a pilot study that included 8 HIV-positive subjects. We collected blood and fecal samples before and after 6 months of probiotic supplementation, to measure the level of serotonin in serum and tryptophan in stool, the expression of CD38 and HLA-DR on peripheral CD4+ T lymphocytes (as immune activation markers), the expression of indoleamine 2,3-dioxygenase 1 messenger RNA (mRNA) and IFN-γ mRNA (as markers of tryptophan metabolism and systemic inflammation). RESULTS: After probiotic supplementation, we observed a significant increase in concentration of serum serotonin (P = .008) and a decreased level of tryptophan in plasma. Moreover, a significant reduction in CD38 and HLA-DR expression on the surface of peripheral CD4+ T cells (P = .008) and a reduced expression of indoleamine 2,3-dioxygenase 1 mRNA on peripheral blood mononuclear cells (P = .04) were observed. CONCLUSIONS: Considering that this probiotic (Vivomixx® in EU; Visbiome® in USA) has an influence on tryptophan metabolism, larger studies on this topic are needed.

Probiotic supplementation promotes a reduction in T-cell activation, an increase in Th17 frequencies, and a recovery of intestinal epithelium integrity and mitochondrial morphology in ART-treated HIV-1-positive patients.

INTRODUCTION: HIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART-experienced HIV-1 patients was evaluated. METHODS: A sub-study of a longitudinal pilot study was performed in HIV-1 patients who received the probiotic supplement twice a day for 6 months (T6). T-cell activation and CD4+ and CD8+ T-cell subsets expressing IFNγ (Th1, Tc1) or IL-17A (Th17, Tc17) were stained by cytoflorimetric analysis. Histological and immunohistochemical analyses were performed on intestinal biopsies while enterocytes apoptosis index was determined by TUNEL assay. RESULTS: A reduction in the frequencies of CD4+ and CD8+ T-cell subsets, expressing CD38+ , HLA-DR+ , or both, and an increase in the percentage of Th17 cell subsets, especially those with central or effector memory phenotype, was recorded in the peripheral blood and in gut-associated lymphoid tissue (GALT) after probiotic intervention. Conversely, Tc1 and Tc17 levels remained substantially unchanged at T6, while Th1 cell subsets increase in the GALT. Probiotic supplementation was also associated to a recovery of the integrity of the gut epithelial barrier, a reduction of both intraepithelial lymphocytes density and enterocyte apoptosis and, an improvement of mitochondrial morphology sustained in part by a modulation of heat shock protein 60. CONCLUSIONS: These findings highlight the potential beneficial effects of probiotic supplementation for the reconstitution of physical and immunological integrity of the mucosal intestinal barrier in ART-treated HIV-1-positive patients.