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Pyogenic spondylodiscitis (PS) is an uncommon but important infection, that represents 3-5% of all cases of osteomyelitis. The annual incidence in Europe has been estimated to be from 0.4 to 2.4/100,000. A has been reported, with peaks at age less than 20 years and in the group aged 50-70 years. The incidence of PS seems to be increasing in the last years as a result of the higher life expectancy of older patients with chronic debilitating diseases, the rise in the prevalence of immunosuppressed patients, intravenous drug abuse, and the increase in spinal instrumentation and surgery. PS is in most cases a hematogenous infection. Staphylococcus aureus is the most frequent causative microorganism, accounting for about one half of the cases of PS. Gram-negative rods are causative agents in 7-33% of PS cases. Coagulase-negative staphylococci (CoNS) have been reported in 5-16% of cases. Staphylococcus epidermidis is often related to post-operative infections and intracardiac device-related bacteremia. Unremitting back pain, characteristically worsening during the night, is the most common presenting symptom, followed by fever that is present in about one half of the cases. The mortality of PS ranges from 0 to 11%. In a significant number of cases, recrudescence, residual neurological defects or persistent pain may occur. [ABSTRACT FROM AUTHOR]

Background: Transmitted drug resistance (TDR) is still a critical aspect for the management of individuals living with HIV-1. Thus, its evaluation is crucial to optimize HIV care., Methods: Overall, 2386 HIV-1 protease/reverse transcriptase and 1831 integrase sequences from drug-naïve individuals diagnosed in north and central Italy between 2015 and 2021 were analysed. TDR was evaluated over time. Phylogeny was generated by maximum likelihood. Factors associated with TDR were evaluated by logistic regression., Results: Individuals were mainly male (79.1%) and Italian (56.2%), with a median (IQR) age of 38 (30-48). Non-B infected individuals accounted for 44.6% (N = 1065) of the overall population and increased over time (2015-2021, from 42.1% to 51.0%, P = 0.002). TDR prevalence to any class was 8.0% (B subtype 9.5% versus non-B subtypes 6.1%, P = 0.002) and remained almost constant over time. Overall, 300 transmission clusters (TCs) involving 1155 (48.4%) individuals were identified, with a similar proportion in B and non-infected individuals (49.7% versus 46.8%, P = 0.148). A similar prevalence of TDR among individuals in TCs and those out of TCs was found (8.2% versus 7.8%, P = 0.707).By multivariable analysis, subtypes A, F, and CFR02_AG were negatively associated with TDR. No other factors, including being part of TCs, were significantly associated with TDR., Conclusions: Between 2015 and 2021, TDR prevalence in Italy was 8% and remained almost stable over time. Resistant strains were found circulating regardless of being in TCs, but less likely in non-B subtypes. These results highlight the importance of a continuous surveillance of newly diagnosed individuals for evidence of TDR to inform clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

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 < 0.001), sore throat (2.14; 1.27-3.59, p = 0.004), and peri-anal lesions (2.91; 1.93-4.37, p < 0.001). There was a significant difference (p = 0.003) between the median Ct-value in the upper respiratory tract for patients presenting with either mild (35.15; IQR 28.77-42.01) or severe infection (31.00; 25.00-42.01). The risk of developing severe disease decreased by approximately 5% per Ct increase (0.95; 0.91-0.98; p = 0.005). The disease lasted longer in the case of proctitis (+4.78 days; 1.95-7.61, p = 0.001), sore throat (+3.12; 0.05-6.20, p = 0.046), extended rash (+3.42; 0.55-6.28, p = 0.020), as well as in PLWH with a low CD4 count (+12.51; 6.79-18.22, p < 0.001)., Interpretation: The identification of predictors of severe or prolonged disease and the direct association MPXV Ct-value in the upper respiratory tract and disease severity could be useful in establishing proper management and early treatment of new mpox cases., Funding: ICONA Foundation; Italian Ministry of Health "Ricerca Corrente Linea 2", INMI Lazzaro Spallanzani IRCCS., Competing Interests: Declaration of interests The authors declare no competing interests for this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The 2022 global mpox outbreak was driven by human-to-human transmission, but modes of transmission by sexual relationship versus sexual contact remain unclear. We evaluated sexual transmission of mpox by using monkeypox virus (MPXV) G2R-mRNA as a marker of ongoing viral replication through in vitro experiments. We analyzed clinical samples of 15 MPXV-positive patients in Italy from different biological regions by using the setup method. The presence of MPXV DNA, MPXV G2R-mRNA, or both in all analyzed lesion swab samples, independent of viral load, confirmed a higher infectivity risk from skin lesions. Positivity for MPXV G2R-mRNA in nasopharyngeal swabs was associated with high MPXV load, whereas positive results for MPXV G2R-mRNA were obtained only in the 2 semen samples with the lowest MPXV loads. Our results suggest that close or skin-to-skin contact during sexual intercourse is the main route of sexual transmission and that semen is a minor driver of infection, regardless of MPXV load.

Objective . We aimed to report the real-world use and outcomes over time in immunocompromised individuals receiving tixagevimab/cilgavimab (T/C) pre-exposure prophylaxis (PrEP). Methods . This observational study included participants who received T/C PrEP, categorized into three groups: (i) No COVID-19 (NoC), i.e., participants who never had COVID-19; (ii) Hybrids (H), i.e., participants who had COVID-19 before PrEP; and (iii) Break-through Infections (BTIs), i.e., participants who had COVID-19 after PrEP. The study measured several immune markers at the administration of T/C (T0) at 3 (T1), 6 (T2), and 9 (T3) months afterward. These markers included: anti-receptor-binding domain (RBD) IgG antibodies; BA.5-neutralizing antibodies (nAbs); mucosal IgG; and T cell immunity. The incidence rate ratios for BTIs were analyzed using a Poisson regression model. Results . A total of 231 participants with a median age of 63 years (IQR 54.0-73.0). were included. Among these, 84% had hematological diseases and received a median of three vaccine doses. N = 72 participants belonged to the NoC group, N = 103 to the H group, and n = 56 to the BTI group (24%), with most BTIs being mild/moderate. The incidence rate (IR) of BTIs was 4.2 per 100 patient-months (95% CI 3.2-5.4), with no associated risk factors identified. There was a significant increase in anti-RBD IgG levels 3 months after the T/C administration in all groups, followed by a decline at 6 months, whereas at the same time points, geometric mean titers (GMTs) of anti-BA.5 nAbs were low for all groups and were around or below the detection threshold. No significant changes were observed in IFN-γ levels. The mucosal immune response was observed only 3 months after the PrEP administration. Conclusion . We provided a real-world experience model on the clinical efficacy of T/C PrEP in preventing severe COVID-19 during the Omicron wave through a comprehensive virological and immunological study. While waiting for the arrival of new monoclonal antibodies that can effectively neutralize the most recent variants, T/C PrEP remains the only viable strategy in the available armamentarium today to prevent COVID-19 complications in an extremely fragile population with suboptimal immune responses to COVID-19 vaccines.

Objectives: To investigate whether SARS-CoV-2 messenger RNA (mRNA) vaccination has an impact on HIV-related viro-immunological parameters., Methods: People with HIV (PWH) in the VAXICONA-ORCHESTRA cohort who received one or more doses of SARS-CoV-2 mRNA vaccine and for whom paired measures of immuno-virological markers (viral load, clusters of differentiation [CD]4, and CD8 count 1 month before and after a vaccine dose [VD]) were available were included. Paired t-test and generalized estimating equation linear regression analyses were used to study changes over ± 1 month around the VD. Subgroup analyses were performed., Results: A total of 510 PWH were enrolled: the median age was 55 years (interquartile range 46-60 years), the CD4 and CD8 count were 489 (287-719) and 790 (59-1104) cells/mm 3 , respectively, and 81% received three VDs. After a median of 28 (3-53) days from VD, CD4 count increased by +15 cells/mm 3 (SD ± 129.7, P = 0.001) and CD8 by +12 (±250.5, P = 0.199) and the viral load decreased by -0.11 log 10 (±0.88, P = 0.001). Similar results were observed after restricting the analysis to viro-suppressed PWH, with CD4 ≤200/mm 3 , more than 6 months of antiretroviral therapy before VD and after excluding previous COVID-19., Conclusions: A small significant increase in CD4 count and a negligible drop in HIV RNA were observed. Our findings are consistent with the hypothesis that SARS-CoV-2 mRNA vaccine can prime CD4 T spike-specific cells, even in the more immuno-compromised PWH., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Whether pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab 150 mg/150 mg (T/C) in individuals with hematologic disease (HD) may lead to a reduced risk of SARS-CoV-2 breakthrough infection (BTI)/hospitalization, or death in the Omicron era remains to be established., Methods: An observational study included participants with HD who received PrEP. BTIs were defined as SARS-CoV-2 positivity by reverse transcription-polymerase chain reaction. The incidence of BTIs (95% CI) and of BTIs/hospitalization/death was calculated using the Kaplan-Meier method and as the number of BTIs per 100 person-years of follow-up according to the circulating variant of concern (VoC). A Poisson regression model was used to evaluate the association between the rate of incidence and circulating VoCs after controlling for demographics and clinical factors., Results: We included 550 HD patients: 71% initiated T/C PrEP when BA.5 was the most prevalent, followed by XBB/EG, BA.2, and BA.1 (19%, 7%, and 3%, respectively). Overall, the 1-year incidence estimate of BTIs/hospitalization/death was 24% (18.7-29.4%). A greater risk of incident infections was observed when BA.5 and XBB/EG sub-lineages circulated (aRR 5.05 [2.17, 11.77]; P < .001 and 3.82 [1.50, 9.7]; P = 0.005, compared to BA.1, respectively)., Conclusions: The 1-year incidence of SARS-CoV-2 BTIs/hospitalization/death was 24% which is in line with what was observed in other similar studies. The risk appeared to be higher when more recent Omicron sub-lineages were circulating suggesting a reduction of in vitro neutralization., Competing Interests: Declaration of competing interest All authors report no conflicts of interest relevant to this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Despite emerging evidence indicating that molecular SARS-CoV-2 tests performed on saliva have diagnostic sensitivity and specificity comparable to those observed with nasopharyngeal swabs (NPSs), most in vivo follow-up studies on the efficacy of drugs against SARS-CoV-2 have been performed on NPSs, not considering saliva as a possible alternative matrix. For this reason, in this study, we used, in parallel, saliva and NPS samples for the detection of SARS-CoV-2 by real-time RT-PCR in patients receiving Tixagevimab/Cilgavimab, Nirmatrelvir/Ritonavir, or Sotrovimab as a treatment against SARS-CoV-2. Our results showed a good correlation between the NPS and saliva samples for each drug; moreover, comparable changes in the cycle threshold (Ct) levels in saliva and NPSs were observed both 7 days and 30 days after treatment, thus confirming that the saliva represents a good matrix for in vivo follow-up studies verifying the effectiveness of treatments against SARS-CoV-2., Competing Interests: The authors declare no conflicts of interest.

Since spring 2022, the global epidemiology of the monkeypox virus (MPXV) has changed. The unprecedented increase of human clade II MPXV cases worldwide heightened concerns about this emerging zoonotic disease. We analysed the positivity rates, viral loads, infectiousness, and persistence of MPXV DNA for up to 4 months in several biological samples from 89 MPXV-confirmed cases. Our data showed that viral loads and positivity rates were higher during the first two weeks of symptoms for all sample types. Amongst no-skin-samples, respiratory specimens showed higher MPXV DNA levels and median time until viral clearance, suggesting their usefulness in supporting MPXV diagnosis, investigating asymptomatic patients, and monitoring viral shedding. Infectious virus was cultured from respiratory samples, semen, and stools, with high viral loads and collected within the first 10 days. Notably, only one saliva and one semen were found positive for viral DNA after 71 and 31 days from symptoms, respectively. The focus on bloodstream samples showed the best testing sensitivity in plasma, reporting the overall highest MPXV DNA detection rate and viral loads during the 3-week follow-up as compared to serum and whole-blood. The data here presented can be useful for MPXV diagnostics and a better understanding of the potential alternative routes of its onward transmission., (© 2024. The Author(s).)

Objectives: The multifactorial dynamic perfusion index was recently introduced as a predictor of cardiac surgery-associated acute kidney injury. The multifactorial dynamic perfusion index was developed based on retrospective data retrieved from the patient files. The present study aims to prospectively validate this index in an external series of patients, through an on-line measure of its various components., Methods: Inclusion criteria were adult patients undergoing cardiac surgery with cardiopulmonary bypass. Data collection included preoperative factors and cardiopulmonary bypass-related factors. These were collected on-line using a dedicated monitor. Factors composing the multifactorial dynamic perfusion index are the nadir haematocrit, the nadir oxygen delivery, the time of exposure to a low oxygen delivery, the nadir mean arterial pressure, cardiopulmonary bypass duration, the use of red blood cell transfusions and the peak arterial lactates., Results: Two hundred adult patients were investigated. The multifactorial dynamic perfusion index had a good (c-statistics 0.81) discrimination for cardiac surgery-associated acute kidney injury (any stage) and an excellent (c-statistics 0.93) discrimination for severe patterns (stage 2-3). Calibration was modest for cardiac surgery-associated acute kidney injury (any stage) and good for stage 2-3. The use of vasoconstrictors was an additional factor associated with cardiac surgery-associated acute kidney injury., Conclusions: The multifactorial dynamic perfusion index is validated for discrimination of cardiac surgery-associated acute kidney injury risk. It incorporates modifiable risk factors, and may help in reducing the occurrence of cardiac surgery-associated acute kidney injury., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed during the COVID-19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS-CoV-2 lineages characterized by a higher transition/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data (GISAID) and International Nucleotide Sequence Database Collaboration (INSDC) databases. Here, we assessed the drug effects by SARS-CoV-2 whole-genome sequencing on 38 molnupiravir-treated persistently positive COVID-19 outpatients tested before and after treatment. Seventeen tixagevimab/cilgavimab-treated outpatients served as controls. Mutational analyses confirmed that SARS-CoV-2 exhibits an increased transition/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G->A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Competing Interests: Competing interests: The authors declare no conflict of Interest.

We estimated the dynamics of the neutralizing response against XBB sublineages and T cell response in persons with HIV (PWH) with previous AIDS and/or CD4 < 200/mm 3 receiving the bivalent original strain/BA.4-5 booster dose in fall 2022. Samples were collected before the shot (Day 0), 15 days, 3, and 6 months after. PWH were stratified by immunization status: hybrid immunity (HI; vaccination plus COVID-19) versus nonhybrid immunity (nHI; vaccination only). Fifteen days after the booster, 16% and 30% of PWH were nonresponders in terms of anti-XBB.1.16 or anti-EG.5.1 nAbs, respectively. Three months after, a significant waning of anti-XBB.1.16, EG.5.1 and -XBB.1 nAbs was observed both in HI and nHI but nAbs in HI were higher than in nHI. Six months after both HI and nHI individuals displayed low mean levels of anti-XBB.1.16 and EG.5.1 nAbs. Regarding T cell response, IFN-γ values were stable over time and similar in HI and nHI. Our data showed that in PWH, during the prevalent circulation of the XBB.1.16, EG.5.1, and other XBB sublineages, a mRNA bivalent vaccine might not confer broad protection against them. With a view to the 2023/2024 vaccination campaign, the use of the monovalent XBB.1.5 mRNA vaccine should be urgently warranted in PWH to provide adequate protection., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR p < 0.05). Functional analysis identified 163 target mRNAs involved in promoting angiogenesis activation in AHI versus CHI through the action of hsa-miR10b-5p, hsa-miR1290, hsa-miR1-3p, and hsa-miR296-5p. The viral miRNAs detected, all belonging to herpesviruses, accounted for only 0.014% of total reads. The present data suggest that AHI patients exhibit strong innate immune activation through the upregulation of hsa-miR-122-5p and early activation of angiogenesis. More specific investigations are needed to study the role of viral miRNAs in HIV pathogenesis.

Introduction: Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm., Methods: This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality., Results: A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO 2 /FiO 2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data., Conclusion: The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cozzi-Lepri, Borghi, Rotundo, Mariani, Ferrari, Del Borgo, Bai, Colletti, Miraglia, Torti, Cattelan, Cenderello, Berruti, Tascini, Parruti, Coladonato, Gori, Marchetti, Lichtner, Coppola, Sorace, D'Abramo, Mazzotta, Guaraldi, Franceschini, Meschiari, Sarmati, Antinori, Nicastri and Mussini.)

Background: COVID-19 pandemic challenged the UNAIDS 90-90-90 targets. How the COVID-19 pandemic affected HIV retention in care and whether it has disproportionally affected migrant people with HIV (PWH) remained to be investigated., Methods: PWH in ICONA Cohort in follow-up in each of the study periods were included: 01/09/2019-29/02/2020 (pandemic period) and 01/03/2018-31/08/2018 (historical period, as a control). Risk of temporary loss to follow-up (LTFU, defined as no data recorded for a person for one year) was analyzed by logistic regression, with migrant status as the main exposure variable. Difference in difference (DID) analysis was applied to evaluate the effect of COVID-19 pandemic in the different risk of LTFU between natives and migrants., Results: 8864 (17.1% migrants) and 8071 (16.8% migrants) PWH constituted the pandemic and the historical period population, respectively. Proportion of PWH defined as LTFU in the pandemic period was 10.5% in native and 19.6% in migrant PWH. After controlling for age, sex and geographical location of enrolling site, risk of temporary LTFU was higher for migrants than native PWH [adjusted odds ratio 1.85 (95%CI 1.54-2.22)] in pandemic period. In PWH contributing to both periods, LTFU was 9.0% (95% CI 8.3-9.8) in natives vs 17.0% (95% CI 14.7-19.4) in migrants during the pandemic. Instead, LTFU was 1.2% (95%CI 0.9, 1.5) in natives vs 2.2% (95% CI 1.3-3.1) in migrants during the historical period, with a resulting DID of 7.0% (95% CI 4.4-9.6)., Conclusions: A greater proportion of LTFU in migrant PWH was observed in both periods, which remained unaltered over time. Interventions to reduce LTFU of migrants are necessary., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roberta Gagliardini reports payments to her institution from Gilead Sciences, speakers’ honoraria/educational activities for ViiV Healthcare, Merck Sharp and Dohme and Gilead Sciences, advisor for Theratechnologies, Janssen-Cilag and Gilead Sciences. Andrea Giacomelli received consultancy fees from Mylan and Janssen. Speaker honoraria from ViiV, Gilead, and MSD. Educational and grant support from Gilead and ViiV. Antonella D'arminio Monforte is a consultant or participated in advisory boards sponsored by Gilead Sciences, ViiV Healthcare, Janssen-Cilag, GSK, Merck Sharp & Dohme and received research grants from Gilead Sciences and ViiV Healthcare. Enrico Girardi received research grants from Gilead and Mylan and speaker fees from Gilead and ViiV unrelated to the present study. All other authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The recent multi-country outbreak of the zoonotic monkeypox virus (MPXV) infection in humans without an epidemiological link with endemic areas has raised concerns about the route of transmission. Since the infection spread largely among men who have sex with men who, in most cases, presented primary lesions of the genital and oral mucosa, sexual transmission has been proposed. In the present study, we retrospectively evaluated specimens of vesicular lesions collected from the skin and genital tract of 35 patients (23 positive and 12 negative) presenting at our Institute for monkeypox (mpox) diagnosis by using a novel molecular syndromic vesicular virus panel (VVP) assay. All MPXV-positive samples but one was confirmed; however, the viral syndromic analysis revealed that 8.6% of them were coinfected with one or more viruses, and 17% had at least a virus different from the MPXV. The percentage of coinfections increased to more than 25% when nonviral pathogens, such as gonorrhea and syphilis, were also considered. These results show the usefulness of syndromic diagnosis in cases where MPXV is suspected (and vice versa) and at the same time highlight that the broader screening of sexually transmitted infections in the population with high-risk sexual behavior is critical to ensure a complete etiology and appropriate treatment.

A 59-year-old treatment-naive patient with advanced HIV infection presented with a severe and protracted course of mpox (formerly known as monkeypox) that did not respond to the current mpox treatment options. The patient worsened clinically, and developed new mucocutaneous lesions and necrotic evolution of pre-existing ones, along with multiple bilateral lung nodules and the appearance of a tracheal necrotic lesion. Although severe forms of mpox have been observed in people with severe immune system deficiency, including those with advanced HIV presentation, the immunological mechanisms underlying this observation have not yet been fully explained. To our knowledge, this is the first account of a necrotising mpox in a person living with HIV, with viral shedding for more than 11 months and a comprehensive immunological description. Moreover, we documented the virus' persistence by detecting mpox virus DNA from multiple sites and quantified anti-monkeypox virus IgA, IgM, IgG, and neutralising antibodies in serum samples. The severe HIV-driven immune depression and the presence of other co-infections might skew and impair immune responses, thus contributing to the persistence of monkeypox virus infection. Further investigations of immune responses to monkeypox virus infection in people with severe immunosuppression are required to improve management and prevention., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated., Methods: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested., Primary End-Point: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence., Results: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5)., Conclusions: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: During HIV infection, effective combined antiretroviral therapy suppresses viral replication and restores the number of circulating CD4+ T cells. However, 15%-30% of treated patients show a discordant response to combined antiretroviral therapy. Myeloid-derived suppressor cells (MDSC) are expanded in HIV+ patients; to better understand the role of MDSC on CD4 T-cell recovery, we evaluated the frequency of MDSC in HIV+ patients under combined antiretroviral therapy and its association with immunologic response., Methods: We enrolled 60 HIV+ patients, including complete responders (R, n = 44), virologic nonresponders (VNR, n = 5), and immunologic nonresponders (INR, n = 11). The frequency of circulating MDSC and the percentage of activated and naïve CD4 T cells were evaluated by flow cytometry. Plasmatic cytokine levels were analyzed by automated ELISA., Results: As previously observed, polymorphonuclear MDSC (PMN-MDSC) frequency was higher in HIV+ patients compared with healthy donors. Furthermore, PMN-MDSC percentage was higher in INR than R patients, and a significant association between MDSC frequency and immunologic failure was confirmed by a receiver operator characteristic analysis. Accordingly, an inverse correlation was found between the percentages of PMN-MDSC and naïve CD4 T cells. A positive correlation was observed between PMN-MDSC frequency and the percentage of human leucocyte antigen locus DR + CD4 T cells and the plasmatic level of IL-1β and IL-8., Conclusion: Our results show that a high frequency of PMN-MDSC persists in INR, possibly because of immune activation, contributing to CD4 T-cell recovery failure. These findings further highlight the detrimental role of MDSC during HIV infection, suggesting these cells as a possible new therapeutic target., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)