Male reproductive health after 3 months from SARS-CoV-2 infection: a multicentric study.

PURPOSE: While SARS-CoV-2 infection appears not to be clinically evident in the testes, indirect inflammatory effects and fever may impair testicular function. To date, few long-term data of semen parameters impairment after recovery and comprehensive andrological evaluation of recovered patients has been published. The purpose of this study was to investigate whether SARS-CoV-2 infection affect male reproductive health. METHODS: Eighty patients were recruited three months after COVID-19 recovery. They performed physical examination, testicular ultrasound, semen analysis, sperm DNA integrity evaluation (TUNEL), anti-sperm antibodies (ASA) testing, sex hormone profile evaluation (Total testosterone, LH, FSH). In addition, all patients were administered International Index of Erectile Function questionnaire (IIEF-15). Sperm parameters were compared with two age-matched healthy pre-COVID-19 control groups of normozoospermic (CTR1) and primary infertile (CTR2) subjects. RESULTS: Median values of semen parameters from recovered SARS-CoV-2 subjects were within WHO 2010 fifth percentile. Mean percentage of sperm DNA fragmentation (%SDF) was 14.1 ± 7.0%. Gelatin Agglutination Test (GAT) was positive in 3.9% of blood serum samples, but no positive semen plasma sample was found. Only five subjects (6.2%) had total testosterone levels below the laboratory reference range. Mean bilateral testicular volume was 31.5 ± 9.6 ml. Erectile dysfunction was detected in 30% of subjects. CONCLUSION: Our data remark that COVID-19 does not seem to cause direct damage to the testicular function, while indirect damage appears to be transient. It is possible to counsel infertile couples to postpone the research of parenthood or ART procedures around three months after recovery from the infection.

Clinical and epidemiological features of HIV/AIDS infection among migrants at first access to healthcare services as compared to Italian patients in Italy: a retrospective multicentre study, 2000-2010.

PURPOSE: Migrants account for approximately 8.7% of the resident population in Italy. The immigration status deeply influences access to prevention and care, thus contributing to increase the burden of HIV/AIDS among such a fragile category. The aim of this study was to investigate socio-demographic and baseline clinical and immunological features of HIV-infected migrants, as compared to Italians. METHODS: We retrospectively analysed data for all the 1,611 HIV-infected migrant patients and a random sample of 4,230 HIV-infected Italian patients aged 18 or older who first accessed nine Italian clinical centres in 2000-2010 and were followed up at least 1 year. Differences in baseline characteristics between migrants and Italians were evaluated in univariate analysis, while factors associated with late presentation were evaluated in multivariate analysis using logistic regression models. RESULTS: The baseline profile differs between the HIV-infected migrant and Italian patients, substantially reflecting what reported by current statistics in terms of gender, age, risk category as well as clinical features. Late presenters were more frequent among migrants as compared to Italians (53.0 vs 45.8%; adjusted odds ratio [(AOR) = 1.55, 95% confidence interval (CI) 1.34-1.78]. Other factors associated with late presentation included increasing age, as well as undocumented legal status among foreign-born subjects (AOR = 1.41, 95% CI 0.97-2.04), though of borderline significance. CONCLUSIONS: Late presentation still represents a relevant problem despite the advances in the management of HIV infection. More efforts are needed to allow early diagnosis and access to care among the most vulnerable, such as undocumented foreign-born subjects in a country where migration flows are on the rise.

Interferon-γ release assay for tuberculosis in patients with psoriasis treated with tumour necrosis factor antagonists: in vivo and in vitro analysis.

BACKGROUND: Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to starting on tumour necrosis factor (TNF) blockers. OBJECTIVES: To investigate the longitudinal changes of interferon (IFN)-γ response to Mycobacterium tuberculosis-specific antigens by serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing in patients with psoriasis during long-term anti-TNF therapy. The direct in vitro effect of adalimumab on IFN-γ secretion was also evaluated. METHODS: In total, 148 patients with psoriasis designated to start anti-TNF treatment were enrolled. We performed a tuberculin skin test at screening, and QFT-GIT at baseline and serially for 24 months after TNF antagonist onset. RESULTS: At screening, QFT-GIT was positive in 22.3% of the patients, negative in 73.6% and indeterminate in 4%. The IFN-γ response following isoniazid therapy declined and became QFT-GIT negative in 8% of 26 patients with LTBI; in 69% of subjects with LTBI the QFT-GIT remained persistently positive with a significant increase of IFN-γ levels during the follow-up, even if no cases of active tuberculosis were found. Variations of IFN-γ levels were observed also in 7% of 27 patients without LTBI who switched to positive QFT-GIT after 12 or 18 months of biologic therapy, suggesting a new occurrence or reactivation of LTBI. In vitro data showed that in the presence of adalimumab the IFN-γ levels were significantly reduced in a dose-dependent manner (P < 0.05). CONCLUSIONS: Fluctuations of IFN-γ release may occur in patients with psoriasis treated with TNF antagonists. The clinical use of repeated blood tests and the correct interpretation of individual IFN-γ changes could be useful in identifying possible cases of LTBI reactivation or newly acquired tuberculosis infection during long-term anti-TNF treatment.

Late onset invasive pneumococcal disease in a liver transplanted patient: beyond the Austrian syndrome.

Invasive disease caused by Streptococcus pneumoniae is a major cause of morbidity and mortality in high-risk individuals with severe comorbidities, including asplenia, chronic alcoholism, and altered immune status. The risk of invasive pneumococcal disease has been significantly higher in transplant patients compared with the general population. Here, we report an unusual case of a disseminated pneumococcal infection with meningitis, endocarditis, spondylodiscitis, and muscle abscess in an asplenic patient on chronic immunosuppressive therapy for liver transplantation performed 17 years before.

Study of methicillin-resistant Staphylococcus aureus (MRSA) carriage in a population of HIV-negative migrants and HIV-infected patients attending an outpatient clinic in Rome.

BACKGROUND: Migration and HIV infection are known risk factors for methicillin-resistant Staphylococcus aureus (MRSA) carriage and infection. The aim of the study was to analyze the prevalence of MRSA nasal colonization in a high risk population of HIV-negative migrants and HIV-infected subjects. Secondary aim was to investigate over time MRSA carriage prevalence in HIV-infected subjects. METHODS: During the study period (January-June 2008), nasal swabs were collected from 96 HIV-negative migrants and 63 HIV-infected patients. A group of 68 seropositive subjects was additionally screened for MRSA carriage in 2012. Subjects were evaluated for HIV status, previous antibiotic use or hospitalization, soft tissue and skin infections (SSI), nationality and work conditions. The swab specimens were plated and incubated for 24-h under static condition at 37 degrees and then identified as S. aureus by using standard methods. RESULTS: A total of 227 subjects, 131 HIV-infected adults (63 in 2008 and 68 in 2012) and 96 HIV-negative migrants, were analyzed. Overall, 71/227 (31.2%) were S. aureus carriers: 34 out of 131 (25.9%) among HIV infected subjects and 37 out of 96 (38.5%) among migrants. Two MRSA were detected in HIV-infected patients (2.8%). Between 2008 and 2012 there was an increase of MRSA carriage in HIV+ group (p=0.49). No statistically significant differences were found between S. aureus carriers and no-carriers in terms of CD4+ cell count, TMP/SMX prophylaxis, previous antibiotic use or hospitalization, nationality and duration of stay in Italy. Among HIV+ patients there was a higher prevalence of SSI in MSSA carriers compared with no carriers (25% vs 4%, p=0.028). In the migrants group, having a job based on a close human contact was significantly associated with S. aureus colonization (p=0.0038). CONCLUSIONS: Despite of the high prevalence of S. aureus isolation (31.2%), the present study showed the low rate of MRSA carriage in a high risk population. The main factor associated with S. aureus colonization was a close human contact rather than the HIV status and the condition of being migrant.

Epidemiology of Chlamydia trachomatis endocervical infection in a previously unscreened population in Rome, Italy, 2000 to 2009.

As reliable data on Chlamydia trachomatis infection in Italy are lacking and as there is no Italian screening policy, epidemiological analyses are needed to optimise effective strategies for surveillance of the infection in the country. We collected data from 6,969 sexually active women aged 15 to 55 years who underwent testing for endocervical C. trachomatis infection at the Cervico-Vaginal Pathology Unit in the Department of Gynaecology and Obstetrics of Sapienza University in Rome between 2000 and 2009. The mean prevalence of C. trachomatis endocervical infection during this period was 5.2%. Prevalence over time did not show a linear trend. Univariate analysis demonstrated a significant association of infection with multiple lifetime sexual partners, younger age (<40 years), never having been pregnant, smoking, use of oral contraceptives, and human papillomavirus and Trichomonas vaginalis infections. Multivariate stepwise logistic regression showed that T. vaginalis infection, age under 20 years and more than one lifetime sexual partner remained significantly associated with C. trachomatis infection in the final model. Prevalence of C. trachomatis in this study was high, even among women aged 25­39 years (5.1%): our data would suggest that a C. trachomatis screening policy in Italy is warranted, which could lead to a more extensive testing strategy.

Blood glucose and epicardial adipose tissue at the hospital admission as possible predictors for COVID-19 severity.

PURPOSE: To study the possible association of CT-derived quantitative epicardial adipose tissue (EAT) and glycemia at the admission, with severe outcomes in patients with COVID-19. METHODS: Two hundred and twenty-nine patients consecutively hospitalized for COVID-19 from March 1st to June 30th 2020 were studied. Non contrast chest CT scans, to confirm diagnosis of pneumonia, were performed. EAT volume (cm3) and attenuation (Hounsfield units) were measured using a CT post-processing software. The primary outcome was acute respiratory distress syndrome (ARDS) or in-hospital death. RESULTS: The primary outcome occurred in 56.8% patients. Fasting blood glucose was significantly higher in the group ARDS/death than in the group with better prognosis [114 (98-144) vs. 101 (91-118) mg/dl, p = 0.001]. EAT volume was higher in patients with vs without the primary outcome [103 (69.25; 129.75) vs. 78.95 (50.7; 100.25) cm3, p < 0.001] and it was positively correlated with glycemia, PCR, fibrinogen, P/F ratio. In the multivariable logistic regression analysis, age and EAT volume were independently associated with ARDS/death. Glycemia and EAT attenuation would appear to be factors involved in ARDS/death with a trend of statistical significance. CONCLUSIONS: Our findings suggest that both blood glucose and EAT, easily measurable and modifiable targets, could be important predisposing factors for severe Covid-19 complications.

In vitro effect of anti-human immunodeficiency virus CCR5 antagonist maraviroc on chemotactic activity of monocytes, macrophages and dendritic cells.

Compounds targeting the chemokine receptor CCR5 have recently been approved for treatment of human immunodeficiency virus (HIV) infection. Given the central role of CCR5 in inflammation and recruitment of antigen-presenting cells (APC), it is important to investigate the immunological consequences of pharmacological inhibition of CCR5. We evaluated the in vitro effect of different concentrations of CCR5 antagonist maraviroc (MVC) on cell migration of monocytes, macrophages (MO) and monocyte-derived dendritic cells (MDC) towards peptide formyl-methionyl-leucyl-phenylalanine (fMLP) and chemokines regulated upon activation normal T cell expressed and secreted (RANTES) and CCL4/macrophage inflammatory protein-1 (MIP-1ß) and CCL2/monocyte chemotactic protein-1 (MCP-1). Results of flow cytometric analysis showed that monocytes treated in vitro with MVC exhibited a significant dose-dependent reduction of chemotaxis towards MIP-1ß and MCP-1. fMLP-induced chemotactic activity decreased only at higher concentration (1 µM and 10 µM of MVC). In addition, all concentrations of MVC (0·1, 1 and 10 µM) induced in vitro a significant inhibition of chemotaxis of MO and MDC in response to all tested chemoattractants. No change in phenotype (CD1a and CD14) and CCR1, CCR4, CCR5 and formyl peptide receptor (FPR) expression was seen after in vitro treatment with MVC. These findings suggest that CCR5 antagonist MVC may have the in vitro ability of inhibiting the migration of innate immune cells by mechanism which could be independent from the pure anti-HIV effect. The drug might have a potential role in the down-regulation of HIV-associated chronic inflammation by blocking the recirculation and trafficking of MO and MDC.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide or dual therapy-based regimens in HIV-infected individuals with viral load ≤50 copies/mL: does estimated glomerular filtration rate matter?

Our aim was to evaluate the association between recent eGFR values and risk of switching from TDF to TAF or dual therapy (DT) in real life. HIV-positive patients achieving HIV-RNA ≤50 copies/mL for the first time after starting a TDF-based regimen were included. Kaplan-Meier (KM) curves and Cox regression models were used to estimate the time from TDF to switch to TAF or DT. 1486 participants were included: median (IQR) age 36 (30-42) years; baseline CKD-EPI eGFR 99.92 (86.47-111.4) mL/min/1.73m2. We observed a consistently higher proportion of people with HIV-RNA ≤50 copies/mL who switched from TDF to TAF rather than to DT. By competing risk analysis, at 2 years from baseline, the probability of switching was 3.5% (95% CI 2.6-4.7%) to DT and 46.7% (42.8-48.5%) to TAF. A significantly higher probability of switching to TAF was found for patients receiving INSTI at baseline versus NNRTIs and PI/b [KM, 65.6% (61.7-69.4%) vs. 4.0% (1.8-6.1%) and 59.9% (52.7-67.2%), respectively; P < 0.0001]. eGFR <60 mL/min/1.73m2 both as time-fixed covariate at baseline or as current value was associated with a higher risk of switching to DT [aHR 6.68 (2.69-16.60) and 8.18 (3.54-18.90); P < 0.001] but not to TAF-based cART [aHR 0.94 (0.39-2.31), P = 0.897; and 1.19 (0.60-2.38), P = 0.617]. Counter to our original hypothesis, current eGFR is used by clinicians to guide switches to DT but does not appear to be a key determinant for switching to TAF.

Rapid decline of fasting glucose in HCV diabetic patients treated with direct-acting antiviral agents.

Association between hepatitis C virus (HCV) infection and diabetes has been widely postulated. Little is known about the effect of direct-acting antiviral agents (DAAs) on glycaemic control. The aim of our study was to evaluate the glycaemic control modifications in a case series of HCV-positive diabetic patients receiving DAAs. We retrospectively evaluated 149 HCV-positive patients in two different institutions affiliated with Sapienza University: Policlinico Umberto I of Rome and Ospedale Santa Maria Goretti of Latina. We were able to identify 29 patients with type 2 diabetes mellitus (19% of total population) who were receiving different interferon-free regimens. During-treatment fasting glucose (FG) values were available for 21 patients, and analysis revealed a statistically significant reduction (p 0.007); reduction mean value was -52.86 mg/dL. A glycated haemoglobin (A1C) value during treatment (at weeks 4, 8 and/or 12) was available for ten patients, and the analysis revealed a statistically significant reduction (p 0.021) with a reduction mean value of -1.95%. Six patients (23%) needed to reduce hypoglycaemic drugs, eight of ten patients showed reduction of A1C and 14 (67%) of 21 patients showed reduced FG during treatment. FG and A1C reductions values were independent from which DAA was present in the regimen, HCV genotype, body mass index and HIV status. In order to avoid hypoglycaemic events, diabetic patients receiving DAAs should be closely monitored for reduction of hypoglycaemic drugs. Furthermore, in our opinion, diabetes could be considered as an element to prioritize treatment in those patients with no apparent liver disease.

Spontaneous and anti-Fas-induced apoptosis in lymphocytes from HIV-infected patients undergoing highly active anti-retroviral therapy.

OBJECTIVE: The aim of this study was to investigate susceptibility to spontaneous or anti-Fas-induced apoptosis in peripheral blood mononuclear cells (PBMC) from HIV-positive patients before and during highly active anti-retroviral therapy (HAART). DESIGN: A longitudinal study was performed on 12 evaluable patients on HAART. This cohort was analysed prior to and at week 2, 4, 8, 16 and 24 after beginning HAART. Variations in CD4 and CD8 cells, viral load, susceptibility to spontaneous or anti-Fas-induced apoptosis in the presence of IL-2, IL-4 or IL-12 were studied. Expression of Fas and Bcl-2 were also assessed. METHODS: Levels of HIV RNA were determined by a quantitative reverse transcription-PCR assay. Apoptosis was evaluated by staining isolated nuclei with propidium iodide followed by multiparameter flow cytometry analysis. RESULTS: Spontaneous apoptosis of PBMC was promptly inhibited after the start of treatment. Similarly, anti-Fas-induced apoptosis diminished greatly during treatment. Expression of Fas decreased significantly, while that of Bcl-2 remained statistically unchanged during the first 24 weeks of therapy. Levels of apoptosis correlated inversely to CD4 cell counts and directly to viral load in a highly significant way. Expression of Fas was directly correlated to apoptosis. Interleukin (IL)-2, but not IL-4 or IL-12, protected PBMC of HIV-positive individuals from spontaneous or anti-Fas-induced apoptosis before and during HAART. CONCLUSION: These results suggest that regulation of apoptosis and of Fas expression are involved in immunoreconstitution during HAART.

Improvement in neutrophil and monocyte function during highly active antiretroviral treatment of HIV-1-infected patients.

OBJECTIVE: To investigate the effect of highly active antiretroviral treatment (HAART) on neutrophil and monocyte function in patients with moderately advanced HIV-1 infection. DESIGN: Eighteen HIV-1-infected patients with CD4 T cell counts below 350/microl, no concomitant active infection, and no previous use of protease inhibitors were treated with indinavir or ritonavir and two reverse-transcriptase inhibitors and were followed up for 9 months. Ten age- and sex-matched healthy subjects were included as controls. METHODS: The functional activity of neutrophils and monocytes was measured by assessing chemotaxis towards a bacterial peptide, killing activity against Candida albicans, and oxidative burst as measured by chemiluminescence production. RESULTS: Neutrophils and monocytes from the treatment group exhibited a significantly diminished baseline chemotactic and fungicidal activity compared with healthy controls (P < 0.001). After starting HAART, there was a significant improvement in chemotaxis and fungicidal activity of phagocytic cells (P < 0.001). Values of chemotaxis reached normal ranges in 13 out of 18 patients (72%) for neutrophils and eight out of 18 (44%) for monocytes, whereas phagocyte killing was rarely restored to normal values (3/18 cases for monocytes and 0/18 for neutrophils). The administration of HAART was also associated with significantly increased phagocyte chemiluminescence production in response to phorbol-12-myristate 13-acetate or opsonized C. albicans (P < 0.01). CONCLUSION: The functional improvement of two critical components of innate antimicrobial immunity, such as neutrophils and monocytes, may contribute to the improved cell-mediated immune responses against opportunistic infections in HAART-treated patients.

Search for an antibody profile of Rhodococcus equi infection in AIDS patients despite the diversity of isolates and patient immune dysfunction.

Diversity of virulence-associated antigens of Rhodococcus equi was detected among thirteen strains isolated from AIDS patients on two continents. One out of four Brazilian isolates presented the virulence-associated antigen of 15- to 17-kDa, and the other three isolates had the 20-kDa virulence-associated antigen. In contrast, only three out of nine Italian isolates were positive for virulence-associated antigens - two for the 15- to 17-kDa antigen and one for the 20-kDa antigen. In four other Italian strains, one or more other low-molecular-weight antigens were identified. Because of R. equi variability and host immune dysfunction, no characteristic antibody profile was detected among patients, although the presence of specific antibodies in serum samples suggested prognostic value: good patient outcome and recovery from pneumonia were correlated with R. equi antibody detection, whereas the lack or disappearance of specific antibodies, mainly those to low-molecular-weight antigens, was correlated with disease progression and patient death. These results confirmed the nonobligatory presence of the well-known virulence-associated antigens for the pathogenicity of R. equi in humans, and also the diversity of R. equi strains isolated from AIDS patients, which may be related to the geographic origin of the isolates or may be a consequence of the route of R. equi transmission in different countries. Some mechanisms underlying the results obtained are discussed, suggesting immune complex formation during the progress of the disease.

Circulating levels of interleukin-7 in antiretroviral-naïve and highly active antiretroviral therapy-treated HIV-infected patients.

UNLABELLED: Interleukin (IL)-7 is a critical cytokine regulating T-lymphocyte development, regeneration, and function. PURPOSE: This study analyzes the endogenous IL-7 production in HIV-infected patients receiving highly active antiretroviral treatment (HAART). METHOD: Plasma levels of IL-7 were measured by enzyme-linked immunosorbent assay (ELISA) in 11 patients with untreated advanced HIV disease, in 8 patients who successfully responded to HAART, and in 9 individuals with virological and immunological treatment failure. RESULTS: We found that in the patients with advanced HIV disease and no treatment IL-7 concentrations were elevated and were inversely related to both CD4 + and CD8 + T-cell counts. When IL-7 was assessed in treated patients, this cytokine was below the detection limit of the assay in all participants who responded to HAART. On the contrary, patients with evidence of HAART failure had increased concentrations of IL-7 that were comparable to those found in the untreated group with progressive disease. CONCLUSION: These data suggest that IL-7 may play a role in the immune reconstitution of T-cells during HIV infection, especially in the context of potent antiretroviral treatments.

Rhodococcus equi infection of monocytes/macrophages from human immunodeficiency virus (HIV)-infected patients and healthy individuals: evaluation of intracellular killing and nitric oxide production.

Monocytes/macrophages from human immunodeficiency virus (HIV)-infected patients had a defect in their ability to kill Rhodococeus equi in vitro, as compared with healthy HIV-seronegative individuals. Virulent and avirulent R. equi strains isolated from humans and horses showed no significant intracellular replicative differences within both HIV-positive and -negative monocytes/macrophages. Infection with R. equi induced the production of nitric oxide (NO) by monocytes/macrophages from healthy individuals, but not by cells from HIV-positive patients. The NO formation was significantly inhibited by L-NG-monomethyl arginine and arginase. However. neither competitive inhibition of NO synthesis from L-arginine with L-NMMA nor depletion of arginine with arginase altered the killing activity of human monocytes/macrophages against R. equi, thus suggesting that L-arginine:NO pathway is not required for the intracellular antirhodococcal mechanisms of human monocytes/macrophages.

Central nervous system involvement as a relapse of disseminated histoplasmosis in an Italian AIDS patient.

A case of an Italian AIDS patient who developed both meningitis and cerebral mass lesion as a final relapse of disseminated histoplasmosis is reported. Central nervous system (CNS) involvement occurred while the patient was receiving both amphotericin B and itraconazole as maintenance therapy, thus indicating the difficulty of eradicating histoplasmosis in patients with AIDS.

Long-term remission of human immunodeficiency virus-associated visceral leishmaniasis after initiation of potent combination antiretroviral treatment: report of two cases.

We describe two cases of human immunodeficiency virus-infected patients with visceral leishmaniasis in whom no clinical and parasitological disease relapses were observed after liposomal amphotericin B therapy combined with potent antiretroviral treatment.

In vitro production of tumor necrosis factor-alpha, interleukin-6 and interleukin-8 from normal human peripheral blood mononuclear cells stimulated by Rhodococcus equi.

The capability of heat-killed Rhodococcus equi organisms to induce in vitro release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 from normal human mononuclear cells as well as the secretion kinetics of these inflammatory cytokines over a 48 h period were evaluated. Results show that normal human mononuclear cells are efficiently triggered to secrete TNF-alpha, IL-6 and IL-8 following R. equi stimulation according to a different kinetics. In particular, release of IL-B was already maximally expressed after 2 h of stimulation, while TNF-alpha amounts progressively increased in a time-dependent fashion. Finally, IL-6 secretion reached peak levels as soon as 18 h of incubation. Taken together, these data point out that monocyte-derived cytokines may play an important role in the immunological control of R. equi infection in immunocompetent people.