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Summary: Background: Severe and prolonged mpox courses have been described during the 2022–2023 outbreak. Identifying predictors of severe evolution is crucial for improving management and therapeutic strategies. We explored the predictors of mpox severity and tested the association between mpox severity and viral load in biological fluids. We also analysed the predictors of disease duration and kinetics of inflammatory markers and described the viral presence and duration of shedding in biological fluids. Methods: This multicentre historical cohort study included adults diagnosed with laboratory-confirmed mpox diagnosis between May 2022 and September 2023 at 15 Italian centres. Patients were followed up from the day of diagnosis until clinical recovery. Biological fluids (blood, urine, saliva, and oropharyngeal and rectal swabs) were collected from each subgroup during the course of the disease and after healing. The primary outcomes were disease severity (presence of mucosal involvement, extended rash, or need for hospitalisation) and its association with the cycle threshold value (Ct-value, surrogate of viral load) in biological fluids, using standard linear and linear mixed-effect logistic regression models. Among the secondary outcomes, predictors of disease duration were assessed using a linear regression model. Findings: A total of 541 patients were enrolled, including four (0.74%) women, with a median age of 38 years (IQR 33–44). Among the 235 people living with HIV (PLWH) (43.44%), 22 (4.07%) had a CD4 count lower than 350 cells/μL. Severe mpox was reported in 215 patients (39.74%). No patient died. Multivariable analysis showed that, severe mpox was more likely among Caucasians (OR 1.82; 95% CI 1.14–2.90, p = 0.012) and patients who had an onset of fever (1.95; 1.27–2.99, p = 0.002), lymphadenopathy (2.30; 1.52–3.48, p

Background: Prevention of latent tuberculosis infection (LTBI) in healthcare workers (HCWs) to ensure the “Right to Occupational Safety” is a special challenge globally, as HCWs have a higher risk of acquiring the infection in hospital settings because of frequent close exposure to patients suffering from tuberculosis (TB). Methods: Aretrospective study was performed with the aim of assessing the prevalence of LTBI related to demographical and occupational risk factors among HCWs employed in a large hospital in Italy. The study involved 1461 HCWs screened for LTBI by Mantoux tuberculin skin test (TST) and then confirmed with Interferon Gamma Release Assay (IGRA) test in case of positivity. Immunosuppressed and BGC-vaccinated workers were tested directly with IGRA. Results: LTBI was diagnosed in 4.1% of the HCWs and the prevalence resulted lower than other studies conducted in low TB incidence countries. The variables significantly linked with higher frequency of the infection were: age ≥40 years (OR = 3.14; 95% CI: 1.13–8.74; p < 0.05), length of service ≥15 years (OR = 4.11; 95% CI: 1.48–11.43; p < 0.05) and not being trained on TB prevention (OR = 3.46; 95% CI: 1.85–6.46; p < 0.05). Not trained HCWs presented a higher risk of LTBI also after adjustment for age and length of service, compared to trained HCWs. Conclusions: screening of HCWs for LTBI should be always considered in routinely occupational surveillance in order to early diagnose the infection and prevent its progression. Safety policies in hospital settings centered on workers’ training on TB prevention is crucial to minimize LTBI occurrence in HCWs.

Despite Parvovirus B19 (B19V) generally causing mild or asymptomatic infections, and only certain high-risk groups such as hematological or immunocompromised patients and pregnant women tending to develop complications, several factors challenge the assumption of a “benign” clinical course in immunocompetent adults and adolescents. A significant proportion of the population may harbor undiagnosed health conditions or genetic predispositions that could render them more susceptible to severe B19V complications. These could include mild hematological disorders, immune dysregulation not resulting in overt immunodeficiency, or underlying cardiac conditions. Concurrent infections with other pathogens, even seemingly minor ones, could synergistically increase the severity of B19V infection, leading to more pronounced clinical manifestations. While not definitively proven, the possibility of emerging B19V strains with increased virulence or altered tissue tropism cannot be entirely discounted. Additionally, the period of pandemic-related restrictions likely led to reduced B19V circulation, potentially resulting in a cohort of young adults with limited natural immunity, making them more vulnerable to infection. Potential clinical consequences include atypical and severe presentations, even in individuals without known risk factors. The traditional focus on B19V primarily as a pediatric concern might lead to underdiagnosis or delayed diagnosis in adults, potentially hindering timely intervention and management. A surge in B19V-related complications, even if individually mild, could collectively strain healthcare resources, particularly in settings with limited capacity or pre-existing pressures. Possible recommendations are to heighten clinical awareness with a high index of suspicion for B19V infection in adults and adolescents presenting with compatible symptoms, even in the absence of classic risk factors. Additionally, expanding testing criteria and enhancing public health surveillance efforts would be prudent.

In recent decades, increases in temperature and tropical rainfall have facilitated the spread of mosquito species into temperate zones. Mosquitoes are vectors for many viruses, including West Nile virus (WNV) and dengue virus (DENV), and pose a serious threat to public health. This review covers most of the current knowledge on the mosquito species associated with the transmission of WNV and DENV and their geographical distribution and discusses the main vertebrate hosts involved in the cycles of WNV or DENV. It also describes virological and pathogenic aspects of WNV or DENV infection, including emerging concepts linking WNV and DENV to the reproductive system. Furthermore, it provides an epidemiological analysis of the human cases of WNV and DENV reported in Europe, from 1 January 2018 to 31 December 2023, with a particular focus on Italy. The first autochthonous cases of DENV infection, with the most likely vector being Aedes albopictus, have been observed in several European countries in recent years, with a high incidence in Italy in 2023. The lack of treatments and effective vaccines is a serious challenge. Currently, the primary strategy to prevent the spread of WNV and DENV infections in humans remains to limit the spread of mosquitoes.

Summary: Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%–86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. Methods: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT50, starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann–Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test. Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41–55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of −2.01 log2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08–0.92), p = 0.037; OR 0.30 (0.10–0.88), p = 0.029 and OR 0.19 (0.05–0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups. Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection. Funding: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS “Advanced grant 5 × 1000, 2021” and by the Italian Ministry of Health “Ricerca Corrente Linea 2”.

Background: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. Methods: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. Results: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people’s satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. Conclusions: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history.

Abstract Introduction Considering the reported efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS‐CoV‐2 patients. Methods The mRNA levels of IFN‐I, IFN‐related genes and cytokines were evaluated using RT/real‐time quantitative PCR. Results Vaccinated patients showed increased rate of negative SARS‐CoV‐2 PCR tests on nasopharyngeal swab compared with unvaccinated ones after mAbs treatment (p = .002). Unvaccinated patients had lower IFN‐α/ω and higher IFN‐related genes (IFNAR1, IFNAR2, IRF9, ISG15, ISG56 and IFI27) and cytokines (IL‐6, IL‐10 and TGF‐β) mRNA levels compared to vaccinated individuals before mAbs (p

Human papillomaviruses (HPVs) commonly infect the anogenital mucosa; most infections are transient, but a fraction of those caused by high-risk (HR) types persist and may lead to anogenital cancer. The epidemiology of HPV genotypes in anal infections in groups at different risk for anal cancer has not been well described in Italy. This retrospective study reports the results of HPV DNA testing and complete genotyping performed on anal swabs from 691 female and male patients attending proctology clinics in Rome during 2012–2021; one-third had repeated testing. Cumulative HPV positivity in 1212 anal swabs was approximately 60%, was not age related, and showed an increasing trend over the study period. HPV rates differed significantly by sex and HIV status: HIV-negative women had the lowest (43.6%) and HIV-positive men the highest (83.5%) HPV prevalence. HIV-positive men had more oncogenic HPV genotypes detected, more multiple infections, and the highest frequency of persistent infections. Two-thirds of all infections were vaccine-preventable. This study found that anal HPV infection rates are still elevated and even increasing in groups at low and high risk of developing anal cancer. Prevention programs need to be improved to reduce rates of anal infection in young women and men.

Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4 Hz) and alpha (8–12 Hz) rhythms in treatment-Naïve HIV (Naïve HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder.The present EEG database regarded 128 Naïve HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals.Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naïve HIV than in the control group. Furthermore, those abnormalities were greater in the Naïve HIV subgroup with executive and visuospatial deficits than the Naïve HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75–0.88) in the discrimination between the Naïve HIV individuals with executive and visuospatial deficits vs. Naïve HIV individuals with normal cognition and control individuals.In quiet wakefulness, Naïve HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal “hub” oscillating at the alpha frequency in quiet wakefulness as a brain network disorder.

Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS-CoV-2 response upon infection. To further characterize age-related differences, we studied type I and III interferon (IFN) response in SARS-CoV-2 infected and non-infected individuals of different ages. Specifically, levels of expression of type I (IFN-α, -β, -ε and -ω), type III (IFN-λ1, -λ2 and -λ3) IFNs and of the IFN-stimulated genes, ISG15 and ISG56 were quantified in nasopharyngeal cells from diagnostic swabs. Basal transcription of type I/III IFN genes was highest among children and decreased with age. Among SARS-CoV-2-infected individuals, only IFN-ε and -ω levels were significantly higher in children and young adults whereas ISGs were overexpressed in infected adults. The occurrence of symptoms in children and the need for hospitalization in adults were associated to higher transcription of several IFN genes. Starting from a pre-activated transcription level, the expression of type I and III IFNs was not highly up-regulated in children upon SARS-CoV-2 infection; young adults activated IFNs’ transcription at intermediate levels whereas older adults were characterized by higher ISGs and lower IFN-ε and -ω relative expression levels. Overall, our findings contribute to recognize components of a protective IFN response as a function of age, in the context of SARS-CoV-2 infection.

Abstract Objectives Gender-specific studies remain a neglected area of biomedical research. Recent reports have emphasized that sex-related biological factors may affect disease progression during HIV-1 infection. The aim of this study was to investigate the influence of sex on the levels of immune activation in the gut and in peripheral blood of individuals with HIV treated with fully suppressive antiretroviral therapy (ART). Methods Thirty individuals with HIV undergoing long-term fully suppressive ART were enrolled in this study. Lamina propria lymphocytes (LPL) and peripheral blood mononuclear cells (PBMCs) were isolated from gut biopsies collected by pancolonoscopy and peripheral blood samples. The expression of markers of immune activation was evaluated by multi-parametric flow cytometry. This is a sub analysis of ClinicalTrials.gov Identifier: NCT02276326 Results We observed differences in the levels of immune activation in the gut and in PBMCs, with values higher in the gut compartment compared to PBMCs. In addition, we found that the mean value of the levels of immune activation was higher in the women than in the men. Finally, we measured the markers of immune activation by mean relative difference (MRD) and confirmed the higher value in the women. Conclusion A significant sex-related difference in the level of immune activation was observed in a population of individuals with HIV on long-term ART. A more complete characterization of these differences may support the introduction of sex-specific approaches in the clinical management of individuals with HIV.

Management of patients with concomitant acute lymphoblastic leukemia (ALL) and COVID-19 infection is challenging. We describe the clinical history of a 40-year-old male with relapsed B-common ALL who developed Sars-CoV2 prior to treatment initiation with inotuzumab. Since the patient was asymptomatic for COVID-19, the first dose of inotuzumab was administered, followed by remdesivir as prophylaxis. However, a worsening in respiratory findings led to a delay in administering the following doses of inotuzumab. Interestingly, even if the patient did not receive the full inotuzumab cycle, he achieved a complete hematologic remission: furthermore, he spontaneously developed anti-sars-COV2 antibodies. COVID-19 treatment also included convalescent plasma, leading to negativization of the viral load. The patient, after COVID-19 recovery, received a second full cycle of inotuzumab, underwent allogeneic transplantation, and is currently in complete hematologic and molecular remission, in good clinical conditions, five months from allograft. Keywords: acute lymphoblastic leukemia, COVID-19, inotuzumab, remdesevir, convalescent plasma

Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment and subsequent indefinite chronic oral antimicrobial suppression (COAS), can be the only reasonable choice. The aim of this study was to investigate the role of COAS and its follow-up in the management of these cases. We retrospectively analyzed a cohort of 16 patients with a follow-up of at least 6 months (mean age 75 yo, 9F, 7M, 11 PJI, 5 FRI). All microbiological isolates were tetracycline-susceptible staphylococci and for this reason a minocycline-based COAS was adopted after debridement and 3 months of antibiogram-guided antibiotic treatment. Patient monitoring was carried out on a clinical basis, with bimonthly execution of the inflammation indices and serial radiolabeled leukocyte scintigraphy (LS). The overall median time of COAS follow-up was 15 months (min 6–max 30). Moreover, 62.5% of patients were still taking COAS with no relapse after cure at the last evaluation available. Clinical failure with a relapse of the infection was observed in 37.5% of patients; interestingly, 50% of them had previously stopped COAS due to side effects of the antibiotic used. In the COAS follow-up, a combination of clinical, laboratory and LS evaluation seems to monitor the infection properly. COAS can be considered as an interesting approach in patients not suitable for standard treatments of PJI or FRI but it requires careful monitoring.

Background: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Methods: We recruited an observational retrospective real-life cohort, including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the previous treatment regimen (the BICTEL cohort). Longitudinal nonparametric analyses and linear models were built. Results: After 96 weeks of follow-up, 164 PLWH were included, with 106 older than 55. Both the intention-to-treat and the per-protocol analysis showed low rates of virologic failure, independent of the pre-switch anchor drug. At week 96, a significant increase in CD4+ T cell count and in CD4+/CD8+ ratio was observed, inversely correlated with baseline immune status. Fasting serum lipid profile, total body weight, BMI, and hepatic function were not affected by the switch, without new onset of metabolic syndrome or weight gain. Compared to baseline, we observed a renal function worsening which is worthy of further follow-up. Conclusion: BIC/FTC/TAF is an effective, safe, and well-tolerated switching strategy for PLWH, especially among those older than 55.

Long COVID refers to patients with symptoms as fatigue, “brain fog,” pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB–). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7% of participants reported fatigue while 29.3% were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB– one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways.

Background: SARS-CoV-2 related immunopathology may be the driving cause underlying severe COVID-19. Through an immunophenotyping analysis on paired bronchoalveolar lavage fluid (BALF) and blood samples collected from mechanically ventilated patients with COVID-19-associated Acute Respiratory Distress Syndrome (CARDS), this study aimed to evaluate the cellular immune responses in survivors and non-survivors of COVID-19. Methods: A total of 36 paired clinical samples of bronchoalveolar lavage fluid (BALF) mononuclear cells (BALF-MC) and peripheral blood mononuclear cells (PBMC) were collected from 18 SARS-CoV-2-infected subjects admitted to the intensive care unit (ICU) of the Policlinico Umberto I, Sapienza University Hospital in Rome (Italy) for severe interstitial pneumonia. The frequencies of monocytes (total, classical, intermediate and non-classical) and Natural Killer (NK) cell subsets (total, CD56bright and CD56dim), as well as CD4+ and CD8+ T cell subsets [naïve, central memory (TCM) and effector memory (TEM)], and those expressing CD38 and/or HLADR were evaluated by multiparametric flow cytometry. Results: Survivors with CARDS exhibited higher frequencies of classical monocytes in blood compared to non-survivors (p < 0.05), while no differences in the frequencies of the other monocytes, NK cell and T cell subsets were recorded between these two groups of patients (p > 0.05). The only exception was for peripheral naïve CD4+ T cells levels that were reduced in non-survivors (p = 0.04). An increase in the levels of CD56bright (p = 0.012) and a decrease in CD56dim (p = 0.002) NK cell frequencies was also observed in BALF-MC samples compared to PBMC in deceased COVID-19 patients. Total CD4+ and CD8+ T cell levels in the lung compartment were lower compared to blood (p = 0.002 and p < 0.01, respectively) among non-survivors. Moreover, CD38 and HLA-DR were differentially expressed by CD4+ and CD8+ T cell subsets in BALF-MC and in PBMC among SARS-CoV-2-infected patients who died from COVID-19 (p < 0.05). Conclusions: These results show that the immune cellular profile in blood and pulmonary compartments was similar in survivors and non-survivors of COVID-19. T lymphocyte levels were reduced, but resulted highly immune-activated in the lung compartment of patients who faced a fatal outcome.

Contradictory results have been reported regarding interferon (IFN) lambda (λ1–3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1–3 and IFNγ mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) (n = 32) and in cells of paired bronchoalveolar lavages (BALs) (n = 12). Lower IFNλ1–3 values (p < 0.001 for IFNλ1 and 3 and p = 0.013 for IFNλ2) in the PBMCs of severely ill patients were found compared to healthy donors (n = 15). Reduced levels of IFNγ were also detected in patients’ PBMCs (p < 0.01) and BALs (p = 0.041) compared to healthy donors. The presence of secondary bacterial infections was associated with decreased IFNλ amounts in PBMCs (p = 0.001, p = 0.015 and p = 0.003, respectively) but increased concentrations of IFNλ3 (p = 0.022) in BALs. Patients with alterations in C-reactive protein, lactate dehydrogenase and D-dimer levels had decreased IFNλ1 and 3 (p = 0.003 and p < 0.001) and increased IFNγ (p = 0.08) in PBMCs. Analyzing Toll-like receptors (TLRs) involved in IFN production, we found that TLR3 was highly expressed (p = 0.033) in patients with bacterial superinfections, while TLR7 and 8 (p = 0.029 and p = 0.049) were reduced in BALs of deceased patients. Overall, severe COVID-19 might be characterized by dysregulation in IFNγ, IFNλ and TLR3, 7 and 8 production.

Background: The incidence of candidemia in severe COVID-19 patients (0.8–14%) is two- to ten-fold higher than in non-COVID-19 patients. Methods: This retrospective analysis aimed to analyse the incidence of bloodstream infections (BSI) due to Candida in a cohort of COVID-19 patients supported with ECMO. Results: Among 138 intubated and ventilated patients hospitalized for ≥10 days in the intensive care unit of a teaching hospital, 45 (32.6%) patients received ECMO support, while 93 patients (67.4%) did not meet ECMO criteria and were considered the control group. In the ECMO group, 16 episodes of candidaemia were observed, while only 13 in patients of the control group (36.0% vs. 14.0%, p-value 0.004). It was confirmed at the survival analysis (SHR: 2.86, 95% CI: 1.39–5.88) and at the multivariable analyses (aSHR: 3.91, 95% CI: 1.73–8.86). A higher candida score seemed to increase the hazard for candidemia occurrence (aSHR: 3.04, 95% CI: 2.09–4.42), while vasopressor therapy was negatively associated with the outcome (aSHR: 0.15, 95% CI: 0.05–0.43). Conclusions: This study confirms that the incidence of candidemia was significantly higher in critically ill COVID-19 patients supported with VV-ECMO than in critically ill COVID patients who did not meet criteria for VV-ECMO.

Despite the “migrants and COVID-19” topic has been neglected since felt marginal concerning other aspects of the SARS-CoV-2 pandemic, it represents a relevant public health issue in the European countries. This report describes COVID-19 containment strategies adopted in a large Italian reception center hosting recently arrived asylum-seeker migrants. Risk assessment and prevention measures adopted were described. Geo-spatial epidemiological analysis of the outbreak was reported. Significant gaps in the knowledge of self-protection measures from contagious diseases and in the perception of the pandemic risk were observed in migrants; health promotion activities, targeted to remove cultural barriers and improve behaviors appropriate to individual protection, were able to fulfill this gap. In low-resource settings, especially in closed communities, the implementation of social distancing strategies, the systematic use of individual protection devices, and active syndromic surveillance are essential tools to limit the risk of outbreaks. In the event of an outbreak, it is relevant to rapidly activate containment procedures based on systematic screening, isolation, and quarantine, taking into consideration the limits of tracing contacts within a closed community. Not being able to trace certain contacts, the geo-spatial epidemiological analysis of cases distribution could be key in the management of the outbreak. Interestingly, positive cases identified in our facility were all clinically pauci-symptomatic or asymptomatic. Dedicated strategies are needed to minimize the chance of SARS-CoV-2 transmission in a limited space such as reception centers and a vulnerable population such as migrants.

Objectives: Transmitted drug resistance (TDR) and HIV-1 genetic diversity may affect treatment efficacy and clinical outcomes. Here we describe the circulating viral subtypes and estimate the prevalence of drug resistance among antiretroviral therapy (ART)-naïve patients attending Sapienza University Hospital (Rome, Italy) from 2006–2017. Methods: Genotypic resistance testing (GRT) was performed on 668 ART-naïve patients for integrase (n = 52), protease and reverse transcriptase (n = 668) sequences. Results: Twenty-one different HIV-1 subtypes and circulating recombinant forms (CRFs) were identified. Subtype B was the most common (67.1%), followed by CRF02_AG (8.4%), and subtypes C and F (both 6.0%). A significantly increase in the proportion of non-B strains (P < 0.001) and the rate of non-Italian patients was observed over time. The overall prevalence of TDR was 9.4% (NRTI, 4.2%; NNRTI, 5.8%; and PI, 1.0%) and was higher in subtype B strains. Transmitted INSTI mutations (Q148H and G140S) responsible for high-level resistance to raltegravir and elvitegravir and intermediate resistance to dolutegravir and bictegravir were found, for the first time, in two individuals. Minor or accessory INSTI mutations were detected in 17.3% of patients. No significant decrease in the prevalence of TDR was documented over time. Conclusion: The significant increase in non-B subtypes suggests that the molecular epidemiology of HIV-1 is changing. Detection of a major INSTI mutation in two ART-naïve patients highlights the importance of performing GRT before commencing treatment. This finding and the lack of a significant reduction in TDRs underline the importance of continuous surveillance of resistance mutations.

Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation. Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers. Methods: This was an observational, retrospective, and multicenter study. We investigated the effect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virological suppression, optimal immunological recovery (defined as CD4 count ≥ 500/µL, CD4 ≥ 30%, and CD4/CD8 ≥ 1), and first-line ART regimen discontinuation by Cox regression analysis. Results: There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log10copies/mL and the median CD4 count was 456 cells/µL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥ 1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associated with a shorter time to virological suppression. Early ART emerged as an independent predictor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percentage count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs. Conclusions: In a large cohort of well-characterized patients with AEHI, we confirmed the beneficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunological markers associated with virological control.

Abstract The proportion of new diagnoses of HIV infection in immigrants residing in Italy raised from 11% in 1992 to 29.7% in 2018. To investigate the HIV clades circulating in this community a retrospective study was performed in 557 HIV-infected immigrants living in 12 Italian cities. Immigrants originated from East-Europe and Central-Asia (11.7%), North Africa and Middle East (7.3%), South and South-East Asia (7.2%), Latin America and the Caribbean (14.4%), and sub-Saharan Africa (59.4%). More than 87% of immigrants were on antiretroviral therapy (ART), although 26.6% of them were viremic. A 22.0% of immigrants had hepatitis (HBV and/or HCV) and/or tuberculosis. HIV phylogenetic analysis on sequences from 192 immigrants showed the presence of clades B (23.4%), G (16.1%), C (10.4%), A1 (9.4%), F1 (5.2%), D (1.6%) and Circulating Recombinant Forms (CRFs) (33.9%). CRF02_AG represented 72.3% of the total CRFs. Clusters between immigrants and Italian natives were also present. Drug resistance mutations to NRTI, NNRTI, and PI drug classes occurred in 29.1% of ART-treated and in 12.9% of ART-naïve individuals. These data highlight the need for tailored public health interventions in immigrants to avoid spreading in Italy of HIV genetic forms and ART-resistant variants, as well as HIV co-morbidities.

Abstract Background During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms: a virulent neurotropic pathogenic form and a latent non-pathogenic form. The neurotropic forms contain a rearranged NCCR and are typically found in the cerebrospinal fluid, brain or blood of PML patients. Case presentation We sequenced and critically examined JCPyV NCCR from isolates detected in the cerebrospinal fluid of four newly diagnosed progressive multifocal leukoencephalopathy patients: two HIV-positive and two HIV-negative multiple sclerosis patients. More complex NCCR rearrangements were observed in the two HIV-positive patients compared to the HIV-negative multiple sclerosis patients with PML. Conclusions The comparison of HIV-positive and HIV-negative MS patients with PML, allowed us to evidence the presence of a common pattern of JCPyV NCCR rearrangement, characterized by the deletion of the D-block, which could be one of the initial rearrangements of JCPyV NCCR needed for the development of PML.

Abstract Background A wide debate is ongoing regarding the role of cutaneous dysbiosis in the pathogenesis and evolution of difficult-to-treat chronic wounds. Nowadays, probiotic treatment considered as an useful tool to counteract dysbiosis but the evidence in regard to their therapeutic use in the setting of difficult-to-treat cutaneous ulcers is still poor. Aim: clinical report An 83-year-old woman suffering a critical limb ischemia and an infected difficult-to-treat ulcerated cutaneous lesion of the right leg, was complementary treated with local application of a mixture of probiotic bacteria. Methods Microbiological and metabolomic analysis were conducted on wound swabs obtained before and after bacteriotherapy. Results During the treatment course, a progressive healing of the lesion was observed with microbiological resolution of the polymicrobial infection of the wound. Metabolomic analysis showed a significant difference in the local concentration of propionate, 2-hydroxyisovalerate, 2-oxoisocaproate, 2,3-butanediol, putrescine, thymine, and trimethylamine before and after bacteriotherapy. Conclusion The microbiological and metabolomic results seem to confirm the usefulness of complementary probiotic treatment in difficult-to-treat infected wounds. Further investigations are needed to confirm these preliminary findings.

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) have raised concerns as common, frequent etiologic agents of nosocomial infections, and patients admitted to intensive care units (ICUs) present the highest risk for colonization and infection. The incidence of colonization and infection in trauma patients remains poorly investigated. The aim of this study was to assess the risk factors for Carbapenem-resistant (CR)-GNB colonization and the clinical impact of colonization acquisition in patients with severe trauma admitted to the ICU in a CR-GNB hyperendemic country. This is a retrospective observational study; clinical and laboratory data were extracted from the nosocomial infection surveillance system database. Among 54 severe trauma patients enrolled in the study, 28 patients were colonized by CR-GNB; 7 (12.96%) patients were already colonized at ICU admission; and 21 (38.89%) patients developed a new colonization during their ICU stay. Risk factors for colonization were the length of stay in the ICU (not colonized, 14.81 days ± 9.1 vs. colonized, 38.19 days ± 27.9; p-value = 0.001) and days of mechanical ventilation (not colonized, 8.46 days ± 7.67 vs. colonized, 22.19 days ± 15.09; p-value < 0.001). There was a strong statistical association between previous colonization and subsequent development of infection (OR = 80.6, 95% CI 4.5–1458.6, p-value < 0.001). Factors associated with the risk of infection in colonized patients also included a higher Charlson comorbidity index, a longer length of stay in the ICU, a longer duration of mechanical ventilation, and a longer duration of treatment with carbapenem and vasopressors (not infected vs. infected: 0(0–4) vs. 1(0–3), p = 0.012; 24.82 ± 16.77 vs. 47 ± 28.51, p = 0.016; 13.54 ± 15.84 vs. 31.7 ± 16.22, p = 0.008; 1.09 ± 1.14 vs. 7.82 ± 9.15, p = 0.008). The adoption of MDR-GNB colonization prevention strategies in critically ill patients with severe trauma is required to improve the quality of care and reduce nosocomial infections, length of hospital stay and mortality.

Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March–July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability.

Introduction. Knowledge of local and regional antimicrobial resistance (AMR) is crucial in clinical decision-making, especially with critically ill patients. The aim of this study was to investigate the rate and pattern of infections in valvular heart disease patients admitted to the intensive care unit (ICU) at the Salam Centre for Cardiac Surgery in Khartoum, Sudan (run by EMERGENCY NGO). Methods. This is a retrospective, observational study from a single, large international referral centre (part of a Regional Programme), which enrolled patients admitted to the ICU between 1 January and 31 December 2019. Data collected for each patient included demographic data, operating theatre/ICU data and microbiological cultures. Results. Over the study period, 611 patients were enrolled (elective surgery n = 491, urgent surgery n = 34 and urgent medical care n = 86). The infection rate was 14.2% and turned out to be higher in medical than in surgical patients (25.6% vs. 12.4%; p = 0.002; OR = 2.43) and higher in those undergoing urgent surgery than those undergoing elective (29.4% vs. 11.2%; p = 0.004; OR = 3.3). Infection was related to (a) SOFA score (p < 0.001), (b) ICU length of stay (p < 0.001) and (c) days from ICU admission to OT (p = 0.003). A significant relationship between the type of admission (elective, urgent surgery or medical) and the presence of infections was found (p < 0.001). The mortality rate was higher among infected patients (infected vs. infection-free: 10.3% vs. 2.1%; p < 0.001; OR = 5.38; 95% CI: 2.16–13.4; p < 0.001). Conclusions. Hospital-acquired infections remain a relevant preventable cause of mortality in our particular population.

Background: Although useful in the time-race against COVID-19, CPAP cannot provide oxygen over the physiological limits imposed by severe pulmonary impairments. In previous studies, we reported that the administration of the SLAB51 probiotics reduced risk of developing respiratory failure in severe COVID-19 patients through the activation of oxygen sparing mechanisms providing additional oxygen to organs critical for survival. Methods: This “real life” study is a retrospective analysis of SARS-CoV-2 infected patients with hypoxaemic acute respiratory failure secondary to COVID-19 pneumonia undergoing CPAP treatment. A group of patients managed with ad interim routinely used therapy (RUT) were compared to a second group treated with RUT associated with SLAB51 oral bacteriotherapy (OB). Results: At baseline, patients receiving SLAB51 showed significantly lower blood oxygenation than controls. An opposite condition was observed after 3 days of treatment, despite the significantly reduced amount of oxygen received by patients taking SLAB51. At 7 days, a lower prevalence of COVID-19 patients needing CPAP in the group taking probiotics was observed. The administration of SLAB51 is a complementary approach for ameliorating oxygenation conditions at the systemic level. Conclusion: This study proves that probiotic administration results in an additional boost in alleviating hypoxic conditions, permitting to limit on the use of CPAP and its contraindications.

Background: Mounting evidence suggests SARS-CoV-2 may impact on host microbiota and gut inflammation, infecting intestinal epithelial cells. This possible link and its implications can be investigated by observing the effects of modulation of the microbial flora in patients with COVID-19. The aim of this study was to compare the rate of mortality, the need of ICU hospitalization and the length of hospitalization in patients with severe COVID-19 pneumonia who received the best available therapy (BAT) vs. patients treated with BAT and supplemented with oral bacteriotherapy.Methods: This retrospective, observational cohort study included 200 adults with severe COVID-19 pneumonia. All patients received therapeutic regimens including low molecular weight heparin plus one or more between hydroxychloroquine, azithromycin, antivirals, and Tocilizumab. Oral bacteriotherapy was used as complementary treatment.Results: Out of the 200 patients, 112 received BAT without oral bacteriotherapy, and 88 BAT with oral bacteriotherapy. Crude mortality was 22%. Eleven percent died in the group of patients treated with BAT plus oral bacteriotherapy vs. 30% subjects in the group of patients managed only with BAT (p < 0.001). By multivariate analysis, the age >65 years, CRP >41.8 mg/L, Platelets

Bacillus circulans is mainly considered an opportunistic pathogen in immunocompromised patients. However, many different infections have been described in the literature: bacteremia, abscesses, meningitis, endophthalmitis, and wound infections.We observed a spondylodiscitis caused by Bacillus circulans in an immunocompetent patient. To date, this is the first case reported in literature. Vertebral osteomyelitis represents for clinicians a challenging infection to manage and treat, because of its insidious and indolent course. The diagnosis is frequently difficult and can often be delayed for several months and initially be misdiagnosed and mismanaged. For this reason, the clinical case was described and all published cases of infection caused by Bacillus circulans were reviewed.

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.

Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19.Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation.Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy.Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.

The hyperinflammatory phase represents the main cause for the clinical worsening of acute respiratory distress syndrome (ARDS) in Coronavirus disease 2019 (COVID-19), leading to the hypothesis that steroid therapy could be a mainstream treatment in COVID-19 patients. This is an observational study including all consecutive patients admitted to two Italian University Hospitals for COVID-19 from March 2020 to December 2021. The aim of this study was to describe clinical characteristics and outcome parameters of hospitalized COVID-19 patients treated with dexamethasone 6 mg once daily (standard-dose group) or methylprednisolone 40 mg twice daily (high-dose group). The primary outcome was the impact of these different steroid treatments on 30-day mortality. During the study period, 990 patients were evaluated: 695 (70.2%) receiving standard dosage of dexamethasone and 295 (29.8%) receiving a high dose of methylprednisolone. Cox regression analysis showed that chronic obstructive pulmonary disease (HR 1.98, CI95% 1.34–9.81, p = 0.002), chronic kidney disease (HR 5.21, CI95% 1.48–22.23, p = 0.001), oncologic disease (HR 2.81, CI95% 1.45–19.8, p = 0.005) and high-flow nasal cannula, continuous positive airway pressure or non-invasive ventilation oxygen therapy (HR 61.1, CI95% 5.12–511.1, p < 0.001) were independently associated with 30-day mortality; conversely, high-dose steroid therapy was associated with survival (HR 0.42, CI95% 0.38–0.86, p = 0.002) at 30 days. Kaplan–Meier curves for 30-day survival displayed a statistically significant better survival rate in patients treated with high-dose steroid therapy (p = 0.018). The results of this study highlighted that the use of high-dose methylprednisolone, compared to dexamethasone 6 mg once daily, in hospitalized patients with COVID-19 may be associated with a significant reduction in mortality.

Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We analyzed the genotype frequencies of IFNL4 single nucleotide polymorphism (SNP) rs11322783 in patients with COVID-19 (n = 128), in comparison with a validated data set of European healthy controls (n = 14152). The IFNL4 SNP was also analyzed according to the haematological and clinical parameters of patients with COVID-19. The distributions of IFNL4 genotypes among SARS-CoV-2 positive patients [TT/TT 41.4% (n = 53), TT/ΔG 47.7% (n = 61) and ΔG/ΔG 10.9% (n = 14)] and healthy controls were comparable. Different levels of white blood cells (p = 0.036) and neutrophils (p = 0.042) were found in the IFNL4 different genotypes in patients with COVID-19; the ΔG/ΔG genotype was more represented in the groups with low white blood cells and neutrophils. There were no differences in major inflammation parameters (C-reactive protein, D-dimer, Albumin, and Lactate-dehydrogenase (LDH)] and survival rate according to the IFNL4 genotypes. In conclusion, although patients with COVID-19 did not exhibit a different distribution of the IFNL4 SNP, the ΔG/ΔG genotype was associated with a lower count of immune cell populations. These findings need to be confirmed in larger groups of patients with COVID-19 and the role of IFNL4 SNP needs to be also investigated in other respiratory viral infections.

Objective: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites. Methods: A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Results: Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p < 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia (p = 0.005) and recurrent respiratory papillomatosis (p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals. Conclusions: Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment.

Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p < 0.001). At a multivariate analysis, a longer time of virological suppression (aHR 0.994, p < 0.001) and having experienced a previous virological failure (aHR 0.788, p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction.

Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single tablet regimen for the treatment of people living with HIV-1 (PLWH). We aimed to assess efficacy, safety and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Thus, we recruited an observational retrospective real-life cohort including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the provenience treatment regimen. After 48 weeks of follow-up, 147 PLWH were included and 93 were older than 55 years. PLWH with HIV-RNA < 37 copies/mL increased from 140 to 146 (p < 0.033). Among the overall population, we observed an increase in CD4+ T cells count by 30.1% (p-value < 0.001), in CD8+ T cells count by 7.1% (p-value = 0.004) and in CD4+/CD8+ ratio by 21.5% (p-value < 0.001). Lipidic profile was characterized by decreasing total cholesterol/HDL ratio by 8% (p-value < 0.001) and LDL by 6.8% (p-value = 0.007). Total body weight increased by 1.8% (p-value = 0.014) and BMI by 4.2% (p-value < 0.001), even remaining within the healthy range. Hepatic and renal profile were not altered by the switch, nor were adverse events and/or discontinuations events detected. In conclusion, BIC/FTC/TAF is effective, safe and well tolerated in real life and among PLWH older than 55.

Background. Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men. Methods. In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented. Results. 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression (p = 0.002), lower rate of onset of new anal dysplasia (p = 0.023) and lower rates of worsening of persistent lesions (p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group (p = 0.067). Conclusion. Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data.

West Africa has the highest prevalence of human immunodeficiency virus (HIV)-2 infection in the world, but a high number of cases has been recognized in Europe, India, and the United States. The virus is less transmissible than HIV-1, with sexual contacts being the most frequent route of acquisition. In the absence of specific antiretroviral therapy, most HIV-2 carriers will develop AIDS. Although, it requires more time than HIV-1 infection, CD4+ T cell decline occurs more slowly in HIV-2 than in HIV-1 patients. HIV-2 is resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and some protease inhibitors. Misdiagnosis of HIV-2 in patients mistakenly considered HIV-1-positive or in those with dual infections can cause treatment failures with undetectable HIV-1 RNA. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we focus mainly on data available and on the insight they offer about molecular epidemiology, clinical presentation, antiretroviral therapy, and diagnostic tests of HIV-2 infection.

Abstract Background Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? Discussion Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice. Conclusions Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.

Individuals affected by Coronavirus Disease 2019 (COVID-19) may experience psychiatric symptoms, including depression and suicidal ideation, that could lead to chronic impairment and a reduction in quality of life. Specifically, depressive disorder shows high incidence and may lead to chronic impairment and a reduction in the quality of life. To date, no studies on the presence of suicidality and quantitative analysis of depressive symptoms and their risk factors have yet been published. In this study, we aim to assess the prevalence of depressive symptoms and related risk factors at 3 months after discharge to home care following hospitalization for COVID-19 infection. Methods: Participants were contacted three months after hospital discharge from one of the five COVID-19 hospitals in Rome, as part of a larger project on health outcomes in COVID-19 inpatients (Long Term Neuropsychiatric Disorder in COVID-19 Project), and the Patient Health Questionnaire-9 (PHQ-9) was administered by telephone interview. Results: Of 115 participants, 14.8% (N = 17) received a PHQ-9-based diagnosis of depression, and n = 7 of them scored 1 or more on the item on suicidality. A linear regression model showed the predictive role of female sex, pulmonary chronic condition and previous mental disorder in the development of depressive disorder; the latter was confirmed also by binary logistic regression. Severity indexes of disease (length of hospitalization and intensive care treatment) were found not to be associated with the development of depressive symptoms. Conclusions: A small but clinically meaningful number of participants in the current study reported that they experienced symptoms of depression and suicidal ideation 3 months post-discharge from their COVID-19 hospitalization. In particular, given the findings that a history of prior psychiatric disorders was predictive of the development of depression symptoms, clinicians should carefully monitor for the presence of all psychiatric symptoms at follow-up visits.

Objectives: COVID-19 may show no peculiar signs and symptoms that may differentiate it from other infective or non-infective etiologies; thus, early recognition and prompt management are crucial to improve survival. The aim of this study was to describe clinical, laboratory, and radiological characteristics and outcomes of hospitalized COVID-19 patients compared to those with other infective or non-infective etiologies. Methods: We performed a prospective study from March 2020 to February 2021. All patients hospitalized for suspected or confirmed COVID-19 were prospectively recruited. All patients were evaluated according to a predefined protocol for diagnosis of suspected SARS-CoV-2 infection. The primary endpoint was evaluation of clinical, laboratory, and radiological characteristics associated or not with COVID-19 etiology at time of hospitalization in an emergency department. Results: A total of 1036 patients were included in the study: 717 (69%) patients with confirmed COVID-19 and 319 (31%) without COVID-19, hospitalized for other causes. The main causes of hospitalization among non-COVID-19 patients were acute heart failure (44%) and bacterial pneumonia (45.8%). Overall, 30-day mortality was 9% among the COVID-19 group and 35% in the non-COVID-19 group. Multivariate analysis showed variables (fever > 3 days, dry cough, acute dyspnea, lymphocytes < 1000 × 103/µL, and ferritin > 250 ng/mL) independently associated with COVID-19 etiology. A decision tree was elaborated to early detect COVID-19 patients in the emergency department. Finally, Kaplan–Meier curves on 30-day survival in COVID-19 patients during the first wave (March–May 2020, n = 289 patients) and the second wave (October–February 2021, n = 428 patients) showed differences between the two study periods (p = 0.021). Conclusions: Patients with confirmed diagnosis of COVID-19 may show peculiar characteristics at time of hospitalization that could help physicians to distinguish from other infective or non-infective etiologies. Finally, a different 30-day mortality rate was observed during different periods of the pandemic.

HIV infection is characterized by a severe deterioration of an immune cell-mediated response due to a progressive loss of CD4+ T cells from gastrointestinal tract, with a preferential loss of IL-17 producing Th cells (Th17), a specific CD4+ T cells subset specialized in maintaining mucosal integrity and antimicrobial inflammatory responses. To address the effectiveness of antiretroviral therapy (ART) in reducing chronic immunological dysfunction and immune activation of intestinal mucosa, we conducted a cross-sectional observational study comparing total IFN-γ-expressing (Th1) and IL-17-expressing (Th17) frequencies of CD4+ T lamina propria lymphocytes (LPLs) and their immune activation status between 11 male ART-naïve and 11 male long-term ART-treated people living with HIV-1 (PLWH) who underwent colonoscopy and retrograde ileoscopy for biopsies collection. Flow cytometry for surface and intracellular staining was performed. Long-term ART-treated PLWH showed lower levels of CD38+ and/or HLA-DR+ LPLs compared to ART-naïve PLWH. Frequencies of Th1 and Th17 LPLs did not differ between the two groups. Despite ART failing to restore the Th1 and Th17 levels within the gut mucosa, it is effective in increasing overall CD4+ T LPLs frequencies and reducing mucosal immune activation.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a global pandemic. Our goal was to determine whether co-infections with respiratory polyomaviruses, such as Karolinska Institutet polyomavirus (KIPyV) and Washington University polyomavirus (WUPyV) occur in SARS-CoV-2 infected patients. Oropharyngeal swabs from 150 individuals, 112 symptomatic COVID-19 patients and 38 healthcare workers not infected by SARS-CoV-2, were collected from March 2020 through May 2020 and tested for KIPyV and WUPyV DNA presence. Of the 112 SARS-CoV-2 positive patients, 27 (24.1%) were co-infected with KIPyV, 5 (4.5%) were positive for WUPyV, and 3 (2.7%) were infected simultaneously by KIPyV and WUPyV. Neither KIPyV nor WUPyV DNA was detected in samples of healthcare workers. Significant correlations were found in patients co-infected with SARS-CoV-2 and KIPyV (p < 0.05) and between SARS-CoV-2 cycle threshold values and KIPyV, WUPyV and KIPyV and WUPyV concurrently detected (p < 0.05). These results suggest that KIPyV and WUPyV may behave as opportunistic respiratory pathogens. Additional investigations are needed to understand the epidemiology and the prevalence of respiratory polyomavirus in COVID-19 patients and whether KIPyV and WUPyV could potentially drive viral interference or influence disease outcomes by upregulating SARS-CoV-2 replicative potential.