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1. Incidence, healthcare resource utilization and costs of hospitalized patients with tick-borne encephalitis (TBE) in Italy

Author

Renzo Scaggiante, Liliana Guadagni, Massimiliano Orso, Daniela d’Angela, Ciro Carrieri, Barbara Polistena, Federico Spandonaro, Ilaria Bertoldi, Andreas Pilz, Katharina Schley, and Raffaella Iantomasi

Subjects
Tick-borne encephalitis (TBE), Hospitalization, Epidemiology, Italy, Burden of disease, Economic burden, Infectious and parasitic diseases, RC109-216
Abstract

Objective: Our study's objective was to assess the incidence trends and healthcare resource utilization of hospitalizations for Tick-Borne Encephalitis (TBE) and associated costs in Italy in order to improve public awareness and preventive measures. Methods: This retrospective observational study was based on the Italian Ministry of Health's Hospital Discharge Record (HDR) database. Data were gathered across Italy from 2015 to 2019, selecting hospitalizations with ICD-9 code 063 related to TBE, both in primary and secondary diagnoses. For each year, we collected the following variables: number of hospitalizations, hospitalization rate, mortality rate, mean length of hospital stay, hospital ward, and cost of hospitalization. Results: There were a total of 237 hospitalizations from 2015 to 2019; 62 % of those were male. The lowest number of TBE hospitalizations was in 2015 (21 cases, corresponding to 0.35 per million inhabitants), the highest in 2019 (64 cases, 1.04 per million inhabitants). The summer months saw a greater than average number of hospitalizations. For the years analyzed, the cumulative number of cases peaked in June (54 cases), July (46 cases), and August (35 cases). There were only two deaths registered in our study sample. TBE cases were mostly localized in the North-Eastern regions of Italy. TBE incidence during the study period in the most affected areas were: Autonomous Province of Trento, ranging from 11.2 to 42.3 per million inhabitants, Autonomous Province of South Tyrol, from 0 to 21.1 per million inhabitants, and Veneto Region, from 2.6 to 4.5 per million inhabitants. In the study period, the average length of hospital stay was largely stable ranging from 10.6 days to 12.8 days, with related costs ranging from 5,813.7 € to 7,352.5 €. Conclusions: According to our data, the majority of TBE hospitalizations occur in North-East Italy with an increasing trend over the analyzed period. Even though Italy has fewer TBE cases than other neighboring European countries, the health and economic impact can be high in the affected areas.

Published
2024
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2. Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

Author

Gabriele Martelloni, Alessio Turchi, Chiara Fallerini, Andrea Degl’Innocenti, Margherita Baldassarri, Simona Olmi, Simone Furini, Alessandra Renieri, GEN-COVID Multicenter study, Francesca Mari, Sergio Daga, Ilaria Meloni, Mirella Bruttini, Susanna Croci, Mirjam Lista, Debora Maffeo, Elena Pasquinelli, Giulia Brunelli, Kristina Zguro, Viola Bianca Serio, Enrica Antolini, Simona Letizia Basso, Samantha Minetto, Giulia Rollo, Martina Rozza, Angela Rina, Rossella Tita, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Elena Bargagli, Laura Bergantini, Miriana d’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Arianna Emiliozzi, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Maria Lorubbio, Alessandro Pancrazzi, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Mario U. Mondelli, Stefania Mantovani, Raffaele Bruno, Marco Vecchia, Marcello Maffezzoni, Enrico Martinelli, Massimo Girardis, Stefano Busani, Sophie Venturelli, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Carlo Pallotto, Saverio Giuseppe Parisi, Monica Basso, Sandro Panese, Stefano Baratti, Pier Giorgio Scotton, Francesca Andretta, Mario Giobbia, Renzo Scaggiante, Francesca Gatti, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Giuseppe Merla, Gabriella Maria Squeo, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Alex Di Florio, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Cristina Mussini, Luisa Tavecchia, Lia Crotti, Gianfranco Parati, Roberto Menè, Maurizio Sanarico, Marco Gori, Francesco Raimondi, Alessandra Stella, Filippo Biscarini, Tiziana Bachetti, Maria Teresa La Rovere, Maurizio Bussotti, Serena Ludovisi, Katia Capitani, Simona Dei, Sabrina Ravaglia, Annarita Giliberti, Giulia Gori, Rosangela Artuso, Elena Andreucci, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Giulia Micheli, Marco Falcone, Donato Urso, Giusy Tiseo, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Alessio Bellucci, Marta Colaneri, Patrizia Casprini, Cristoforo Pomara, Massimiliano Esposito, Roberto Leoncini, Michele Cirianni, Lucrezia Galasso, Marco Antonio Bellini, Chiara Gabbi, and Nicola Picchiotti

Subjects
COVID-19, host genetics, integrated polygenic score, genetic algorithm, logistic regression, genetic science modeling, Genetics, QH426-470
Abstract

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.

Published
2024
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3. Patterns of Transmitted Drug Resistance Mutations and HIV-1 Subtype Dynamics in ART-Naïve Individuals in Veneto, Italy, from 2017 to 2024

Author

Nicholas Geremia, Monica Basso, Andrea De Vito, Renzo Scaggiante, Mario Giobbia, Giuliana Battagin, Federico Dal Bello, Maria Teresa Giordani, Stefano Nardi, Marina Malena, Annamaria Cattelan, and Saverio Giuseppe Parisi

Subjects
HIV, genotypic resistance testing, transmitted drug resistance mutations, HIV subtypes, HIV resistance, Microbiology, QR1-502
Abstract

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity to inform treatment strategies effectively. We included all adult ART-naïve people with HIV (PWH) from seven infectious disease units in Veneto, Italy. We collected the genotypic resistance testing conducted to predict drug susceptibility and subtype distribution using the Stanford HIVdb algorithm. We included 762 PWH, showing a slight but statistically significant decline in the B subtype among Italian PWH (p = 0.045) and an increase in non-B subtypes among foreigners, though it was not statistically significant (p = 0.333). The most frequent mutations were in Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), especially in non-B subtypes, with a notable rise from 10.7% in 2017–2019 to 15.5% in 2020–2024. Notably, TDRMs were consistently detected, highlighting an ongoing challenge despite the stable prevalence observed over the years. In addition, the data revealed a concerning rise in mutations against newer drug classes, such as integrase inhibitors. Conclusively, the study underscores the necessity of continuous surveillance of HIV subtypes and resistance patterns to adapt ART regimens optimally. Despite the stable levels of drug resistance, the emergence of resistance against newer drugs necessitates ongoing vigilance and possible adjustment in treatment protocols to enhance clinical outcomes and manage HIV drug resistance effectively.

Published
2024
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4. Faster decay of neutralizing antibodies in never infected than previously infected healthcare workers three months after the second BNT162b2 mRNA COVID-19 vaccine dose

Author

Ilaria Vicenti, Monica Basso, Francesca Gatti, Renzo Scaggiante, Adele Boccuto, Daniela Zago, Eliana Modolo, Filippo Dragoni, Saverio Giuseppe Parisi, and Maurizio Zazzi

Subjects
Healthcare workers, BNT162b2 mRNA COVID-19 vaccine, Neutralizing antibodies, COVID-19, Mild disease, Asymptomatic, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: This study aimed to describe the longitudinal evolution of neutralizing antibody titres (NtAb) in three different cohorts of healthcare workers (HCWs), including vaccinated HCWs with and without a previous SARS-CoV-2 infection and previously infected unvaccinated HCWs. COVID-19 was mild or asymptomatic in those experiencing infection. Methods: NtAb was tested before BNT162b2 mRNA COVID-19 vaccine (V0), 20±2 days after the first dose (V1_20), 20±3 days (V2_20) and 90±2 days (V2_90) after the second dose in vaccinated HCWs and after about 2 months (N_60), 10 months (N_300) and 13 months (N_390) from natural infection in unvaccinated HCWs. NtAb were measured by authentic virus neutralization with a SARS-CoV-2 B.1 isolate circulating in Italy at HCW enrolment. Results: Sixty-two HCWs were enrolled. NtAb were comparable in infected HCWs with no or mild disease at all the study points. NtAb of uninfected HCWs were significantly lower with respect to those of previously infected HCWs at V1_20, V2_20 and V2_90. The median NtAb fold decrease from V2_20 to V2_90 was higher in the uninfected HCWs with respect to those with mild infection (6.26 vs 2.58, p=0.03) and to asymptomatic HCWs (6.26 vs 3.67, p=0.022). The median Nabt at N_390 was significantly lower than at N_60 (p=0.007). Conclusions: In uninfected HCWs completing the two-dose vaccine schedule, a third mRNA vaccine dose is a reasonable option to counteract the substantial NtAb decline occurring at a significantly higher rate compared with previously infected, vaccinated HCWs. Although low, Nabt were still at a detectable level after 13 months in two-thirds of previously infected and unvaccinated HCWs.

Published
2021
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5. HIV tropism switch in archived DNA of HIV-HCV subjects successfully treated with direct-acting antivirals for HCV infection

Author

Monica Basso, Daniela Zago, Renzo Scaggiante, Silvia Cavinato, Irene Pozzetto, Camilla Stagni, Beatrice Parisatto, Anna Maria Cattelan, Giuliana Battagin, Loredana Sarmati, and Saverio Giuseppe Parisi

Subjects
Medicine, Science
Abstract

Abstract We described short-term HIV tropism changes occurring in peripheral blood mononuclear cells and the correlations with HIV DNA value in HIV-HCV co-infected patients cured for HCV disease and with undetectable HIV viremia or residual viremia (RV). Plasma HIV RNA, cellular HIV DNA and tropism were evaluated pre-HCV treatment (baseline, BL) and at 12(T1) and 24(T2) weeks after HCV treatment start. V3 sequences were interpreted using Geno2pheno and classified as R5 only if all three sequences had an FPR ≥ 10% and as X4 when at least one replicate sequence had an FPR

Published
2021
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6. Single-dose BNT162b2 mRNA COVID-19 vaccine significantly boosts neutralizing antibody response in health care workers recovering from asymptomatic or mild natural SARS-CoV-2 infection

Author

Ilaria Vicenti, Francesca Gatti, Renzo Scaggiante, Adele Boccuto, Daniela Zago, Monica Basso, Filippo Dragoni, Maurizio Zazzi, and Saverio Giuseppe Parisi

Subjects
Health care workers, BNT162b2 mRNA COVID-19 vaccine, Neutralizing antibody response, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: To measure SARS-CoV-2 neutralizing antibody (NtAb) titres in previously infected or uninfected health care workers who received one or two doses of BNT162b2 mRNA COVID-19 vaccine. Methods: NtAbs were titrated as dose-inhibiting 50% virus replication (ID50) by live virus microneutralization. We evaluated 41 health care workers recovering from mild or asymptomatic infection at first vaccination dose (T1_inf) and 21 days later (T2_inf). Sixteen uninfected health care workers were evaluated 20 days after first dose (T2_uninf) and 20 days after second vaccine dose (T3_uninf). Results: At T2_inf, but not at T1_inf, there was a significant correlation between days from diagnosis (median 313, interquartile range 285–322) and NtAb levels (P = 0.011). NtAb titres increased at T2_inf with respect to T1_inf (1544 (732–2232) vs 26 (10–88), P < 0.001). Similarly, there was a significant increase in NtAb titres at T3_uninf compared with T2_uninf (183 (111–301) vs 5 (5–15), P < 0001). However, NtAb levels at T2_inf were significantly higher than those at T2_uninf and T3_uninf (P < 0.0001 for both analyses). Conclusions: A single vaccination in people with mild or asymptomatic previous infection further boosts SARS-CoV-2 humoral immunity to levels higher than those obtained by complete two-vaccination in uninfected subjects.

Published
2021
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7. Role of HBcAb Positivity in Increase of HIV-RNA Detectability after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Months 48 Results of a Multicenter Italian Cohort

Author

Vincenzo Malagnino, Romina Salpini, Elisabetta Teti, Mirko Compagno, Ludovica Ferrari, Tiziana Mulas, Valentina Svicher, Marta Zordan, Monica Basso, Giuliana Battagin, Sandro Panese, Maria Cristina Rossi, Renzo Scaggiante, Daniela Zago, Marco Iannetta, Saverio Giuseppe Parisi, Massimo Andreoni, and Loredana Sarmati

Subjects
HIV/HBV, 2DR, HBcAb, hepatitis B virus (HBV), Occult Hepatitis B Infection (OBI), Microbiology, QR1-502
Abstract

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

Published
2023
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8. Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: complexity and vaccine implications

Author

Saverio Giuseppe Parisi, Monica Basso, Renzo Scaggiante, Samantha Andreis, Carlo Mengoli, Mario Cruciani, Claudia Del Vecchio, Nicola Menegotto, Daniela Zago, Loredana Sarmati, Massimo Andreoni, and Giorgio Palù

Subjects
High risk HPV, Men who have sex with men, Anal, Oral, HIV infection, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM). Methods We described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24 months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II. Results Median age was 44 years (IQR 36–53), median CD4+ cell count at nadir was 312 cells/mm3 (IQR 187–450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p = 0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p = 0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p = 0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up. Conclusions We believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site.

Published
2019
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9. Long-Term Longitudinal Analysis of Neutralizing Antibody Response to Three Vaccine Doses in a Real-Life Setting of Previously SARS-CoV-2 Infected Healthcare Workers: A Model for Predicting Response to Further Vaccine Doses

Author

Saverio Giuseppe Parisi, Carlo Mengoli, Monica Basso, Ilaria Vicenti, Francesca Gatti, Renzo Scaggiante, Lia Fiaschi, Federica Giammarino, Marco Iannetta, Vincenzo Malagnino, Daniela Zago, Filippo Dragoni, and Maurizio Zazzi

Subjects
COVID-19, long-term follow-up, third vaccine dose, BNT162b2 mRNA vaccine, authentic virus neutralization, healthcare workers, Medicine
Abstract

We report the time course of neutralizing antibody (NtAb) response, as measured by authentic virus neutralization, in healthcare workers (HCWs) with a mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection diagnosed at the onset of the pandemic, with no reinfection throughout and after a three-dose schedule of the BNT162b2 mRNA vaccine with an overall follow-up of almost two years since infection. Forty-eight HCWs (median age 47 years, all immunocompetent) were evaluated: 29 (60.4%) were asymptomatic. NtAb serum was titrated at eight subsequent time points: T1 and T2 were after natural infection, T3 on the day of the first vaccine dose, T4 on the day of the second dose, T5, T6, and T7 were between the second and third dose, and T8 followed the third dose by a median of 34 days. NtAb titers at all postvaccination time points (T4 to T8) were significantly higher than all those at prevaccination time points (T1 to T3). The highest NtAb increase was following the first vaccine dose while subsequent doses did not further boost NtAb titers. However, the third vaccine dose appeared to revive waning immunity. NtAb levels were positively correlated at most time points suggesting an important role for immunogenetics.

Published
2022
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10. Comparable Post-Vaccination Decay of Neutralizing Antibody Response to Wild-Type and Delta SARS-CoV-2 Variant in Healthcare Workers Recovered from Mild or Asymptomatic Infection

Author

Ilaria Vicenti, Monica Basso, Filippo Dragoni, Francesca Gatti, Renzo Scaggiante, Lia Fiaschi, Saverio G. Parisi, and Maurizio Zazzi

Subjects
COVID-19, vaccination, Delta, BNT162b2 vaccine, neutralizing antibody, Medicine
Abstract

We described the long-term decay of neutralizing antibody (NtAb) to the wild-type and Delta SARS-CoV-2 variant after three antigen stimulations (mild or asymptomatic natural infection followed by two doses of the BNT162b2 mRNA vaccine after a median of 296 days) in immunocompetent healthcare workers (HCWs). Live virus microneutralization against the B.1 and Delta SARS-CoV-2 variants was performed in VERO E6 cell cultures. The median NtAb titers for B.1 and Delta were comparable and highly correlated at both 20 and 200 days after the second vaccine dose in the 23 HCWs enrolled (median age, 46 years). A small group of naturally infected unvaccinated HCWs had comparable NtAb titers for the two strains after a median follow-up of 522 days from infection diagnosis. The NtAb response to the Delta VoC appears to follow the same long-term dynamics as the wild-type response regardless of the vaccinal boost; data collected after three antigen stimulations (natural infection followed by two doses of the BNT162b2 mRNA vaccine) may be helpful for tailoring the continuous monitoring of vaccine protection against SARS-CoV-2 variants over time.

Published
2022
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11. Cytomegalovirus, Epstein-Barr virus and human herpesvirus 8 salivary shedding in HIV positive men who have sex with men with controlled and uncontrolled plasma HIV viremia: a 24-month longitudinal study

Author

Monica Basso, Samantha Andreis, Renzo Scaggiante, Elisa Franchin, Daniela Zago, Maria Angela Biasolo, Claudia Del Vecchio, Carlo Mengoli, Loredana Sarmati, Massimo Andreoni, Giorgio Palù, and Saverio Giuseppe Parisi

Subjects
HIV positive MSM, Longitudinal persistence of salivary shedding, EBV DNA, HHV-8 DNA, CMV DNA, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background This longitudinal study described Cytomegalovirus (CMV) DNA, Epstein-Barr (EBV) DNA and human herpesvirus 8 (HHV-8) DNA asymptomatic salivary shedding in HIV-positive men who have sex with men (MSM). We aimed to 1-analyze frequency and persistence of herpesvirus shedding, 2-correlate herpesvirus positivity and HIV viroimmunological parameters and 3-assess the association between HIV-RNA suppression and herpesvirus replication. Methods Herpesvirus DNA was tested with an in-house real-time PCR in 2 salivary samples obtained at T0 and T1 (24 months after T0). HIV-RNA was evaluated in the 24 months prior to T0 and in the 24 months prior to T1; MSM were classified as successfully suppressed patients (SSPs), viremic patients (VPs) and partially suppressed patients (PSPs). EBV DNA load was classified as low viral load (EBV-LVL, value ≤10,000 copies/ml) and as high viral load (EBV-HVL,> 10,000 copies/ml). Mann-Whitney U test tested the difference of the median between groups of patients. Chi-squared test and Fisher’s exact test compared categorical variables according to the frequencies. Kruskal-Wallis test compared continuous data distributions between levels of categorical variables. Results Ninety-two patients (median CD4+ count 575 cells/mm3, median nadir 330 CD4+ cells/mm3) were included: 40 SSPs,33 VPs and 19 PSPs. The more frequently single virus detected was EBV, both at T0 and at T1 (in 67.5 and 70% of SSPs, in 84.8 and 81.8% of VPs and in 68.4 and 73.7% of SPSs) and the most frequently multiple positivity detected was EBV + HHV-8. At T1, the percentage of CMV positivity was higher in VPs than in SSPs (36.4% vs 5%, p

Published
2018
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12. Prevalence, molecular epidemiology and intra-hospital acquisition of Klebsiella pneumoniae strains producing carbapenemases in an Italian teaching hospital from January 2015 to September 2016

Author

Andrea Bartolini, Monica Basso, Elisa Franchin, Nicola Menegotto, Anna Ferrari, Ettore De Canale, Samantha Andreis, Renzo Scaggiante, Stefania Stefani, Giorgio Palù, and Saverio Giuseppe Parisi

Subjects
carbapenemases, Klebsiella pneumoniae, colistin, longitudinal survey, multilocus sequence typing, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: We described Klebsiella pneumoniae producing carbapenemase (CPKP) spread from 01/01/2015 to 13/09/16 in a tertiary level hospital. Methods: The first positive surveillance rectal swab (SRS) or clinical sample (CS) collected in the medical department (MD), surgical department (SD) and intensive care department (ICD) were included in the study. A validated in-house Real-Time PCR method was used to detect carbapenemases; multilocus sequence typing (MLST) was used for further characterization of the strains. Results: 21535 patients were included: 213 CPKP strains from surveillance rectal swab (SRS) and 98 from clinical samples (CS) were collected. The percentage of CPKP detected in SRS with respect to CS increased in the medical MD from 2015 to 2016 (p = 0.01) and in ICD from 2012 to 2015 (p = 0.0001), while it decreased in SD from 2014 to 2016 (p = 0.003); 68.5% of the positive SRS had a previous negative SRS; CPKP was more frequently identified in CS than in SRS in MD. Twelve strains harboured more than one carbapenemase gene. Many other species harbouring a carbapenemase gene were collected. Conclusions: MDs need more inclusive surveillance criteria. The late detection of positive SRS underlined the risk of colonization during hospitalization.

Published
2017
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13. BNT162b2 SARS-CoV-2 Vaccination Elicits High Titers of Neutralizing Antibodies to Both B.1 and P.1 Variants in Previously Infected and Uninfected Subjects

Author

Ilaria Vicenti, Francesca Gatti, Renzo Scaggiante, Adele Boccuto, Daniela Zago, Monica Basso, Filippo Dragoni, Saverio Giuseppe Parisi, and Maurizio Zazzi

Subjects
SARS-CoV-2 vaccination, neutralizing antibodies, live virus neutralization, B.1 variant, P.1 variant, previously infected and uninfected subjects, Science
Abstract

We aimed to investigate neutralizing antibody titers (NtAbT) to the P.1 and B.1 SARS-CoV-2 variants in a cohort of healthy health care workers (HCW), including 20 previously infected individuals tested at baseline (BLinf, after a median of 298 days from diagnosis) and 21 days after receiving one vaccine dose (D1inf) and 15 uninfected subjects tested 21 days after the second-dose vaccination (D2uninf). All the subjects received BNT162b2 vaccination. D1inf NtAbT increased significantly with respect to BLinf against both B.1 and P.1 variants, with a fold-change significantly higher for P.1. D1inf NtAbT were significantly higher than D2uninf NtAbT, against B.1 and P.1. NtAbT against the two strains were highly correlated. P.1 NtAbT were significantly higher than B.1 NtAbT. This difference was significant for post-vaccination sera in infected and uninfected subjects. A single-dose BNT162b2 vaccination substantially boosted the NtAb response to both variants in the previously infected subjects. NtAb titers to B.1 and P.1 lineages were highly correlated, suggesting substantial cross-neutralization. Higher titers to the P.1 than to the B.1 strain were driven by the post-vaccination titers, highlighting that cross-neutralization can be enhanced by vaccination.

Published
2021
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14. HBcAb Positivity Is a Risk Factor for an Increased Detectability of HIV RNA after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Analysis of a Multicenter Italian Cohort

Author

Vincenzo Malagnino, Elisabetta Teti, Mirko Compagno, Luigi Coppola, Romina Salpini, Valentina Svicher, Monica Basso, Giuliana Battagin, Sandro Panese, Maria Cristina Rossi, Renzo Scaggiante, Daniela Zago, Marco Iannetta, Saverio Giuseppe Parisi, Massimo Andreoni, and Loredana Sarmati

Subjects
anti-HBc, HIV/HBV coinfection, 2DR, 3TC/DTG, dual therapy, Biology (General), QH301-705.5
Abstract

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: p = 0.047; 12th month 34% vs. 27.5%, p = 0.001; 24th month 37% vs. 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs. 11%, p = 0.001; 24 months 37% vs. 13.9%, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that an increase in age of ten years (OR 2.48 (95% CI 1.58–3.89), p < 0.0001) and the presence of HBcAb positivity (OR 2.7 (5% CI 1.05–6.9), p = 0.038) increased the risk of detectability of HIV RNA by nearly three-fold after switching to 2DR-3TC.

Published
2021
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15. Role of pretreatment variables on plasma HIV RNA value at the sixth month of antiretroviral therapy including all first line drugs in HIV naïve patients: A path analysis approach.

Author

Carlo Mengoli, Monica Basso, Samantha Andreis, Renzo Scaggiante, Mario Cruciani, Roberto Ferretto, Sandro Panese, Vinicio Manfrin, Daniela Francisci, Elisabetta Schiaroli, Gaetano Maffongelli, Loredana Sarmati, Massimo Andreoni, Franco Baldelli, Giorgio Palu', and Saverio Giuseppe Parisi

Subjects
Medicine, Science
Abstract

Background and aimsWe investigated the conditioning roles of viral tropism and other variables on plasma HIV RNA levels after 6 months of combination antiretroviral therapy (cART) in an HIV-infected Italian naïve population using regression tree, random forest regression, and path analysis (PA). Patients in this multicenter observational study were treated with all antiviral drugs that are currently recommended as first-line therapies.MethodsAdult patients with chronic HIV infection were enrolled at the beginning of first-line cART (T0). The main variables were age, gender, tropism, "lcd4_0" and "lcd4_6" (log10 CD4+counts at T0 and after 6 months of cART, respectively), and "lrna0" (log10 HIV RNA at T0). Regression tree and random forest analyses were applied. The predictive effect on lrna6 (log10-transformed plasma HIV RNA after 6 months of cART) was also investigated via PA (x4->lcd4_0->lrna0->lrna6) with a treatment selection step included as a dependent (mediator) variable for each third drug and, as predictive covariates, age, female, x4_10, x4_5, lcd4_0, and lrna0. Tropism was assessed in plasma using the Geno2pheno algorithm with 2 false positive rate (FPR) cut-offs: 5% (x4_5) and 10% (x4_10).ResultsThe study included 571 subjects (21% x4_10 and 10.7% x4_5). The only important predictor of lrna6 was lrna0, and a positive indirect effect of bearing X4 virus in plasma was suggested. A significant direct positive effect of protease inhibitors on lrna6 was found (p = 0.022), and a significant negative effect of integrase strand transfer inhibitor (INSTI) was also detected (p = 0.003 for FPR ≤ 5% and p = 0.01 for FPR < 10%). PA predicted mean residual viremias of 40 copies/mL without INSTI and 3 copies/mL with INSTI.ConclusionsPA indicated a possible indirect role of HIV tropism on lrna6 with both FPR < 10% and ≤ 5%. Patients treated with INSTI had a predicted residual viremia of 3 copies/mL.

Published
2019
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16. Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

Author

Bergantini, Laura, Baldassarri, Margherita, D'Alessandro, Miriana, Brunelli, Giulia, Fabbri, Gaia, Zguro, Kristina, Degl'Innocenti, Andrea, Fallerini, Chiara, Bargagli, Elena, Renieri, Alessandra GEN-COVID Multicenter study: Francesca Mari, Sergio, Daga, Ilaria, Meloni, Mirella, Bruttini, Susanna, Croci, Mirjam, Lista, Debora, Maffeo, Elena, Pasquinelli, Viola Bianca Serio, Enrica, Antolini, Simona Letizia Basso, Samantha, Minetto, Rossella, Tita, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca, Ariani, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Arianna, Emiliozzi, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Maria, Lorubbio, Alessandro, Pancrazzi, Massimo, Vaghi, Antonella, D 'Arminio Monforte, Federica Gaia Miraglia, Mario, U Mondelli, Stefania, Mantovani, Raffaele, Bruno, Marco, Vecchia, Marcello, Maffezzoni, Enrico, Martinelli, Massimo, Girardis, Stefano, Busani, Sophie, Venturelli, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Carlo, Pallotto, Saverio Giuseppe Parisi, Monica, Basso, Sandro, Panese, Stefano, Baratti, Pier Giorgio Scotton, Francesca, Andretta, Mario, Giobbia, Renzo, Scaggiante, Francesca, Gatti, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo Della Monica, Carmelo, Piscopo, Mario, Capasso, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Giuseppe, Merla, Gabriella Maria Squeo, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Serafina, Valente, Alex Di Florio, Marco, Mandalà, Alessia, Giorli, Lorenzo, Salerni, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Gianluca, Lacerenza, Cristina, Mussini, Luisa, Tavecchia, Lia, Crotti, Gianfranco, Parati, Roberto, Menè, Maurizio, Sanarico, Marco, Gori, Francesco, Raimondi, Alessandra, Stella, Filippo, Biscarini, Tiziana, Bachetti, Maria Teresa La Rovere, Maurizio, Bussotti, Serena, Ludovisi, Katia, Capitani, Simona, Dei, Sabrina, Ravaglia, Annarita, Giliberti, Giulia, Gori, Rosangela, Artuso, Elena, Andreucci, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Sauro, Luchi, Giovanna, Morelli, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Micheli, Giulia, Marco, Falcone, Donato, Urso, Giusy, Tiseo, Tommaso, Matucci, Grassi, Davide, Ferri, Claudio, Marinangeli, Franco, Brancati, Francesco, Antonella, Vincenti, Valentina, Borgo, Lombardi, Stefania, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Alessio, Bellucci, Marta, Colaneri, Patrizia, Casprini, Cristoforo, Pomara, Massimiliano, Esposito, Roberto, Leoncini, Michele, Cirianni, Lucrezia, Galasso, Marco Antonio Bellini, Chiara, Gabbi, Nicola, Picchiotti, and Simone, Furini

Subjects
COVID-19, Long COVID, Pulmonary fibrosis, RTEL1
Published
2023

17. Daclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin

Author

Saverio G. Parisi, Arianna Loregian, Samantha Andreis, Giulio Nannetti, Silvia Cavinato, Monica Basso, Renzo Scaggiante, Federico Dal Bello, Lorenzo Messa, Anna Maria Cattelan, and Giorgio Palù

Subjects
Daclatasvir, HIV–HCV patients, Therapeutic drug monitoring, Virological failure, Population-based sequencing, Mutation, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Effective treatment with direct-acting antiviral drugs against hepatitis C virus (HCV) is a medical need in cirrhotic HIV–HCV co-infected patients. Methods: This study investigated the plasma levels of daclatasvir (DCV) and ribavirin (RBV) in HIV–HCV co-infected subjects treated with DCV, sofosbuvir, and RBV. Drug concentrations were quantified using validated high-performance liquid chromatography methods with ultraviolet detection. The HCV non-structural protein 5A and non-structural protein 5B coding regions were analyzed by population-based sequencing. Results: DCV was dosed at week 4 and at week 8 of treatment, and RBV at week 8. One patient had the lowest DCV level, corresponding to 32.7% of the overall median value of the other patients at week 4 and about 40% at week 8. The Y93H variant was detected in this subject at weeks 8, 16, and 20 of treatment, but not before treatment or at day 2, and the patient experienced virological failure. Another subject with the Y93H variant at baseline and appropriate DCV levels had HCV RNA

Published
2016
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18. Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Author

Zguro, Kristina, Baldassarri, Margherita, Fava, Francesca, Beligni, Giada, Daga, Sergio, Leoncini, Roberto, Galasso, Lucrezia, Cirianni, Michele, Rusconi, Stefano, Siano, Matteo, Francisci, Daniela, Schiaroli, Elisabetta, Luchi, Sauro, Morelli, Giovanna, Martinelli, Enrico, Girardis, Massimo, Busani, Stefano, Parisi, Saverio Giuseppe, Panese, Sandro, Piscopo, Carmelo, Capasso, Mario, Tacconi, Danilo, Spertilli Raffaelli, Chiara, Giliberti, Annarita, Gori, Giulia, Katsikis, Peter D, Lorubbio, Maria, Calzoni, Paola, Ognibene, Agostino, Bocchia, Monica, Tozzi, Monica, Bucalossi, Alessandro, Marotta, Giuseppe, Furini, Simone, Gen-Covid Multicenter Study, Null, Renieri, Alessandra, Fallerini, Chiara, GEN-COVID Multicenter Study, Mari, Francesca, Bruttini, Mirella, Meloni, Ilaria, Croci, Susanna, Gabriella, Doddato, Serio, VIOLA BIANCA, Mirjam, Lista, Maffeo, Debora, Pasquinelli, Elena, Ludovica, Mercuri, Brunelli, Giulia, Rossella, Tita, Maria Antonietta Mencarelli, LO RIZZO, Caterina, Pinto, ANNA MARIA, Ariani, Francesca, Montagnani, Francesca, Tumbarello, Mario, Ilaria, Rancan, Massimiliano, Fabbiani, Bargagli, Elena, Bergantini, Laura, D'Alessandro, Miriana, Cameli, Paolo, Bennett, David, Federico, Anedda, Simona, Marcantonio, Scolletta, Sabino, Franchi, Federico, Mazzei, MARIA ANTONIETTA, Susanna, Guerrini, Edoardo, Conticini, Cantarini, Luca, Frediani, Bruno, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Alessandro, Pancrazzi, Massimo, Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Mondelli, Mario U., Stefania, Mantovani, Raffaele, Bruno, Marco, Vecchia, Marcello, Maffezzoni, Sophie, Venturelli, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Arianna, Gabrieli, Agostino, Riva, Andrea, Tommasi, Pier Giorgio Scotton, Francesca, Andretta, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo della Monica, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Giuseppe, Merla, Gabriella Maria Squeo, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Valente, Serafina, Alex Di Florio, Mandala', Marco, Giorli, Alessia, Salerni, Lorenzo, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Gianluca, Lacerenza, Cristina, Mussini, Luisa, Tavecchia, Lia, Crotti, Gianfranco, Parati, Roberto, Menè, Maurizio, Sanarico, Gori, Marco, Nicola, Picchiotti, Francesco, Raimondi, Alessandra, Stella, Filippo, Biscarini, Tiziana, Bachetti, Maria Teresa La Rovere, Maurizio, Bussotti, Serena, Ludovisi, Katia, Capitani, Chiara, Gabbi, Simona, Dei, Sabrina, Ravaglia, Rosangela, Artuso, Elena, Andreucci, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Giulia, Micheli, Marco, Falcone, Giusy, Tiseo, Chiara, Barbieri, Tommaso, Matucci, Davide, Grassi, Claudio, Ferri, Franco, Marinangeli, Francesco, Brancati, Antonella, Vincenti, Valentina, Borgo, Stefania, Lombardi, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Alessio, Bellucci, Marta, Colaneri, Patrizia, Casprini, Cristoforo, Pomara, Massimiliano, Esposito, Marco Antonio Bellini, Zguro, Kristina, Baldassarri, Margherita, Fava, Francesca, Beligni, Giada, Daga, Sergio, Leoncini, Roberto, Galasso, Lucrezia, Cirianni, Michele, Rusconi, Stefano, Siano, Matteo, Francisci, Daniela, Schiaroli, Elisabetta, Luchi, Sauro, Morelli, Giovanna, Martinelli, Enrico, Girardis, Massimo, Busani, Stefano, Parisi, Saverio Giuseppe, Panese, Sandro, Piscopo, Carmelo, Capasso, Mario, Tacconi, Danilo, Spertilli Raffaelli, Chiara, Giliberti, Annarita, Gori, Giulia, Katsikis, Peter D, Lorubbio, Maria, Calzoni, Paola, Ognibene, Agostino, Bocchia, Monica, Tozzi, Monica, Bucalossi, Alessandro, Marotta, Giuseppe, Furini, Simone, Gen-Covid Multicenter Study, Null, Renieri, Alessandra, Fallerini, Chiara, Gen-Covid Multicenter Study, null, and Immunology

Subjects
Thrombotic Thrombocytopenic, Purpura, Thrombotic Thrombocytopenic, SARS-CoV-2, COVID-19, ADAMTS13, thromboembolism, add-on therapy, ADAMTS13 Protein, ADAM Proteins, Infectious Diseases, SDG 3 - Good Health and Well-being, Virology, von Willebrand Factor, Humans, Purpura
Abstract

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF–platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.

Published
2022

19. An explainable model of host genetic interactions linked to COVID-19 severity

Author

Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, Ludovisi, S, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi Francesco, Francesca Mari, Sergio Daga, Elisa Benetti, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Ilaria Meloni, Elisa Frullanti, Gabriella Doddato, Mirjam Lista, Giada Beligni, Floriana Valentino, Kristina Zguro, Rossella Tita, Annarita Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Laura Di Sarno, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Barbara Rossetti, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Raffaele Bruno, Marco Vecchia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Andrea Tommasi, Umberto Zuccon, Lucia Vietri, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Stefano Baratti, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Oreste De Vivo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Lia Crotti, Gianfranco Parati, Maurizio Sanarico, Filippo Biscarini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Katia Capitani, Simona Dei, Sabrina Ravaglia, Rosangela Artuso, Elena Andreucci, Giulia Gori, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Francesco Vladimiro Segala, Francesco Menichetti, Marco Falcone, Giusy Tiseo, Chiara Barbieri, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Roberto Menè, Marta Colaneri, Patrizia Casprini, Giuseppe Merla, Gabriella Maria Squeo, Marcello Maffezzoni, Stefania Mantovani, Mario U. Mondelli &, Serena Ludovisi, Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, Ludovisi, S, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi Francesco, Francesca Mari, Sergio Daga, Elisa Benetti, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Ilaria Meloni, Elisa Frullanti, Gabriella Doddato, Mirjam Lista, Giada Beligni, Floriana Valentino, Kristina Zguro, Rossella Tita, Annarita Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Laura Di Sarno, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Barbara Rossetti, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Raffaele Bruno, Marco Vecchia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Andrea Tommasi, Umberto Zuccon, Lucia Vietri, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Stefano Baratti, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Oreste De Vivo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Lia Crotti, Gianfranco Parati, Maurizio Sanarico, Filippo Biscarini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Katia Capitani, Simona Dei, Sabrina Ravaglia, Rosangela Artuso, Elena Andreucci, Giulia Gori, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Francesco Vladimiro Segala, Francesco Menichetti, Marco Falcone, Giusy Tiseo, Chiara Barbieri, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Roberto Menè, Marta Colaneri, Patrizia Casprini, Giuseppe Merla, Gabriella Maria Squeo, Marcello Maffezzoni, Stefania Mantovani, Mario U. Mondelli &, and Serena Ludovisi

Abstract

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, supporting their link with COVID-19 severity outcome.

Published
2022

20. The second dose of the BNT162b2 mRNA vaccine does not boost SARS-CoV-2 neutralizing antibody response in previously infected subjects

Author

Ilaria Vicenti, Adele Boccuto, Renzo Scaggiante, Daniela Zago, Saverio Giuseppe Parisi, Maurizio Zazzi, Filippo Dragoni, Francesca Gatti, and Monica Basso

Subjects
Microbiology (medical), Vaccines, Synthetic, 2019-20 coronavirus outbreak, Messenger RNA, biology, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, General Medicine, Antibodies, Neutralizing, Virology, Infectious Diseases, Correspondence, biology.protein, Humans, Medicine, mRNA Vaccines, business, Neutralizing antibody, BNT162 Vaccine
Published
2021
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21. Single-dose BNT162b2 mRNA COVID-19 vaccine significantly boosts neutralizing antibody response in health care workers recovering from asymptomatic or mild natural SARS-CoV-2 infection

Author

Francesca Gatti, Adele Boccuto, Renzo Scaggiante, Maurizio Zazzi, Monica Basso, Ilaria Vicenti, Saverio Giuseppe Parisi, Filippo Dragoni, and Daniela Zago

Subjects
0301 basic medicine, Microbiology (medical), COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Short Communication, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health Personnel, 030106 microbiology, Messenger, Neutralizing antibody response, Infectious and parasitic diseases, RC109-216, BNT162b2 mRNA COVID-19 vaccine, Health care workers, Asymptomatic, Antibodies, Antibodies, Neutralizing, BNT162 Vaccine, Humans, RNA, Messenger, COVID-19, SARS-CoV-2, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, medicine, 030212 general & internal medicine, Neutralizing antibody, Neutralizing, Live virus, biology, business.industry, General Medicine, Vaccination, Infectious Diseases, Humoral immunity, Immunology, biology.protein, RNA, medicine.symptom, business
Abstract

OBJECTIVES: To measure SARS-CoV-2 neutralizing antibody (NtAb) titres in previously infected or uninfected health care workers who received one or two doses of BNT162b2 mRNA COVID-19 vaccine. METHODS: NtAbs were titrated as dose-inhibiting 50% virus replication (ID50) by live virus microneutralization. We evaluated 41 health care workers recovering from mild or asymptomatic infection at first vaccination dose (T1_inf) and 21 days later (T2_inf). Sixteen uninfected health care workers were evaluated 20 days after first dose (T2_uninf) and 20 days after second vaccine dose (T3_uninf). RESULTS: At T2_inf, but not at T1_inf, there was a significant correlation between days from diagnosis (median 313, interquartile range 285-322) and NtAb levels (P = 0.011). NtAb titres increased at T2_inf with respect to T1_inf (1544 (732-2232) vs 26 (10-88), P < 0.001). Similarly, there was a significant increase in NtAb titres at T3_uninf compared with T2_uninf (183 (111-301) vs 5 (5-15), P < 0001). However, NtAb levels at T2_inf were significantly higher than those at T2_uninf and T3_uninf (P < 0.0001 for both analyses). CONCLUSIONS: A single vaccination in people with mild or asymptomatic previous infection further boosts SARS-CoV-2 humoral immunity to levels higher than those obtained by complete two-vaccination in uninfected subjects.

Published
2021

22. An explainable model of host genetic interactions linked to COVID-19 severity

Author

Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi, Francesco GEN-COVID Multicenter Study: Francesca Mari, Sergio, Daga, Elisa, Benetti, Mirella, Bruttini, Maria, Palmieri, Susanna, Croci, Sara, Amitrano, Ilaria, Meloni, Elisa, Frullanti, Gabriella, Doddato, Mirjam, Lista, Giada, Beligni, Floriana, Valentino, Kristina, Zguro, Rossella, Tita, Annarita, Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca, Ariani, Laura Di Sarno, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Barbara, Rossetti, Laura, Bergantini, Miriana, D'Alessandro, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Alessandro, Pancrazzi, Maria, Lorubbio, Massimo, Vaghi, Antonella D'Arminio Monforte, Federica Gaia Miraglia, Raffaele, Bruno, Marco, Vecchia, Massimo, Girardis, Sophie, Venturelli, Stefano, Busani, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Francesco, Paciosi, Andrea, Tommasi, Umberto, Zuccon, Lucia, Vietri, Pier Giorgio Scotton, Francesca, Andretta, Sandro, Panese, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Saverio Giuseppe Parisi, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo Della Monica, Carmelo, Piscopo, Mario, Capasso, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Serafina, Valente, Oreste De Vivo, Elena, Bargagli, Marco, Mandalà, Alessia, Giorli, Lorenzo, Salerni, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Gianluca, Lacerenza, Domenico, A Coviello, Cristina, Mussini, Enrico, Martinelli, Luisa, Tavecchia, Mary Ann Belli, Lia, Crotti, Gianfranco, Parati, Maurizio, Sanarico, Filippo, Biscarini, Alessandra, Stella, Marco, Rizzi, Franco, Maggiolo, Diego, Ripamonti, Claudia, Suardi, Tiziana, Bachetti, Maria Teresa La Rovere, Simona, Sarzi-Braga, Maurizio, Bussotti, Katia, Capitani, Simona, Dei, Sabrina, Ravaglia, Rosangela, Artuso, Elena, Andreucci, Giulia, Gori, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Sauro, Luchi, Giovanna, Morelli, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Francesco Vladimiro Segala, Francesco, Menichetti, Marco, Falcone, Giusy, Tiseo, Chiara, Barbieri, Tommaso, Matucci, Grassi, Davide, Ferri, Claudio, Marinangeli, Franco, Brancati, Francesco, Antonella, Vincenti, Valentina, Borgo, Lombardi, Stefania, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Roberto, Menè, Marta, Colaneri, Patrizia, Casprini, Giuseppe, Merla, Gabriella Maria Squeo, Marcello, Maffezzoni, Stefania, Mantovani, Mario, U Mondelli, Serena, Ludovisi, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, nbsp, Multicenter Study, GEN-COVID, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi, Francesco, Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, and Ludovisi, S

Subjects
Genetics, Coronavirus disease 2019 (COVID-19), Host (biology), COVID-19, Medicine (miscellaneous), Settore BIO/11 - Biologia Molecolare, Biology, Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA, Whole Exome Sequencing, General Biochemistry, Genetics and Molecular Biology, machine learning, Phenotype, Exome Sequencing, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study, General Agricultural and Biological Sciences, COVID, Human
Abstract

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with training of multiple supervised classifiers, to predict severity on the basis of screened features. Feature importance analysis from tree-based models allowed to identify a handful of 16 variants with highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with good accuracy (ACC=81.88%; ROC_AUC=96%; MCC=61.55%). Principal Component Analysis (PCA) and clustering of patients on important variants orthogonally identified two groups of individuals with a higher fraction of severe cases. Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response, such as JAK-STAT, Cytokine, Interleukin, and C-type lectin receptor signaling. It also identified additional processes cross-talking with immune pathways, such as GPCR signalling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, confirming their link with COVID-19 severity outcome. Taken together, our analysis suggests that curated genetic information can be effectively integrated along with other patient clinical covariates to forecast COVID-19 disease severity and dissect the underlying host genetic mechanisms for personalized medicine treatments.

Published
2022
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23. Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

Author

Fallerini, Chiara, Picchiotti, Nicola, Baldassarri, Margherita, Zguro, Kristina, Daga, Sergio, Fava, Francesca, Benetti, Elisa, Amitrano, Sara, Bruttini, Mirella, Palmieri, Maria, Croci, Susanna, Lista, Mirjam, Beligni, Giada, Valentino, Floriana, Meloni, Ilaria, Tanfoni, Marco, Minnai, Francesca, Colombo, Francesca, Cabri, Enrico, Fratelli, Maddalena, Gabbi, Chiara, Mantovani, Stefania, Frullanti, Elisa, Gori, Marco, Crawley, Francis P, Butler-Laporte, Guillaume, Richards, Brent, Zeberg, Hugo, Lipcsey, Miklos, Hultström, Michael, Ludwig, Kerstin U, Schulte, Eva C, Pairo-Castineira, Erola, Baillie, John Kenneth, Schmidt, Axel, Frithiof, Robert, Mari, Francesca, Renieri, Alessandra, Furini, Simone Simone Furini, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Barbara, Rossetti, Laura, Bergantini, Miriana, D'Alessandro, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Maurizio, Spagnesi, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Alessandro, Pancrazzi, Maria, Lorubbio, Massimo, Vaghi, Antonella, D 'Arminio Monforte, Federica Gaia Miraglia, Mario, U Mondelli, Massimo, Girardis, Sophie, Venturelli, Stefano, Busani, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Francesco, Paciosi, Andrea, Tommasi, Pier Giorgio Scotton, Francesca, Andretta, Sandro, Panese, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Saverio 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L, Omar, Z, Perkins, E, Davies, K, Tetla, D, Shelley, B, Irvine, V, Williams, S, Williams, P, Goodsell, J, Tutton, R, Bough, L, Winter-Goodwin, B, Kitson, R, Pinnell, J, Wilson, A, Nortcliffe, T, Wood, T, Home, M, Holdroyd, K, Robinson, M, Shaw, R, Greig, J, Brady, M, Haigh, A, Matupe, L, Usher, M, Mellor, S, Dale, S, Gledhill, L, Shaw, L, Turner, G, Kelly, D, Anwar, B, Riley, H, Sturgeon, H, Ali, A, Thomis, L, Melia, D, Dance, A, Hanson, K, Humphreys, S, Frost, I, Gopal, V, Godden, J, Holden, A, Swann, S, Smith, T, Clapham, M, Poultney, U, Harper, R, Rice, P, Reece-Anthony, R, Gurung, B, Moultrie, S, Odam, M, Mayer, A, Bellini, A, Pickard, A, Bryant, J, Roe, N, Sowter, J, Lang, K, Taylor, J, Barry, P, Hobrok, M, Tench, H, Wolf-Roberts, R, Mcguinness, H, Loosley, R, Hawcutt, D, Rad, L, O'Malley, L, Saunderson, P, Seddon, G, Anderson, T, Rogers, N, Ruddy, J, Harkins, M, Beith, C, Mcalpine, A, Ferguson, L, Grant, P, Macfadyen, S, Mclaughlin, M, Baird, T, Rundell, S, Welsh, B, Hamill, R, Fisher, F, Gregory, J, Axel, Schmidt, Kerstin, U Ludwig, Selina, Rolker, Markus, M Nöthen, Julia, Fazaal, Verena, Keitel, Björn, Jensen, Torsten, Feldt, Lisa, Knopp, Julia, Schröder, Carlo, Maj, Fabian, Brand, Marc, M Berger, Thorsten, Brenner, Anke, Hinney, Oliver, Witzke, Robert, Bals, Christian, Herr, Nicole, Ludwig, Jörn, Walter, Jochen, Schneider, Johanna, Erber, Christoph, D Spinner, Clemens, M Wendtner, Christof, Winter, Ulrike, Protzer, Nicolas, Casadei, Stephan, Ossowski, Olaf, H Riess, Eva, C Schulte, J Brent Richards, Guillaume, Butler-Laporte, Mirosław, Kwasniewski, Urszula, Korotko, Karolina, Chwialkowska, Magdalena, Niemira, Jerzy, Jaroszewicz, Barbara, Sobala-Szczygiel, Beata, Puzanowska, Anna, Parfieniuk-Kowerda, Diana, Martonik, Anna, Moniuszko-Malinowska, Sławomir, Pancewicz, Dorota, Zarębska-Michaluk, Krzysztof, Simon, Monika, Pazgan-Simon, Iwona, Mozer-Lisewska, Maciej, Bura, Agnieszka, Adamek, Krzysztof Tomasiewicz Małgorzata Pawłowska, Anna, Piekarska, Aleksandra, Berkan-Kawinska, Andrzej, Horban, Justyna, Kowalska, Regina, Podlasin, Piotr, Wasilewski, Arsalin, Azzadin, Miroslaw, Czuczwar, Slawomir, Czaban, Paweł, Olszewski, Jacek, Bogocz, Magdalena, Ochab, Anna, Kruk, Sandra, Uszok, Agnieszka, Bielska, Anna, Szałkowska, Justyna, Raczkowska, Gabriela, Sokołowska, Joanna, Chorostowska-Wynimko, Aleksandra, Jezela-Stanek, Adriana, Roży, Urszula, Lechowicz, Urszula, Polowianiuk, Kamil, Grubczak, Aleksandra, Starosz, Andrzej, Eljaszewicz, Wiktoria, Izdebska, Adam, Krętowski, Robert, Flisiak, Marcin Moniuszko Malak Abedalthagafi Manal Alaamery, Salam, Massadeh, Mohamed, Fawzy, Hadeel, Albardis, Nora, Aljawini, Moneera, Alsuwailm, Faisal, Almalki, Serghei, Mangul, Junghyun, Jung, Hamdi, Mbarek, Chadi, Saad, Yaser, Al-Sarraj, Wadha, Al-Muftah, Radja, Badji, Asma Al Thani, Said, I Ismail, HGI, WES/WGS Working Group Within the, Consortium, GenOMICC, Study, GEN-COVID Multicenter, Renieri, Alessandra [0000-0002-0846-9220], Apollo - University of Cambridge Repository, NIHR, Fallerini, C, Picchiotti, N, Baldassarri, M, Zguro, K, Daga, S, Fava, F, Benetti, E, Amitrano, S, Bruttini, M, Palmieri, M, Croci, S, Lista, M, Beligni, G, Valentino, F, Meloni, I, Tanfoni, M, Minnai, F, Colombo, F, Cabri, E, Fratelli, M, Gabbi, C, Mantovani, S, Frullanti, E, Gori, M, Crawley, F, Butler-Laporte, G, Richards, B, Zeberg, H, Lipcsey, M, Hultström, M, Ludwig, K, Schulte, E, Pairo-Castineira, E, Baillie, J, Schmidt, A, Frithiof, R, Mari, F, Renieri, A, Furini, S, and Crotti, L

Subjects
Male, Medicin och hälsovetenskap, Linkage disequilibrium, Medizin, severity, Genome-wide association study, Disease, WES/WGS Working Group Within the HGI, Logistic regression, Severity of Illness Index, Medical and Health Sciences, Whole Exome Sequencing, Cohort Studies, 0302 clinical medicine, Lasso (statistics), GEN-COVID Multicenter Study, Germany, 80 and over, Genetics (clinical), Exome sequencing, Original Investigation, Genetics & Heredity, Aged, 80 and over, 0303 health sciences, Adult, Aged, COVID-19, Female, Humans, Italy, Middle Aged, Polymorphism, Single Nucleotide, Quebec, SARS-CoV-2, Sweden, United Kingdom, Genetic Predisposition to Disease, Phenotype, Single Nucleotide, covid-19, 1104 Complementary and Alternative Medicine, GenOMICC Consortium, Human, coding variants, Computational biology, Biology, 03 medical and health sciences, Exome Sequencing, Genetics, Polymorphism, Gene, 030304 developmental biology, 0604 Genetics, 1114 Paediatrics and Reproductive Medicine, Cohort Studie, 030217 neurology & neurosurgery, Coding (social sciences)
Abstract

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. Supplementary Information The online version contains supplementary material available at 10.1007/s00439-021-02397-7.

Published
2021
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24. BNT162b2 SARS-CoV-2 Vaccination Elicits High Titers of Neutralizing Antibodies to Both B.1 and P.1 Variants in Previously Infected and Uninfected Subjects

Author

Filippo Dragoni, Daniela Zago, Renzo Scaggiante, Ilaria Vicenti, Adele Boccuto, Francesca Gatti, Monica Basso, Saverio Giuseppe Parisi, and Maurizio Zazzi

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Science, health care workers, General Biochemistry, Genetics and Molecular Biology, previously infected and uninfected subjects, Medicine, neutralizing antibodies, Neutralizing antibody, Ecology, Evolution, Behavior and Systematics, biology, live virus neutralization, business.industry, Brief Report, B.1 variant, P.1 variant, SARS-CoV-2 vaccination, Paleontology, Vaccination, Health care workers, Live virus neutralization, Neutralizing antibodies, Previously infected and uninfected subjects, Titer, Space and Planetary Science, Immunology, Cohort, biology.protein, Antibody, business
Abstract

We aimed to investigate neutralizing antibody titers (NtAbT) to the P.1 and B.1 SARS-CoV-2 variants in a cohort of healthy health care workers (HCW), including 20 previously infected individuals tested at baseline (BLinf, after a median of 298 days from diagnosis) and 21 days after receiving one vaccine dose (D1inf) and 15 uninfected subjects tested 21 days after the second-dose vaccination (D2uninf). All the subjects received BNT162b2 vaccination. D1inf NtAbT increased significantly with respect to BLinf against both B.1 and P.1 variants, with a fold-change significantly higher for P.1. D1inf NtAbT were significantly higher than D2uninf NtAbT, against B.1 and P.1. NtAbT against the two strains were highly correlated. P.1 NtAbT were significantly higher than B.1 NtAbT. This difference was significant for post-vaccination sera in infected and uninfected subjects. A single-dose BNT162b2 vaccination substantially boosted the NtAb response to both variants in the previously infected subjects. NtAb titers to B.1 and P.1 lineages were highly correlated, suggesting substantial cross-neutralization. Higher titers to the P.1 than to the B.1 strain were driven by the post-vaccination titers, highlighting that cross-neutralization can be enhanced by vaccination.

Published
2021

25. HIV tropism switch in archived DNA of HIV-HCV subjects successfully treated with direct-acting antivirals for HCV infection

Author

Silvia Cavinato, Loredana Sarmati, Renzo Scaggiante, Irene Pozzetto, Monica Basso, Beatrice Parisatto, Saverio Giuseppe Parisi, Anna Maria Cattelan, Daniela Zago, Giuliana Battagin, and Camilla Stagni

Subjects
0301 basic medicine, Male, Science, Mononuclear, 030106 microbiology, Viremia, Diseases, HIV Infections, Disease, Pathogenesis, Hepacivirus, DIRECT ACTING ANTIVIRALS, Peripheral blood mononuclear cell, Antiviral Agents, Virus, Article, 03 medical and health sciences, chemistry.chemical_compound, Medical research, Leukocytes, HIV tropism, medicine, Humans, Viral, Longitudinal Studies, Tropism, Multidisciplinary, business.industry, Coinfection, virus diseases, DNA, Middle Aged, medicine.disease, Virology, Hepatitis C, Settore MED/17, Viral Tropism, 030104 developmental biology, chemistry, DNA, Viral, Female, HIV-1, Leukocytes, Mononuclear, Medicine, business
Abstract

We described short-term HIV tropism changes occurring in peripheral blood mononuclear cells and the correlations with HIV DNA value in HIV-HCV co-infected patients cured for HCV disease and with undetectable HIV viremia or residual viremia (RV). Plasma HIV RNA, cellular HIV DNA and tropism were evaluated pre-HCV treatment (baseline, BL) and at 12(T1) and 24(T2) weeks after HCV treatment start. V3 sequences were interpreted using Geno2pheno and classified as R5 only if all three sequences had an FPR ≥ 10% and as X4 when at least one replicate sequence had an FPR

Published
2021

26. SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Author

Matteo D’Antonio, Jennifer P. Nguyen, Timothy D. Arthur, Hiroko Matsui, Agnieszka D’Antonio-Chronowska, Kelly A. Frazer, Benjamin M. Neale, Mark Daly, Andrea Ganna, Christine Stevens, Gita A. Pathak, Shea J. Andrews, Masahiro Kanai, Mattia Cordioli, Juha Karjalainen, Renato Polimanti, Matti Pirinen, Nadia Harerimana, Kumar Veerapen, Brooke Wolford, Huy Nguyen, Matthew Solomonson, Rachel G. Liao, Karolina Chwialkowska, Amy Trankiem, Mary K. Balaconis, Caroline Hayward, Anne Richmond, Archie Campbell, Marcela Morris, Chloe Fawns-Ritchie, Joseph T. Glessner, Douglas M. Shaw, Xiao Chang, Hannah Polikowski, Petty E. Lauren, Hung-Hsin Chen, Zhu Wanying, Hakon Hakonarson, David J. Porteous, Jennifer Below, Kari North, Joseph B. McCormick, Paul R.H.J. Timmers, James F. Wilson, Albert Tenesa, Kenton D’Mellow, Shona M. Kerr, Mari E.K. Niemi, Lindokuhle Nkambul, Kathrin Aprile von Hohenstaufen, Ali Sobh, Madonna M. Eltoukhy, Amr M. Yassen, Mohamed A.F. Hegazy, Kamal Okasha, Mohammed A. Eid, Hanteera S. Moahmed, Doaa Shahin, Yasser M. El-Sherbiny, Tamer A. Elhadidy, Mohamed S. Abd Elghafar, Jehan J. El-Jawhari, Attia A.S. Mohamed, Marwa H. Elnagdy, Amr Samir, Mahmoud Abdel-Aziz, Walid T. Khafaga, Walaa M. El-Lawaty, Mohamed S. Torky, Mohamed R. El-shanshory, Chiara Batini, Paul H. Lee, Nick Shrine, Alexander T. Williams, Martin D. Tobin, Anna L. Guyatt, Catherine John, Richard J. Packer, Altaf Ali, Robert C. Free, Xueyang Wang, Louise V. Wain, Edward J. Hollox, Laura D. Venn, Catherine E. Bee, Emma L. Adams, Ahmadreza Niavarani, Bahareh Sharififard, Rasoul Aliannejad, Ali Amirsavadkouhi, Zeinab Naderpour, Hengameh Ansari Tadi, Afshar Etemadi Aleagha, Saeideh Ahmadi, Seyed Behrooz Mohseni Moghaddam, Alireza Adamsara, Morteza Saeedi, Hamed Abdollahi, Abdolmajid Hosseini, Pajaree Chariyavilaskul, Monpat Chamnanphon, Thitima B. Suttichet, Vorasuk Shotelersuk, Monnat Pongpanich, Chureerat Phokaew, Wanna Chetruengchai, Watsamon Jantarabenjakul, Opass Putchareon, Pattama Torvorapanit, Thanyawee Puthanakit, Pintip Suchartlikitwong, Nattiya Hirankarn, Voraphoj Nilaratanakul, Pimpayao Sodsai, Ben M. Brumpton, Kristian Hveem, Cristen Willer, Wei Zhou, Tormod Rogne, Erik Solligard, Bjørn Olav Åsvold, Malak Abedalthagafi, Manal Alaamery, Saleh Alqahtani, Dona Baraka, Fawz Al Harthi, Ebtehal Alsolm, Leen Abu Safieh, Albandary M. Alowayn, Fatimah Alqubaishi, Amal Al Mutairi, Serghei Mangul, Abdulraheem Alshareef, Mona Sawaji, Mansour Almutairi, Nora Aljawini, Nour Albesher, Yaseen M. Arabi, Ebrahim S. Mahmoud, Amin K. Khattab, Roaa T. Halawani, Ziab Z. Alahmadey, Jehad K. Albakri, Walaa A. Felemban, Bandar A. Suliman, Rana Hasanato, Laila Al-Awdah, Jahad Alghamdi, Deema AlZahrani, Sameera AlJohani, Hani Al-Afghani, May Alrashed, Nouf AlDhawi, Hadeel AlBardis, Sarah Alkwai, Moneera Alswailm, Faisal Almalki, Maha Albeladi, Iman Almohammed, Eman Barhoush, Anoud Albader, Salam Massadeh, Abdulaziz AlMalik, Sara Alotaibi, Bader Alghamdi, Junghyun Jung, Mohammad S. Fawzy, Yunsung Lee, Per Magnus, Lill-Iren S. Trogstad, Øyvind Helgeland, Jennifer R. Harris, Massimo Mangino, Tim D. Spector, Duncan Emma, Sandra P. Smieszek, Bartlomiej P. Przychodzen, Christos Polymeropoulos, Vasilios Polymeropoulos, Mihael H. Polymeropoulos, Israel Fernandez-Cadenas, Jordi Perez-Tur, Laia Llucià-Carol, Natalia Cullell, Elena Muiño, Jara Cárcel-Márquez, Marta L. DeDiego, Lara Lloret Iglesias, Anna M. Planas, Alex Soriano, Veronica Rico, Daiana Agüero, Josep L. Bedini, Francisco Lozano, Carlos Domingo, Veronica Robles, Francisca Ruiz-Jaén, Leonardo Márquez, Juan Gomez, Eliecer Coto, Guillermo M. Albaiceta, Marta García-Clemente, David Dalmau, Maria J. Arranz, Beatriz Dietl, Alex Serra-Llovich, Pere Soler, Roger Colobrán, Andrea Martín-Nalda, Alba Parra Martínez, David Bernardo, Silvia Rojo, Aida Fiz-López, Elisa Arribas, Paloma de la Cal-Sabater, Tomás Segura, Esther González-Villa, Gemma Serrano-Heras, Joan Martí-Fàbregas, Elena Jiménez-Xarrié, Alicia de Felipe Mimbrera, Jaime Masjuan, Sebastian García-Madrona, Anna Domínguez-Mayoral, Joan Montaner Villalonga, Paloma Menéndez-Valladares, Daniel I. Chasman, Julie E. Buring, Paul M. Ridker, Giulianini Franco, Howard D. Sesso, JoAnn E. Manson, Joseph R. Glessner, Carolina Medina-Gomez, Andre G. Uitterlinden, M. Arfan Ikram, Kati Kristiansson, Sami Koskelainen, Markus Perola, Kati Donner, Katja Kivinen, Aarno Palotie, Samuli Ripatti, Sanni Ruotsalainen, Mari Kaunisto, null FinnGen, Tomoko Nakanishi, Guillaume Butler-Laporte, Vincenzo Forgetta, David R. Morrison, Biswarup Ghosh, Laetitia Laurent, Alexandre Belisle, Danielle Henry, Tala Abdullah, Olumide Adeleye, Noor Mamlouk, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk Branka Vulesevic, Meriem Bouab, Charlotte Guzman, Louis Petitjean, Chris Tselios, Xiaoqing Xue, Erwin Schurr, Jonathan Afilalo, Marc Afilalo, Maureen Oliveira, Bluma Brenner, Pierre Lepage, Jiannis Ragoussis, Daniel Auld, Nathalie Brassard, Madeleine Durand, Michaël Chassé, Daniel E. Kaufmann, G. Mark Lathrop, Vincent Mooser, J. Brent Richards, Rui Li, Darin Adra, Souad Rahmouni, Michel Georges, Michel Moutschen, Benoit Misset, Gilles Darcis, Julien Guiot, Julien Guntz, Samira Azarzar, Stéphanie Gofflot, Yves Beguin, Sabine Claassen, Olivier Malaise, Pascale Huynen, Christelle Meuris, Marie Thys, Jessica Jacques, Philippe Léonard, Frederic Frippiat, Jean-Baptiste Giot, Anne-Sophie Sauvage, Christian Von Frenckell, Yasmine Belhaj, Bernard Lambermont, Sara Pigazzini, Lindokuhle Nkambule, Michelle Daya, Jonathan Shortt, Nicholas Rafaels, Stephen J. Wicks, Kristy Crooks, Kathleen C. Barnes, Christopher R. Gignoux, Sameer Chavan, Triin Laisk, Kristi Läll, Maarja Lepamets, Reedik Mägi, Tõnu Esko, Ene Reimann, Lili Milani, Helene Alavere, Kristjan Metsalu, Mairo Puusepp, Andres Metspalu, Paul Naaber, Edward Laane, Jaana Pesukova, Pärt Peterson, Kai Kisand, Jekaterina Tabri, Raili Allos, Kati Hensen, Joel Starkopf, Inge Ringmets, Anu Tamm, Anne Kallaste, Pierre-Yves Bochud, Carlo Rivolta, Stéphanie Bibert, Mathieu Quinodoz, Dhryata Kamdar, Noémie Boillat, Semira Gonseth Nussle, Werner Albrich, Noémie Suh, Dionysios Neofytos, Véronique Erard, Cathy Voide, null FHoGID, null RegCOVID, null P-PredictUs, null SeroCOVID, null CRiPSI, Rafael de Cid, Iván Galván-Femenía, Natalia Blay, Anna Carreras, Beatriz Cortés, Xavier Farré, Lauro Sumoy, Victor Moreno, Josep Maria Mercader, Marta Guindo-Martinez, David Torrents, Manolis Kogevinas, Judith Garcia-Aymerich, Gemma Castaño-Vinyals, Carlota Dobaño, Alessandra Renieri, Francesca Mari, Chiara Fallerini, Sergio Daga, Elisa Benetti, Margherita Baldassarri, Francesca Fava, Elisa Frullanti, Floriana Valentino, Gabriella Doddato, Annarita Giliberti, Rossella Tita, Sara Amitrano, Mirella Bruttini, Susanna Croci, Ilaria Meloni, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Giada Beligni, Andrea Tommasi, Laura Di Sarno, Maria Palmieri, Miriam Lucia Carriero, Diana Alaverdian, Stefano Busani, Raffaele Bruno, Marco Vecchia, Mary Ann Belli, Nicola Picchiotti, Maurizio Sanarico, Marco Gori, Simone Furini, Stefania Mantovani, Serena Ludovisi, Mario Umberto Mondelli, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Massimo Vaghi, Stefano Rusconi, Matteo Siano, Francesca Montagnani, Arianna Emiliozzi, Massimiliano Fabbiani, Barbara Rossetti, Elena Bargagli, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Maria Bandini, Gian Piero Caldarelli, Paolo Piacentini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Massimo Girardis, Sophie Venturelli, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Stefano Baratti, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Giuseppe Merla, Gabriella Maria Squeo, Filippo Aucella, Pamela Raggi, Carmen Marciano, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Serafina Valente, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Sandro Mancarella, Luisa Tavecchia, Lia Crotti, Chiara Gabbi, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Stefano Ceri, Pietro Pinoli, Francesco Raimondi, Filippo Biscarini, Alessandra Stella, Kristina Zguro, Katia Capitani, Claudia Suardi, Simona Dei, Gianfranco Parati, Sabrina Ravaglia, Rosangela Artuso, Giordano Bottà, Paolo Di Domenico, Ilaria Rancan, Antonio Perrella Francesco Bianchi, Davide Romani, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Marco Tanfoni, Antonella Vincenti, Claudio Ferri, Davide Grassi, Gloria Pessina, Mario Tumbarello, Massimo Di Pietro, Ravaglia Sabrina, Sauro Luchi, Chiara Barbieri, Donatella Acquilini, Elena Andreucci, Francesco Vladimiro Segala, Giusy Tiseo, Marco Falcone, Mirjam Lista, Monica Poscente, Oreste De Vivo, Paola Petrocelli, Alessandra Guarnaccia, Silvia Baroni, Albert V. Smith, Andrew P. Boughton, Kevin W. Li, Jonathon LeFaive, Aubrey Annis, Anne E. Justice, Tooraj Mirshahi, Geetha Chittoor, Navya Shilpa Josyula, Jack A. Kosmicki, Manuel A.R. Ferreira, Joseph B. Leader, Dave J. Carey, Matthew C. Gass, Julie E. Horowitz, Michael N. Cantor, Ashish Yadav, Aris Baras, Goncalo R. Abecasis, David A. van Heel, Karen A. Hunt, Dan Mason, Qin Qin Huang, Sarah Finer, null Genes & Health Research Team, Bhavi Trivedi, Christopher J. Griffiths, Hilary C. Martin, John Wright, Richard C. Trembath, Nicole Soranzo, Jing Hua Zhao, Adam S. Butterworth, John Danesh, Emanuele Di Angelantonio, Lude Franke Marike Boezen, Patrick Deelen, Annique Claringbould, Esteban Lopera, Robert Warmerdam, Judith.M. Vonk, Irene van Blokland, Pauline Lanting, Anil P.S. Ori, Brooke Wolford Sebastian Zöllner, Jiongming Wang, Andrew Beck, Gina Peloso, Yuk-Lam Ho, Yan V. Sun, Jennifer E. Huffman, Christopher J. O’Donnell, Kelly Cho, Phil Tsao, J. Michael Gaziano, Michel (M.G.) Nivard, Eco (E.J.C.) de geus, Meike Bartels, Jouke Jan Hottenga, Scott T. Weiss, Elizabeth W. Karlson, Jordan W. Smoller, Robert C. Green, Yen-Chen Anne Feng, Josep Mercader, Shawn N. Murphy, James B. Meigs, Ann E. Woolley, Emma F. Perez, Daniel Rader, Anurag Verma, Marylyn D. Ritchie, Binglan Li, Shefali S. Verma, Anastasia Lucas, Yuki Bradford, Hugo Zeberg, Robert Frithiof, Michael Hultström, Miklos Lipcsey, Lindo Nkambul, Nicolas Tardif, Olav Rooyackers, Jonathan Grip, Tomislav Maricic, Konrad J. Karczewski, Elizabeth G. Atkinson, Kristin Tsuo, Nikolas Baya, Patrick Turley, Rahul Gupta, Shawneequa Callier, Raymond K. Walters, Duncan S. Palmer, Gopal Sarma, Nathan Cheng, Wenhan Lu, Sam Bryant, Claire Churchhouse, Caroline Cusick, Jacqueline I. Goldstein, Daniel King, Cotton Seed, Hilary Finucane, Alicia R. Martin, F. Kyle Satterstrom, Daniel J. Wilson, Jacob Armstrong, Justine K. Rudkin, Gavin Band, Sarah G. Earle, Shang-Kuan Lin, Nicolas Arning, Derrick W. Crook, David H. Wyllie, Anne Marie O’Connell, Chris C.A. Spencer, Nils Koelling, Mark J. Caulfield, Richard H. Scott, Tom Fowler, Loukas Moutsianas, Athanasios Kousathanas, Dorota Pasko, Susan Walker, Augusto Rendon, Alex Stuckey, Christopher A. Odhams, Daniel Rhodes, Georgia Chan, Prabhu Arumugam, Catherine A. Ball, Eurie L. Hong, Kristin Rand, Ahna Girshick, Harendra Guturu, Asher Haug Baltzell, Genevieve Roberts, Danny Park, Marie Coignet, Shannon McCurdy, Spencer Knight, Raghavendran Partha, Brooke Rhead, Miao Zhang, Nathan Berkowitz, Michael Gaddis, Keith Noto, Luong Ruiz, Milos Pavlovic, Laura G. Sloofman, Alexander W. Charney, Noam D. Beckmann, Eric E. Schadt, Daniel M. Jordan, Ryan C. Thompson, Kyle Gettler, Noura S. Abul-Husn, Steven Ascolillo, Joseph D. Buxbaum, Kumardeep Chaudhary, Judy H. Cho, Yuval Itan, Eimear E. Kenny, Gillian M. Belbin, Stuart C. Sealfon, Robert P. Sebra, Irene Salib, Brett L. Collins, Tess Levy, Bari Britvan, Katherine Keller, Lara Tang, Michael Peruggia, Liam L. Hiester, Kristi Niblo, Alexandra Aksentijevich, Alexander Labkowsky, Avromie Karp, Menachem Zlatopolsky, Michael Preuss, Ruth J.F. Loos, Girish N. Nadkarni, Ron Do, Clive Hoggart, Sam Choi, Slayton J. Underwood, Paul O’Reilly, Laura M. Huckins, Marissa Zyndorf, AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Neurology

Subjects
Medical Physiology, Gene Expression, Genome-wide association study, Genome, Severity of Illness Index, colocalization, Gene expression, Databases, Genetic, Ethnicity, 2.1 Biological and endogenous factors, GWAS, Aetiology, Biology (General), Lung, Genetics, Chromosome Mapping, Single Nucleotide, Organ Specificity, Biotechnology, Cell type, QH301-705.5, Quantitative Trait Loci, Single-nucleotide polymorphism, Biology, eQTL, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Databases, Genetic, SNP, Humans, Genetic Predisposition to Disease, COVID-19 Host Genetics Initiative, Polymorphism, Gene, COVID-19, SARS-CoV-2, Gene Expression Profiling, Prevention, Human Genome, Computational Biology, Genetic Variation, Good Health and Well Being, Expression quantitative trait loci, Biochemistry and Cell Biology, Transcriptome, Genome-Wide Association Study
Abstract

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types., Graphical abstract, D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.

Published
2022
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27. Author response: Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study

Author

Diego Ripamonti, Sandro Panese, Agnese Verzuri, Giancarlo Bosio, Francesco Castelli, Leonardo Croci, Maurizio Spagnesi, Sergio Daga, Massimiliano Fabbiani, Barbara Rossetti, Silvia Cappelli, Giada Beligni, Gabriella Coiro, Antonio Di Biagio, Domenico A Coviello, Massimo Girardis, Pamela Raggi, Roberta Russo, Federico Franchi, Matteo Bassetti, Stefano Baratti, Gianfranco Parati, Francesca Montagnani, Marco Rizzi, Eugenia Quiros-Roldan, Francesca Fava, Tiziana Bachetti, Agostino Riva, Filippo Aucella, Francesca Gatti, Anna Canaccini, Anna Maria Pinto, Sandro Mancarella, Alessandra Renieri, Arianna Gabrieli, Mario Chiariello, Rossella Tita, Luca Guidelli, Sophie Venturelli, Ilaria Meloni, Luisa Tavecchia, Marta Corridi, Susanna Croci, Francesca Mari, Pierpaolo Parravicini, Andrea Tommasi, Carmelo Piscopo, Tullio Trotta, Miriana d'Alessandro, Maria Antonietta Mencarelli, Cristina Mussini, Simone Furini, Alessandra Vergori, Gen-Covid Multicenter Study, Margherita Baldassarri, Daniela Francisci, Giuseppe Fiorentino, Simona Sarzi-Braga, Mirella Bruttini, Sabino Scolletta, Mario Capasso, Melania Degli Antoni, Serafina Valente, Alice Donati, Maria Antonietta Mazzei, Maurizio Bussotti, Chiara Fallerini, Laura Di Sarno, Federico Anedda, Davide Romani, Katia Capitani, Gian Piero Caldarelli, Elisa Frullanti, Caterina Lo Rizzo, Bruno Frediani, Marco Castori, Arianna Emiliozzi, Andrea Cossarizza, Elena Desanctis, Luca Cantarini, Cesira Nencioni, Ottavia Spiga, Fabio Lena, Isabella Zanella, Genni Spargi, Francesco Paciosi, Pier Giorgio Scotton, Simona Dei, Marco Mandalà, Giacomo Zanelli, Alessia Giorli, Elena Bargagli, Maria Palmieri, Stefano Rusconi, Laura Bergantini, Ferdinando Giannattasio, David Bennett, Carmen Marciano, Chiara Spertilli, Maria Bandini, Serena Ludovisi, Enrico Martinelli, Edoardo Conticini, Valentina Anemoli, Nicola Iuso, Elisa Benetti, Matteo Siano, Achille Iolascon, Danilo Tacconi, Mario U. Mondelli, Sara Amitrano, Raffaele Scala, Paolo Piacentini, Lia Crotti, Maria Teresa La Rovere, Nicola Picchiotti, Patrizia Zucchi, Elisabetta Schiaroli, Immacolata Andolfo, Francesca Andretta, Gabriella Doddato, Annarita Giliberti, Stefano Busani, Simona Marcantonio, Antonella d'Arminio Monforte, Mary Ann Belli, Luca Masucci, Rita Perna, Chiara Gabbi, Gabriella Maria Squeo, Franco Maggiolo, Marco Feri, Susanna Guerrini, Paolo Cameli, Elisabetta Menatti, Maurizio Sanguinetti, Andrea Antinori, Lorenzo Salerni, Saverio Giuseppe Parisi, Stefania Mantovani, Floriana Valentino, Federica Gaia Miraglia, Agostino Ognibene, Marco Gori, Renzo Scaggiante, Matteo Della Monica, Giuseppe Merla, Massimo Vaghi, and Massimo Carella

Subjects
Toll-like receptor, Coronavirus disease 2019 (COVID-19), business.industry, Association (object-oriented programming), Nested case-control study, Immunology, Medicine, Disease, business
Published
2021
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28. Hbcab positivity is a risk factor for an increased detectability of hiv rna after switching to a two-drug regimen lamivudine-based (2dr-3tc-based) treatment: Analysis of a multicenter italian cohort

Author

Monica Basso, Saverio Giuseppe Parisi, Mirko Compagno, Marco Iannetta, Maria Cristina Rossi, Massimo Andreoni, Elisabetta Teti, Renzo Scaggiante, Giuliana Battagin, Romina Salpini, Luigi Michele Coppola, Loredana Sarmati, Valentina Svicher, Vincenzo Malagnino, Daniela Zago, and Sandro Panese

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Dual therapy, 030106 microbiology, Viremia, Logistic regression, Settore MED/04, Microbiology, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, HIV/HBV coinfection, Virology, Internal medicine, Medicine, 030212 general & internal medicine, Risk factor, Drug regimen, lcsh:QH301-705.5, biology, business.industry, Lamivudine, virus diseases, medicine.disease, 3TC/DTG, Regimen, lcsh:Biology (General), 2DR, Cohort, biology.protein, Antibody, business, Anti-HBc, medicine.drug
Abstract

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: &lt, 31% vs 17.6%, p = 0.047, 12th month 34% vs 27.5%, p = 0.001, 24th month 37% vs 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs 11%, p = 0.001, 24 months 37% vs 13.9%, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that an increase in age of ten years (OR 2.48 (95% CI 1.58–3.89), p &lt, 0.0001) and the presence of HBcAb positivity (OR 2.7 (5% CI 1.05–6.9), p = 0.038) increased the risk of detectability of HIV RNA by nearly three-fold after switching to 2DR-3TC.

Published
2021

29. Genetic mechanisms of critical illness in COVID-19

Author

Pairo-Castineira, Erola, Clohisey, Sara, Klaric, Lucija, Bretherick, Andrew D, Rawlik, Konrad, Pasko, Dorota, Walker, Susan, Parkinson, Nick, Fourman, Max Head, Russell, Clark D, Furniss, James, Richmond, Anne, Gountouna, Elvina, Wrobel, Nicola, Harrison, David, Wang, Bo, Yang, Wu, Meynert, Alison, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Moutsianas, Loukas, Yang, Zhijian, Zhai, Ranran, Zheng, Chenqing, Grimes, Graeme, Beale, Rupert, Millar, Jonathan, Shih, Barbara, Keating, Sean, Zechner, Marie, Haley, Chris, Porteous, David J, Hayward, Caroline, Yang, Jian, Knight, Julian, Summers, Charlotte, Shankar-Hari, Manu, Klenerman, Paul, Turtle, Lance, Antonia, Ho, Moore, Shona C, Hinds, Charles, Horby, Peter, Nichol, Alistair, Maslove, David, Ling, Lowell, Mcauley, Danny, Montgomery, Hugh, Walsh, Timothy, Pereira, Alexandre C, Renieri, Johnny, Millar, Alistair, Nichol, Tim, Walsh, Manu, Shankar-Hari, Chris, Ponting, Jen, Meikle, Paul, Finernan, Ellie, Mcmaster, Andy, Law, J Kenneth Baillie, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Nicholas, Parkinson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthope, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, C, Marotti, M, Arbane, G, Bonner, S, Hugill, K, Reid, J, Welters, I, Waugh, V, Williams, K, Shaw, D, J Fernandez Roman, M Lopez Martinez, Johnson, E, Waite, A, Johnston, B, Hamilton, D, Mulla, S, Mcphail, M, Smith, J, K Baillie, J, Barclay, L, Hope, D, Mcculloch, C, Mcquillan, L, Clark, S, Singleton, J, Priestley, K, Rea, N, Callaghan, M, Campbell, R, Andrew, G, Marshall, L, Mckechnie, S, Hutton, P, Bashyal, A, Davidson, N, Summers, C, Polgarova, P, Stroud, K, Pathan, N, Elston, K, Agrawal, S, Battle, C, Newey, L, Rees, T, Harford, R, Brinkworth, E, Williams, M, Murphy, C, White, I, Croft, M, Bandla, N, Gellamucho, M, Tomlinson, J, Turner, H, Davies, M, Quinn, A, Hussain, I, Thompson, C, Parker, H, Bradley, R, Griffiths, R, Scriven, J, Nilsson, A, Bates, M, Dasgin, J, Gill, J, Puxty, A, Cathcart, S, Salutous, D, Turner, L, Duffy, K, Puxty, K, Joseph, A, Herdman-Grant, R, Simms, R, Swain, A, Naranjo, A, Crowe, R, Sollesta, K, Loveridge, A, Baptista, D, Morino, E, Davey, M, Golden, D, Jones, J, J Moreno Cuesta, Haldeos, A, Bakthavatsalam, D, Vincent, R, Elhassan, M, Xavier, K, Ganesan, A, Purohit, D, Abdelrazik, M, Morgan, J, Akeroyd, L, Bano, S, Lawton, T, Warren, D, Bromley, M, Sellick, K, Gurr, L, Wilkinson, B, Nagarajan, V, Szedlak, P, Cupitt, J, Stoddard, E, Benham, L, Preston, S, Laha, S, Slawson, N, Bradshaw, Z, Brown, J, Caswell, M, Melling, S, Bamford, P, Faulkner, M, Cawley, K, Jeffrey, H, London, E, Sainsbury, H, Nagra, I, Nasir, F, Dunmore, C, Jones, R, Abraheem, A, Al-Moasseb, M, Girach, R, Padden, G, Egan, J, Brantwood, C, Alexander, P, Bradley-Potts, J, Allen, S, Felton, T, Manna, S, Farnell-Ward, S, Leaver, S, Queiroz, J, Maccacari, E, Dawson, D, C Castro Delgado, R Pepermans Saluzzio, Ezeobu, O, Ding, L, Sicat, C, Kanu, R, Durrant, G, Texeira, J, Harrison, A, Samakomva, T, Willis, H, Hopkins, B, Thrasyvoulou, L, Jackson, M, Zaki, A, Tibke, C, Bennett, S, Woodyatt, W, Kent, A, Goodwin, E, Brandwood, C, Clark, R, Smith, L, Rooney, K, Thomson, N, Rodden, N, Hughes, E, Mcglynn, D, Clark, C, Clark, P, Abel, L, Sundaram, R, Gemmell, L, Brett, M, Hornsby, J, Macgoey, P, Price, R, Digby, B, O'Neil, P, Mcconnell, P, Henderson, P, Henderson, S, Sim, M, Kennedy-Hay, S, Mcparland, C, Rooney, L, Baxter, N, Pogson, D, Rose, S, Daly, Z, Brimfield, L, K Phull, M, Hussain, M, Pogreban, T, Rosaroso, L, Salciute, E, Grauslyte, L, Brealey, D, Raith, E, Maccallum, N, Bercades, G, Hass, I, Smyth, D, Reyes, A, Martir, G, D Clement, I, Webster, K, Hays, C, Gulati, A, Hodgson, L, Margarson, M, Gomez, R, Baird, Y, Thirlwall, Y, Folkes, L, Butler, A, Meadows, E, Moore, S, Raynard, D, Fox, H, Riddles, L, King, K, Kimber, S, Hobden, G, Mccarthy, A, Cannons, V, Balagosa, I, Chadbourn, I, Gardner, A, Horner, D, Mclaughlanv, D, Charles, B, Proudfoot, N, Marsden, T, Mcmorrow, L, Blackledge, B, Pendlebury, J, Harvey, A, Apetri, E, Basikolo, C, Catlow, L, Doonan, R, Knowles, K, Lee, S, Lomas, D, Lyons, C, Perez, J, Poulaka, M, Slaughter, M, Slevin, K, Thomas, V, Walker, D, Harris, J, Drummond, A, Tully, R, Dearden, J, Philbin, J, Munt, S, Rishton, C, O'Connor, G, Mulcahy, M, Dobson, E, Cuttler, J, Edward, M, Norris, J, Hanson, K, Poole, A, Rose, A, Sloan, B, Buckley, S, Brooke, H, Smithson, E, Charlesworth, R, Sandhu, R, Thirumaran, M, Wagstaff, V, J Cebrian Suarez, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Solesbury, A, Kittridge, L, Forsey, M, Maloney, G, Cole, J, Davies, R, Hill, H, Thomas, E, Williams, A, Duffin, D, Player, B, Radhakrishnan, J, Gibson, S, Lyle, A, Mcneela, F, Patel, B, Gummadi, M, Sloane, G, Dormand, N, Salmi, S, Farzad, Z, Cristiano, D, Liyanage, K, Thwaites, V, Varghese, M, Meredith, M, Mills, G, Willson, J, Harrington, K, Lenagh, B, Cawthron, K, Masuko, S, Raithatha, A, Bauchmuller, K, Wiles, M, Ahmad, N, Barker, J, Jackson, Y, Kibutu, F, Bird, S, Watson, G, Martin, J, Bevan, E, C Wrey Brown, Trodd, D, English, K, Bell, G, Wilcox, L, Katary, A, Gopal, S, Lake, V, Harris, N, Metherell, S, Radford, E, Moore, F, Bancroft, H, Daglish, J, Sangombe, M, Carmody, M, Rhodes, J, Bellamy, M, Garg, A, Kuravi, A, Virgilio, E, Ranga, P, Butler, J, Botfield, L, Dexter, C, Fletcher, J, Shanmugasundaram, P, Hambrook, G, Burn, I, Manso, K, Thornton, D, Tebbutt, J, Penn, R, Hulme, J, Hussain, S, Maqsood, Z, Joseph, S, Colley, J, Hayes, A, Ahmed, C, Haq, R, Clamp, S, Kumar, R, Purewal, M, Baines, B, Frise, M, Jacques, N, Coles, H, Caterson, J, S Gurung Rai, Brunton, M, Tilney, E, Keating, L, Walden, A, Antcliffe, D, Brett, S, Gordon, A, Templeton, M, Rojo, R, Banach, D, S Sousa Arias, Fernandez, Z, Coghlan, P, Williams, D, Jardine, C, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Garland, Z, Gumbrill, B, Phillips, C, L Ortiz-Ruiz de Gordoa, Peasgood, E, Tridente, A, Shuker, K, Greer, S, Lynch, C, Pothecary, C, Roche, L, Deacon, B, Turner, K, Singh, J, G Sera Howe, Paul, P, Gill, M, Wynter, I, Ratnam, V, Shelton, S, Naisbitt, J, Melville, J, Baruah, R, Morrison, S, Mcgregor, A, Parris, V, Mpelembue, M, Srikaran, S, Dennis, C, Sukha, A, Verlander, M, Holding, K, Riches, K, Downes, C, Swan, C, Rostron, A, Roy, A, Woods, L, Cornell, S, Wakinshaw, F, Creagh-Brown, B, Blackman, H, Salberg, A, Smith, E, Donlon, S, Mtuwa, S, Michalak-Glinska, N, Stone, S, Beazley, C, Pristopan, V, Nikitas, N, Lankester, L, Wells, C, S Raj, A, Fletcher, K, Khade, R, Tsinaslanidis, G, Macmahon, M, Fowler, S, Coventry, T, Stewart, R, Wren, L, Mwaura, E, Mew, L, Scaletta, D, Williams, F, Inweregbu, K, Lancaster, N, Cunningham, M, Daniels, A, Harrison, L, Hope, S, Jones, S, Crew, A, Wray, G, Matthews, J, Crawley, R, Carter, J, Birkinshaw, I, Ingham, J, Scott, Z, Pearson, H, Howard, K, Joy, R, Roche, S, Clark, M, Purvis, S, Morrison, A, Strachan, D, Clements, S, Black, K, Parmar, C, Altabaibeh, A, Simpson, K, Mostoles, L, Gilbert, K, L, Ma, Alvaro, A, Thomas, M, Faulkner, B, Worner, R, Hayes, K, Gendall, E, Blakemore, H, Borislavova, B, Goff, E, Vuylsteke, A, Mwaura, L, Zamikula, J, Garner, L, Mitchell, A, Mepham, S, Cagova, L, Fofano, A, Holcombe, H, Praman, K, Szakmany, T, E Heron, A, Cherian, S, Cutler, S, Roynon-Reed, A, Randell, G, Convery, K, Stammers, K, Fottrell-Gould, D, Hudig, L, Keshet-Price, J, Peters, M, O'Neill, L, Ray, S, Belfield, H, Mchugh, T, Jones, G, Akinkugbe, O, Tomas, A, Abaleke, E, Beech, E, Meghari, H, Yussuf, S, Bamford, A, Hairsine, B, Dooks, E, Farquhar, F, Packham, S, Bates, H, Armstrong, L, Kaye, C, Allan, A, Medhora, J, Liew, J, Botello, A, Anderson, F, Cusack, R, Golding, H, Prager, K, Williams, T, Leggett, S, Golder, K, Male, M, Jones, O, Criste, K, Marani, M, Anumakonda, V, Amin, V, Karthik, K, Kausar, R, Anastasescu, E, Reid, K, Smith, M, Hormis, A, Walker, R, Duncan, T, Uriel, A, Ustianowski, A, T-Michael, H, Bruce, M, Connolly, K, Smith, K, Partridge, R, Griffin, D, Mupudzi, M, Muchenje, N, Martin, D, Filipe, H, Eastgate, C, Jackson, C, Gratrix, A, Foster, L, Martinson, V, Stones, E, Caroline, Abernathy, Parkinson, P, Reed, A, Prendergast, C, Rogers, P, 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Watters, M, Langton, H, Prout, R, Page, V, Varghes, T, Cowton, A, Kay, A, Potts, K, Birt, M, Kent, M, Wilkinson, A, B Jude, E, Turner, V, Savill, H, Mccormick, J, Coulding, M, Siddiqui, S, Mercer, O, Rehman, H, Potla, D, Capps, N, Donaldson, D, Button, H, Martin, T, Hard, K, Agasou, A, Tonks, L, Arden, T, Boyle, P, Carnahan, M, Strickley, J, Adams, C, Childs, D, Rikunenko, R, Leigh, M, Breekes, M, Wilcox, R, Bowes, A, Tiveran, H, Hurford, F, Summers, J, Carter, A, Hussain, Y, Ting, L, Javaid, A, Motherwell, N, Moore, H, Millward, H, Jose, S, Schunki, N, Noakes, A, Clulow, C, Sadera, G, Jacob, R, Jones, C, Blunt, M, Coton, Z, Curgenven, H, S Mohamed Ally, Beaumont, K, Elsaadany, M, Fernandes, K, I Ali Mohamed Ali, Rangarajan, H, Sarathy, V, Selvanayagam, S, Vedage, D, White, M, Truman, N, Chukkambotla, S, Keith, S, Cockerill-Taylor, J, Ryan-Smith, J, Bolton, R, Springle, P, Dykes, J, Thomas, J, Khan, M, T Hijazi, M, Massey, E, Croston, G, Reschreiter, H, Camsooksai, J, Patch, S, 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W., Trodd, D., English, K., Bell, G., Wilcox, L., Katary, A., Gopal, S., Lake, V., Harris, N., Metherell, S., Radford, E., Moore, F., Bancroft, H., Daglish, J., Sangombe, M., Carmody, M., Rhodes, J., Bellamy, M., Garg, A., Kuravi, A., Virgilio, E., Ranga, P., Butler, J., Botfield, L., Dexter, C., Fletcher, J., Shanmugasundaram, P., Hambrook, G., Burn, I., Manso, K., Thornton, D., Tebbutt, J., Penn, R., Hulme, J., Hussain, S., Maqsood, Z., Joseph, S., Colley, J., Hayes, A., Ahmed, C., Haq, R., Clamp, S., Kumar, R., Purewal, M., Baines, B., Frise, M., Jacques, N., Coles, H., Caterson, J., Rai, S. G., Brunton, M., Tilney, E., Keating, L., Walden, A., Antcliffe, D., Brett, S., Gordon, A., Templeton, M., Rojo, R., Banach, D., Arias, S. S., Fernandez, Z., Coghlan, P., Williams, D., Jardine, C., Bewley, J., Sweet, K., Grimmer, L., Johnson, R., Garland, Z., Gumbrill, B., Phillips, C., Ortiz-Ruiz de Gordoa, L., Peasgood, E., Tridente, A., Shuker, K., Greer, S., Lynch, C., Pothecary, C., Roche, L., Deacon, B., Turner, K., Singh, J., Howe, G. S., Paul, P., Gill, M., Wynter, I., Ratnam, V., Shelton, S., Naisbitt, J., Melville, J., Baruah, R., Morrison, S., Mcgregor, A., Parris, V., Mpelembue, M., Srikaran, S., Dennis, C., Sukha, A., Verlander, M., Holding, K., Riches, K., Downes, C., Swan, C., Rostron, A., Roy, A., Woods, L., Cornell, S., Wakinshaw, F., Creagh-Brown, B., Blackman, H., Salberg, A., Smith, E., Donlon, S., Mtuwa, S., Michalak-Glinska, N., Stone, S., Beazley, C., Pristopan, V., Nikitas, N., Lankester, L., Wells, C., Raj, A. S., Fletcher, K., Khade, R., Tsinaslanidis, G., Macmahon, M., Fowler, S., Coventry, T., Stewart, R., Wren, L., Mwaura, E., Mew, L., Scaletta, D., Williams, F., Inweregbu, K., Lancaster, N., Cunningham, M., Daniels, A., Harrison, L., Hope, S., Jones, S., Crew, A., Wray, G., Matthews, J., Crawley, R., Carter, J., Birkinshaw, I., Ingham, J., Scott, Z., Pearson, H., Howard, K., Joy, R., Roche, S., Clark, M., Purvis, S., Morrison, A., Strachan, D., Clements, S., Black, K., Parmar, C., Altabaibeh, A., Simpson, K., Mostoles, L., Gilbert, K., Ma, L., Alvaro, A., Thomas, M., Faulkner, B., Worner, R., Hayes, K., Gendall, E., Blakemore, H., Borislavova, B., Goff, E., Vuylsteke, A., Mwaura, L., Zamikula, J., Garner, L., Mitchell, A., Mepham, S., Cagova, L., Fofano, A., Holcombe, H., Praman, K., Szakmany, T., Heron, A. E., Cherian, S., Cutler, S., Roynon-Reed, A., Randell, G., Convery, K., Stammers, K., Fottrell-Gould, D., Hudig, L., Keshet-Price, J., Peters, M., O'Neill, L., Ray, S., Belfield, H., Mchugh, T., Jones, G., Akinkugbe, O., Tomas, A., Abaleke, E., Beech, E., Meghari, H., Yussuf, S., Bamford, A., Hairsine, B., Dooks, E., Farquhar, F., Packham, S., Bates, H., Armstrong, L., Kaye, C., Allan, A., Medhora, J., Liew, J., Botello, A., Anderson, F., Cusack, R., Golding, H., Prager, K., Williams, T., Leggett, S., Golder, K., Male, M., Jones, O., Criste, K., Marani, M., Anumakonda, V., Amin, V., Karthik, K., Kausar, R., Anastasescu, E., Reid, K., Smith, M., Hormis, A., Walker, R., Duncan, T., Uriel, A., Ustianowski, A., T-Michael, H., Bruce, M., Connolly, K., Smith, K., Partridge, R., Griffin, D., Mupudzi, M., Muchenje, N., Martin, D., Filipe, H., Eastgate, C., Jackson, C., Gratrix, A., Foster, L., Martinson, V., Stones, E., Abernathy, C., Parkinson, P., Reed, A., Prendergast, C., Rogers, P., Woodruff, M., Shokkar, R., Kaul, S., Barron, A., Collins, C., Beavis, S., Whileman, A., Dale, K., Hawes, J., Pritchard, K., Gascoyne, R., Stevenson, L., Jha, R., Lim, L., Krishnamurthy, V., Parker, R., Turner-Bone, I., Wilding, L., Reddy, A., Whiteley, S., Wilby, E., Howcroft, C., Aspinwall, A., Charlton, S., Ogg, B., Menzies, D., Pugh, R., Allan, E., Lean, R., Davies, F., Easton, J., Qiu, X., Kumar, S., Darlington, K., Houston, G., O'Brien, P., Geary, T., Allan, J., Meikle, A., Hughes, G., Balasubramaniam, M., Latham, S., Mckenna, E., Flanagan, R., Sathe, S., Davies, E., Chablani, M., Kirkby, A., Netherton, K., Archer, S., Yates, B., Ashbrook-Raby, C., Cole, S., Casey, M., Cabrelli, L., Chapman, S., Hutcheon, A., Whyte, C., Almaden-Boyle, C., Pattison, N., Cruz, C., Vochin, A., Kent, H., Thomas, A., Murdoch, S., David, B., Penacerrada, M., Lubimbi, G., Bastion, V., Wulandari, R., Lorusso, R., Valentine, J., Clarke, D., Serrano-Ruiz, A., Hierons, S., Eckbad, C., Ramos, L., Demetriou, C., Mitchard, S., White, K., White, N., Pitts, S., Branney, D., Frankham, J., Watters, M., Langton, H., Prout, R., Page, V., Varghes, T., Cowton, A., Kay, A., Potts, K., Birt, M., Kent, M., Wilkinson, A., Jude, E. B., Turner, V., Savill, H., Mccormick, J., Coulding, M., Siddiqui, S., Mercer, O., Rehman, H., Potla, D., Capps, N., Donaldson, D., Button, H., Martin, T., Hard, K., Agasou, A., Tonks, L., Arden, T., Boyle, P., Carnahan, M., Strickley, J., Adams, C., Childs, D., Rikunenko, R., Leigh, M., Breekes, M., Wilcox, R., Bowes, A., Tiveran, H., Hurford, F., Summers, J., Carter, A., Hussain, Y., Ting, L., Javaid, A., Motherwell, N., Moore, H., Millward, H., Jose, S., Schunki, N., Noakes, A., Clulow, C., Sadera, G., Jacob, R., Jones, C., Blunt, M., Coton, Z., Curgenven, H., Ally, S. M., Beaumont, K., Elsaadany, M., Fernandes, K., Ali Mohamed Ali, I., Rangarajan, H., Sarathy, V., Selvanayagam, S., Vedage, D., White, M., Truman, N., Chukkambotla, S., Keith, S., Cockerill-Taylor, J., Ryan-Smith, J., Bolton, R., Springle, P., Dykes, J., Thomas, J., Khan, M., Hijazi, M. T., Massey, E., Croston, G., Reschreiter, H., Camsooksai, J., Patch, S., Jenkins, S., Humphrey, C., Wadams, B., Msiska, M., Adanini, O., Attwood, B., Parsons, P., Tatham, K., Jhanji, S., Black, E., Dela Rosa, A., Howle, R., Thomas, B., Bemand, T., Raobaikady, R., Saha, R., Staines, N., Daniel, A., Finn, J., Hutter, J., Doble, P., Shovelton, C., Pawley, C., Kannan, T., Hill, M., Combes, E., Monnery, S., Joefield, T., Popescu, M., Thankachen, M., Oblak, M., Little, J., Mcivor, S., Brady, A., Whittle, H., Prady, H., Chan, R., Ahmed, A., Morris, A., Gibson, C., Gordon, E., Keenan, S., Quinn, H., Benyon, S., Marriott, S., Zitter, L., Park, L., Baines, K., Lyons, M., Holland, M., Keenan, N., Young, M., Garrioch, S., Dawson, J., Tolson, M., Scholefield, B., Bi, R., Richardson, N., Schumacher, N., Cosier, T., Millen, G., Higham, A., Turki, S., Allen, L., Crisp, N., Hazleton, T., Knight, A., Deery, J., Price, C., Turney, S., Tilbey, S., Beranova, E., Wright, D., George, L., Twiss, S., Wadd, S., Postlethwaite, K., Gondo, P., Masunda, B., Kayani, A., Hadebe, B., Whiteside, J., Clarke, N., Donnison, P., Trim, F., Leadbitter, I., Butcher, D., O'Sullivan, S., Purewal, B., Bell, S., Rivers, V., O'Leary, R., Birch, J., Collins, E., Anderson, S., Hammerton, K., Andrews, E., Burns, K., Edmond, I., Todd, A., Donnachie, J., Turner, P., Prentice, L., Symon, L., Runciman, N., Auld, F., Halkes, M., Mercer, P., Thornton, L., Debreceni, G., Wilkins, J., Crickmore, V., Subramanian, G., Marshall, R., Jennings, C., Latif, M., Bunni, L., Spivey, M., Bean, S., Burt, K., Linnett, V., Ritzema, J., Sanderson, A., Mccormick, W., Bokhari, M., Kapoor, R., Loader, D., Ayers, A., Harrison, W., North, J., Belagodu, Z., Paramsothy, R., Olufuwa, O., Gherman, A., Fuller, B., Stuart, C., Kelsall, O., Davis, C., Wild, L., Wood, H., Thrush, J., Durie, A., Austin, K., Archer, K., Anderson, P., Vigurs, C., Thorpe, C., Knights, E., Boyle, N., Price, A., Kubisz-Pudelko, A., Wood, D., Lewis, A., Board, S., Pippard, L., Perry, J., Beesley, K., Rattray, A., Lee, E., Lennon, L., Douglas, K., Bell, D., Boyle, R., Glass, L., Nauman Akhtar, M., Dent, K., Potoczna, D., Pearson, S., Horsley, E., Spencer, S., Mullan, D., Skinner, D., Gaylard, J., Barber, R., Hewitt, C., Hilldrith, A., Shepardson, S., Wills, M., Jackson-Lawrence, K., Gupta, A., Timlick, E., Gorman, C., Otahal, I., Gales, A., Coetzee, S., Sell, C., Raj, M., Peiu, M., Quaid, S., Watson, E., Elliott, K., Mallinson, J., Chandler, B., Turnbull, A., Finch, C., Holl, C., Cooper, J., Evans, A., Khaliq, W., Collins, A., Gude, E. T., Love, N., van Koutrik, L., Hunt, J., Kaye, D., Fisher, E., Brayne, A., Tuckey, V., Jackson, P., Parkin, J., Tariq, A., Houlden, H., Tucci, A., Hardy, J., Moncur, E., Highgate, J., Cowley, A., Mitra, A., Stead, R., Behan, T., Burnett, C., Newton, M., Heeney, E., Pollard, R., Hatton, J., Patel, A., Kasipandian, V., Allibone, S., Genetu, R. M., O'Brien, L., Omar, Z., Perkins, E., Davies, K., Tetla, D., Shelley, B., Irvine, V., Williams, S., Williams, P., Goodsell, J., Tutton, R., Bough, L., Winter-Goodwin, B., Kitson, R., Pinnell, J., Wilson, A., Nortcliffe, T., Wood, T., Home, M., Holdroyd, K., Robinson, M., Shaw, R., Greig, J., Brady, M., Haigh, A., Matupe, L., Usher, M., Mellor, S., Dale, S., Gledhill, L., Shaw, L., Turner, G., Kelly, D., Anwar, B., Riley, H., Sturgeon, H., Ali, A., Thomis, L., Melia, D., Dance, A., Humphreys, S., Frost, I., Gopal, V., Godden, J., Holden, A., Swann, S., Smith, T., Clapham, M., Poultney, U., Harper, R., Rice, P., Reece-Anthony, R., Gurung, B., Moultrie, S., Odam, M., Mayer, A., Bellini, A., Pickard, A., Bryant, J., Roe, N., Sowter, J., Lang, K., Taylor, J., Barry, P., Hobrok, M., Tench, H., Wolf-Roberts, R., Mcguinness, H., Loosley, R., Hawcutt, D., Rad, L., O'Malley, L., Saunderson, P., Seddon, G., Anderson, T., Rogers, N., Ruddy, J., Harkins, M., Beith, C., Mcalpine, A., Ferguson, L., Grant, P., Macfadyen, S., Mclaughlin, M., Baird, T., Rundell, S., Welsh, B., Hamill, R., Fisher, F., Gregory, J., Campbell, A., Smuts, S., Kenneth Baillie, J., Carson, G., Alex, B., Bach, B., Barclay, W. S., Bogaert, D., Chand, M., Cooke, G. S., Docherty, A. B., Dunning, J., da Silva Filipe, A., Fletcher, T., Green, C. A., Harrison, E. M., Hiscox, J. A., Ho, A. Y. W., Horby, P. W., Ijaz, S., Khoo, S., Lim, W. S., Mentzer, A. J., Merson, L., Meynert, A. M., Noursadeghi, M., Palmarini, M., Paxton, W. A., Pollakis, G., Price, N., Rambaut, A., Robertson, D. L., Sancho-Shimizu, V., Scott, J. T., de Silva, T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Tedder, R. S., Thomson, E. C., Thompson, A. A. R., Thwaites, R. S., Turtle, L. C. W., Zambon, M., Hardwick, H., Donohue, C., Lyons, R., Norman, L., Pius, R., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Murphy, D., Shaw, C. A., Dalton, J., Girvan, M., Saviciute, E., Roberts, S., Harrison, J., Marsh, L., Connor, M., Halpin, S., Gamble, C., Leeming, G., Wham, M., Greenhalf, W., Shaw, V., Mcdonald, S., Ganna, A., Sulem, P., van Heel, D. A., Cordioli, M., Sveinbjornsson, G., Niemi, M. E. K., Shelton, J. F., Shastri, A. J., Ye, C., Weldon, C. H., Filshtein-Sonmez, T., Coker, D., Symons, A., Esparza-Gordillo, J., Aslibekyan, S., Auton, A., Krieger, J. E., Marques, E., Jannes, C. E., Mari, F., Daga, S., Baldassarri, M., Benetti, E., Furini, S., Fallerini, C., Fava, F., Valentino, F., Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Pinto, A. M., Frullanti, E., Mencarelli, M. A., Rizzo, C. L., Montagnani, F., Di Sarno, L., Tommasi, A., Palmieri, M., Emiliozzi, A., Fabbiani, M., Rossetti, B., Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, M., Cameli, P., Bennet, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Vaghi, M., D'Arminio Monforte, A., Merlini, E., Mondelli, M. U., Mantovani, S., Ludovisi, S., Girardis, M., Venturelli, S., Sita, M., Cossarizza, A., Antinori, A., Vergori, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, M. E., Magro, P., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Merla, G., Aucella, F., Raggi, P., Marciano, C., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Coviello, D. A., Mussini, C., Bosio, G., Martinelli, E., Mancarella, S., Tavecchia, L., Crotti, L., Picchiotti, N., Gori, M., Gabbi, C., Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Biscarini, F., Stella, A., Shen, X., Ponting, C. P., Fawkes, A., Tenesa, A., Caulfield, M., Scott, R., Rowan, K., Murphy, L., Openshaw, P. J. M., Semple, M. G., Vitart, V., and Wilson, J. F.

Subjects
0301 basic medicine, Male, CCR2, Chromosomes, Human, Pair 21, Genome-wide association study, Receptor, Interferon alpha-beta, Disease, Bioinformatics, Genome-wide association studies, 23andMe Investigators, Interferon alpha-beta, 0302 clinical medicine, Receptors, 2',5'-Oligoadenylate Synthetase, Pair 12, genetics, Lung, BRACOVID Investigators, Multidisciplinary, GenOMICC Investigators, Tyrosine kinase 2, 030220 oncology & carcinogenesis, Multigene Family, Medical genetics, Female, Dipeptidyl-Peptidases and Tripeptidyl-Peptidase, 5'-Oligoadenylate Synthetase, Human, Receptor, medicine.medical_specialty, Critical Care, Receptors, CCR2, General Science & Technology, Critical Illness, Chromosomes, 03 medical and health sciences, Intensive care, Mendelian randomization, Immunogenetics, medicine, Humans, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Gen-COVID Investigators, Inflammation, TYK2 Kinase, Chromosomes, Human, Pair 12, Pair 19, SARS-CoV-2, business.industry, Drug Repositioning, COVID-19, United Kingdom, COVID-19 Human Genetics Initiative, 030104 developmental biology, Viral infection, Chromosomes, Human, Pair 19, Genome-Wide Association Study, Pharmacogenomics, ISARICC Investigators, Pair 21, 2', business
Abstract

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079,P=1.65×10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1,OAS2andOAS3); on chromosome 19p13.2 (rs74956615,P=2.3×10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069,P=3.98× 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757,P=4.99×10−8) in the interferon receptor geneIFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression ofIFNAR2, or high expression ofTYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptorCCR2is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.

Published
2020
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30. Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Author

Samantha Andreis, Ermenegildo Francavilla, Vinicio Manfrin, Monica Basso, Caterina Boldrin, Mario Alvarez, Guido Antonelli, Federico Dal Bello, Ombretta Turriziani, Maria Cristina Rossi, Roberto Ferretto, Massimo Andreoni, Renzo Scaggiante, Sandro Panese, Carlo Mengoli, Mario Cruciani, Saverio Giuseppe Parisi, Loredana Sarmati, and Giorgio Palù

Subjects
Male, 0301 basic medicine, Prevalence, HIV Infections, HIV Integrase, Drug resistance, medicine.disease_cause, Strand transfer, 0302 clinical medicine, Hiv infected, Transmitted drug resistance mutations, Immunology and Allergy, 030212 general & internal medicine, Primary-recent, media_common, Mutation, Chronic HIV infection, biology, Integrase strand transfer inhibitors, Microbiology, Immunology, Microbiology (medical), Middle Aged, HIV Reverse Transcriptase, Integrase, Italy, Reverse Transcriptase Inhibitors, Female, Algorithms, Adult, Drug, Settore MED/17 - Malattie Infettive, Genotype, Anti-HIV Agents, media_common.quotation_subject, First line, 030106 microbiology, Young Adult, 03 medical and health sciences, Drug Resistance, Viral, medicine, chronic HIV infection, primary-recent, transmitted drug resistance mutations, Humans, HIV Integrase Inhibitors, Virology, HIV-1, biology.protein
Abstract

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy.

Published
2017
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31. 388. Multidrug Resistant Gram Negative Organisms Prevalence in Hospitalized Patients in an Italian Tertiary Level Hospital During COVID-19 Pandemia: First Detection is More Frequent in Clinical Samples than in Surveillance Rectal Swabs with Respect to the Previous 14-Month Period

Author

Monica Basso, Andrea Crisanti, Renzo Scaggiante, Saverio Giuseppe Parisi, Francesco Onelia, M. A. Biasolo, Elisa Franchin, E. De Canale, and Daniela Zago

Subjects
medicine.medical_specialty, Isolation (health care), biology, Klebsiella pneumoniae, business.industry, Acinetobacter, Antimicrobial, biology.organism_classification, medicine.disease, Multiple drug resistance, Pneumonia, AcademicSubjects/MED00290, Infectious Diseases, Oncology, Internal medicine, Intensive care, Poster Abstracts, medicine, Infection control, business
Abstract

Background In Italy the pandemic of COVID-19 infection has placed an enormous burden on health authorities: contact precautions are required to avoid viral transmission and people should be subjected to standard infection control procedures. This is crucial in a country experiencing a high number of confirmed cases of COVID-19 infection in Europe and where multidrug-resistant Gram-negative bacteria (MDR-GN) are endemic.The aim of this study was to compare the prevalence of MDR-GN in surveillance rectal swabs (SRS) and in clinical samples (CS) in the period March 1,2020-April, 24 2020 with respect to the previous 2-month period and to the previous year. Methods The first SRS and the first CS with a MDR-GN isolate detected from 01/01/2019 to 24/04/2020 were included. Analysis was made by comparing three different study periods in 2019 and 2020 (Jan-Dec 2019, Jan-Feb 2020, and Mar-Apr 2020), for medical department, surgical department and intensive care department. Results Overall, 612 MDR-GN organisms were identified (399 SRS and 213 CS): carbapenemase-producing Klebsiella pneumoniae and Acinetobacter baumanii (CPAB) were the most frequently detected (Figure 1). We observed an increased relative frequency of patients with MDR-GN detected in CS respect to those found in SRS (32.7% vs 44.5% vs 70.6%, p=0.0005): 5/12 CS detected in the last period were isolated from the respiratory tract (Figure 2). Nine patients with COVID-19 pneumonia had MDR-GN. All but two patients had a previous negative SRS performed 4 days before (median value) and the median interval between COVID-19 positivity and MDR-GN positivity was 7 days.The six patients with CPAB isolation were all hospitalized in the same ward, with partially overlapping hospital stays during the study period. In 5 of them, CPAB was detected in the respiratory tract (Figure 3). Conclusion The first detection of MDR-GN in CS and the nosocomial MDR-GN acquisition despite cohorting due to COVID-19 infection underline the need to reinforce infection control measures in a high prevalence country during COVID-19 pandemia. A correct antimicrobial policy urged because, according to published data, most patients with COVID-19 infection received antimicrobial therapy: furthermore MDR-GN infection could play a role in the negative outcome of these patients. Disclosures All Authors: No reported disclosures

Published
2020
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32. Intra-hospital acquisition of colonization and infection by Klebsiella pneumoniae strains producing carbapenemases and carriage evolution: A longitudinal analysis in an Italian teaching hospital from January 2017 to August 2019

Author

Saverio Giuseppe Parisi, Francesco Onelia, Elisa Baldasso, Daniela Zago, Marta Peracchi, Irene Pozzetto, Giorgio Palù, Maria Angela Biasolo, Monica Basso, Renzo Scaggiante, and Ettore De Canale

Subjects
Colonization, 0301 basic medicine, Male, Medical staff, Klebsiella pneumoniae, Colistin resistance, Drug Resistance, Tertiary Care Centers, 0302 clinical medicine, 80 and over, Medicine, 030212 general & internal medicine, Longitudinal Studies, Aged, 80 and over, Cross Infection, biology, Bacterial, General Medicine, Middle Aged, Hospitals, Anti-Bacterial Agents, Infectious Diseases, Italy, Epidemiological Monitoring, Female, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Evolution, 030106 microbiology, beta-Lactamases, Teaching hospital, Carbapenemase, 03 medical and health sciences, Nosocomial transmission, Bacterial Proteins, Intensive care, Internal medicine, parasitic diseases, Drug Resistance, Bacterial, Humans, Hospitals, Teaching, Aged, Retrospective Studies, business.industry, Colistin, Teaching, Rectum, Carbapenemase producing, biology.organism_classification, Klebsiella Infections, Carriage, business
Abstract

Objectives We present an updated picture (1/1/2017–31/08/2019) of the frequency of carbapenemase producing Klebsiella pneumoniae (CPKP) in surveillance rectal swabs (SRS) and in clinical samples (CS) of patients admitted to a tertiary level hospital, focusing on longitudinal evolution of CPKP detected in SRS and on colistin resistant strains. Methods Retrospective longitudinal analysis. Only the first positive CPKP strain isolated from each patient was included. Results 638 CPKP strains were identified (471 in SRS and 167 in CS). SRS frequency increased over time in the medical department, remained high in the surgical department (SD) and decreased in the intensive care department. Most SRS–71.3%–and 49.1% of CS had nosocomial origin; about half of the SRS were identified in the SD. Regarding SRS evolution, carriage was confirmed in 39.5% of patients, no more testing in 25.5%, clinical involvement in 24.8 %, and negative result in 10.2%. Rates of colistin resistance were 20.1% in 2017, 31.2% in 2018 and 26.9% in 2019. Conclusions CPKP diffusion is still an important issue despite the surveillance program. It is vital to enhance medical staff’s awareness on this because most CPKP first detections in SRS occurred during hospital stay due to a nosocomial acquisition with a comparable picture over time. Colistin resistance is increasing.

Published
2019

33. Role of pretreatment variables on plasma HIV RNA value at the sixth month of antiretroviral therapy including all first line drugs in HIV naïve patients: A path analysis approach

Author

Gaetano Maffongelli, Roberto Ferretto, Monica Basso, Elisabetta Schiaroli, Vinicio Manfrin, Saverio Giuseppe Parisi, Sandro Panese, Franco Baldelli, Samantha Andreis, Carlo Mengoli, Mario Cruciani, Renzo Scaggiante, Massimo Andreoni, Loredana Sarmati, Daniela Francisci, and Giorgio Palù

Subjects
RNA viruses, Male, 0301 basic medicine, Oncology, Genetics and Molecular Biology (all), Viral Diseases, Physiology, HIV Infections, Signal transduction, Pathology and Laboratory Medicine, Biochemistry, 0302 clinical medicine, Immunodeficiency Viruses, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, education.field_of_study, Multidisciplinary, Pharmaceutics, virus diseases, Middle Aged, Vaccination and Immunization, Body Fluids, Infectious Diseases, Blood, Treatment Outcome, Anti-Retroviral Agents, Medical Microbiology, Viral Pathogens, Viruses, Medicine, RNA, Viral, Regression Analysis, Female, Pathogens, Anatomy, Coreceptors, Algorithms, Research Article, Adult, Cart, Cell biology, medicine.medical_specialty, Genotype, Settore MED/17 - Malattie Infettive, Science, Immunology, 030106 microbiology, Population, Antiretroviral Therapy, Viremia, Microbiology, Blood Plasma, Virus, 03 medical and health sciences, Pharmacotherapy, Drug Therapy, Antiviral Therapy, Virology, Internal medicine, Retroviruses, HIV tropism, medicine, Humans, education, Microbial Pathogens, Tropism, business.industry, Lentivirus, Organisms, Biology and Life Sciences, HIV, CD coreceptors, medicine.disease, CD4 Lymphocyte Count, Viral Tropism, Chronic Disease, HIV-1, Tissue tropism, Preventive Medicine, business
Abstract

Background and aimsWe investigated the conditioning roles of viral tropism and other variables on plasma HIV RNA levels after 6 months of combination antiretroviral therapy (cART) in an HIV-infected Italian naïve population using regression tree, random forest regression, and path analysis (PA). Patients in this multicenter observational study were treated with all antiviral drugs that are currently recommended as first-line therapies.MethodsAdult patients with chronic HIV infection were enrolled at the beginning of first-line cART (T0). The main variables were age, gender, tropism, "lcd4_0" and "lcd4_6" (log10 CD4+counts at T0 and after 6 months of cART, respectively), and "lrna0" (log10 HIV RNA at T0). Regression tree and random forest analyses were applied. The predictive effect on lrna6 (log10-transformed plasma HIV RNA after 6 months of cART) was also investigated via PA (x4->lcd4_0->lrna0->lrna6) with a treatment selection step included as a dependent (mediator) variable for each third drug and, as predictive covariates, age, female, x4_10, x4_5, lcd4_0, and lrna0. Tropism was assessed in plasma using the Geno2pheno algorithm with 2 false positive rate (FPR) cut-offs: 5% (x4_5) and 10% (x4_10).ResultsThe study included 571 subjects (21% x4_10 and 10.7% x4_5). The only important predictor of lrna6 was lrna0, and a positive indirect effect of bearing X4 virus in plasma was suggested. A significant direct positive effect of protease inhibitors on lrna6 was found (p = 0.022), and a significant negative effect of integrase strand transfer inhibitor (INSTI) was also detected (p = 0.003 for FPR ≤ 5% and p = 0.01 for FPR < 10%). PA predicted mean residual viremias of 40 copies/mL without INSTI and 3 copies/mL with INSTI.ConclusionsPA indicated a possible indirect role of HIV tropism on lrna6 with both FPR < 10% and ≤ 5%. Patients treated with INSTI had a predicted residual viremia of 3 copies/mL.

Published
2019

34. Cytomegalovirus, Epstein-Barr virus and human herpesvirus 8 salivary shedding in HIV positive men who have sex with men with controlled and uncontrolled plasma HIV viremia: a 24-month longitudinal study

Author

Elisa Franchin, Claudia Del Vecchio, Saverio Giuseppe Parisi, Massimo Andreoni, Giorgio Palù, Daniela Zago, Carlo Mengoli, Renzo Scaggiante, Loredana Sarmati, Monica Basso, Maria Angela Biasolo, and Samantha Andreis

Subjects
Male, 0301 basic medicine, Herpesvirus 4, Human, Cytomegalovirus, HIV Infections, medicine.disease_cause, Men who have sex with men, Sexual and Gender Minorities, 0302 clinical medicine, Medicine, Longitudinal Studies, 030212 general & internal medicine, Longitudinal persistence of salivary shedding, CMV DNA, HHV-8 DNA, Coinfection, virus diseases, Herpesviridae Infections, Middle Aged, Viral Load, Virus Shedding, Exact test, Infectious Diseases, Cytomegalovirus Infections, Herpesvirus 8, Human, medicine.symptom, Viral load, Oncovirus, Research Article, Adult, Settore MED/17 - Malattie Infettive, Viremia, EBV DNA, Asymptomatic, Virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Humans, lcsh:RC109-216, Homosexuality, Male, Saliva, AIDS-Related Opportunistic Infections, business.industry, HIV positive MSM, medicine.disease, Virology, 030104 developmental biology, DNA, Viral, HIV-1, business
Abstract

Background This longitudinal study described Cytomegalovirus (CMV) DNA, Epstein-Barr (EBV) DNA and human herpesvirus 8 (HHV-8) DNA asymptomatic salivary shedding in HIV-positive men who have sex with men (MSM). We aimed to 1-analyze frequency and persistence of herpesvirus shedding, 2-correlate herpesvirus positivity and HIV viroimmunological parameters and 3-assess the association between HIV-RNA suppression and herpesvirus replication. Methods Herpesvirus DNA was tested with an in-house real-time PCR in 2 salivary samples obtained at T0 and T1 (24 months after T0). HIV-RNA was evaluated in the 24 months prior to T0 and in the 24 months prior to T1; MSM were classified as successfully suppressed patients (SSPs), viremic patients (VPs) and partially suppressed patients (PSPs). EBV DNA load was classified as low viral load (EBV-LVL, value ≤10,000 copies/ml) and as high viral load (EBV-HVL,> 10,000 copies/ml). Mann-Whitney U test tested the difference of the median between groups of patients. Chi-squared test and Fisher’s exact test compared categorical variables according to the frequencies. Kruskal-Wallis test compared continuous data distributions between levels of categorical variables. Results Ninety-two patients (median CD4+ count 575 cells/mm3, median nadir 330 CD4+ cells/mm3) were included: 40 SSPs,33 VPs and 19 PSPs. The more frequently single virus detected was EBV, both at T0 and at T1 (in 67.5 and 70% of SSPs, in 84.8 and 81.8% of VPs and in 68.4 and 73.7% of SPSs) and the most frequently multiple positivity detected was EBV + HHV-8. At T1, the percentage of CMV positivity was higher in VPs than in SSPs (36.4% vs 5%, p

Published
2018

35. 2506. Trends of Transmitted Resistance Mutations to Four Drug Classes, HIV-Subtypes And Herpesviruses Replication Among Subjects Recently Diagnosed as HIV Infected Over 2004–2019

Author

Ermenegildo Francavilla, Loredana Sarmati, Beatrice Parisatto, Massimo Andreoni, Roberto Ferretto, Daniela Zago, Sandro Panese, Mario Cruciani, Renzo Scaggiante, Camilla Stagni, Giorgio Palù, Federico Dal Bello, Monica Basso, Vinicio Manfrin, Saverio Giuseppe Parisi, and Irene Pozzetto

Subjects
Drug, business.industry, media_common.quotation_subject, Virology, Abstracts, Infectious Diseases, Oncology, Hiv infected, Poster Abstracts, Replication (statistics), Medicine, business, media_common, Hiv subtypes
Abstract

Background to evaluate circulation of drug resistance mutations (DRMs), sub-types (ST) and Herpesviruses replication among subjects recently diagnosed as HIV infected (pts) in Veneto (Italy), over 16 years, comparing previously reported trends with the most recent one, updated to 2019. Methods on plasma from 2919 patients diagnosed from July 2004 to April 2019, protease (PR), reverse transcriptase (RT) and recently Integrase (In) were analyzed for DRMs, susceptibility profile (Stanford db) and ST. Potential low-level resistances were excluded. CMV-DNA and EBV-DNA were evaluated by in-house Real-Time-PCR in PBMCs. Results in 5 periods (2004/06, 07/09, 10/12, 13/16, 17–19) 334, 796, 752, 750 and 287 patients were recruited; non-B-ST were 21.9, 29.3, 33, 32.7 and 48.1% (33.5% Italians in 17–19), respectively. A significant increase of non-B-ST (P < 0.0001 for trend) and of the percentage of Italians with non-B-strains (P = 0.029) were observed. Resistance to PR or to multiple classes declined but not to non-nucleoside RT inhibitors (NNRTI) (Fig 1). E138A alone, not included in the previous evaluations, increased from 2.3 to 1.8, to 3.2, to 3.6, to 4.7% in 2017-19. No primary TDRM to In-Inhibitors (InIn) were found in 469 B-ST-Pts enrolled in 2014–19; 16% had major TDRM for RT/PI. Among 231 non-B patients, 12,5% with other TDRMs, only a 143C and a 66I were found. Accessory InIn-TDRMs were detected (Figures 2 and 3). Nevertheless, from 2009 to 2019 in Veneto 114 InIn-failed and potentially transmitters patients with In-DRMs were found. In 2017–19 17,3% of patients had CMV-DNA in PBMCs, with a median CD4 of 55 (8%), HIV-RNA 247251 cps/mL and EBV-DNA of 811 cps/106 PBMCs (3% were neg); Patients CMV-DNA-negative (82,7%) had median CD4 of 334 (18,9%), HIV-RNA 47770 cps/mL and a significantly lower EBV-DNA of 194 cps/106 PBMCs (15% were neg): differences between immuvirological variables were significant. Conclusion An increase of non-B strains and a slight increase of TDRMs among B-ST were observed. The persistent circulation of NNRTI-DRMs, the shortage of major In-TDRMs but a circulation of many In-polymorphisms have implications on the screening at baseline and on the selection of the first-line HAART. Many patients with lower CD4 and higher HIV replication has an incomplete control of co-infecting herpesviruses, which contribute to immunoactivation. Disclosures All authors: No reported disclosures.

Published
2019
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36. Epstein-Barr and cytomegalovirus DNA salivary shedding correlate with long-term plasma HIV RNA detection in HIV-infected men who have sex with men

Author

Giorgio Palù, Renzo Scaggiante, Loredana Sarmati, Elisa Franchin, Carlo Mengoli, Carlo Torti, Monica Basso, Marzia Franzetti, Saverio Giuseppe Parisi, Mario Cruciani, Samantha Andreis, and Claudia Del Vecchio

Subjects
0301 basic medicine, Saliva, business.industry, Congenital cytomegalovirus infection, medicine.disease, Virology, Virus, Men who have sex with men, Cytomegalovirus DNA, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Infectious Diseases, Epstein barr, Hiv infected, Immunology, Medicine, 030212 general & internal medicine, business, Viral load
Abstract

The aim of the study was to evaluate cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA salivary shedding in HIV-positive men who have sex with men (MSM) and to determine whether viro-immunological parameters and long-term (24 months) plasma HIV RNA (pHIV) detection may predict herpesviruses replication. A total of 193 HIV-positive MSM were consecutively recruited (mean CD4+ cell count 607 cells/mm(3) and mean nadir value 333 cells/mm(3) ); pHIV was analyzed for 24 months prior to saliva sampling: patients were categorized as successfully suppressed (SS) and not suppressed (NS). The EBV viral load was categorized as high viral load (HVL), intermediate (IVL), or low (LVL), CMV DNA as positive or negative. NS patients experienced both herpesviruses detectability more frequently respect to SS patients (P = 0.034); conversely, no salivary shedding was more frequent in SS patients (P = 0.014). HVL EBV was more frequent in NS patients than in SS subjects (P = 0.038 for isolated EBV detection and P = 0.001 when CMV shedding was associated). NS subjects with HVL EBV had a median pHIV of 43,820 copies/ml, significantly higher respect to IVL and LVL patients (P = 0.027 and P = 0.0005, respectively). CMV shedding was mostly associated to EBV shedding. NS patients showed a significantly higher frequency of saliva HVL EBV detection compared to SS patients; moreover, NS patients with HVL EBV had a higher pHIV respect to those with IVL and LVL shedding. Our results suggest that a successful pHIV suppression could reduce the burden of salivary EBV replication and likely the risk of herpesviruses-related cancers.

Published
2015
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37. Soluble CD163 and soluble CD14 plasma levels but not cellular HIV-DNA decrease during successful interferon-free anti-HCV therapy in HIV-1–HCV co-infected patients on effective combined anti-HIV treatment

Author

Giorgio Palù, Anna Maria Cattelan, Samantha Andreis, Saverio Giuseppe Parisi, Nicola Menegotto, Monica Basso, Silvia Cavinato, Renzo Scaggiante, Carlo Mengoli, and Massimo Andreoni

Subjects
0301 basic medicine, Male, HIV-1â HCV coinfection, Human immunodeficiency virus (HIV), Lipopolysaccharide Receptors, HIV Infections, Cellular HIV-DNA, Direct-acting antivirals, HIV-1–HCV coinfection, sCD14, sCD163, Immunology and Allergy, Immunology, Microbiology (medical), medicine.disease_cause, 0302 clinical medicine, Medical microbiology, HIV-1–HCV coinfection, Adult, Aged, Aged, 80 and over, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Antiviral Agents, Coinfection, DNA, Viral, Female, Hepatitis C, Chronic, Humans, Middle Aged, Receptors, Cell Surface, Retrospective Studies, Young Adult, Receptors, 80 and over, Medicine, Soluble cd163, Viral, 030212 general & internal medicine, Chronic, virus diseases, General Medicine, Hepatitis C, CD, Differentiation, Cell Surface, Cohort, medicine.symptom, medicine.medical_specialty, Settore MED/17 - Malattie Infettive, CD14, Inflammation, 03 medical and health sciences, Antigens, business.industry, Interferon free, Myelomonocytic, DNA, Plasma levels, 030104 developmental biology, business
Abstract

Soluble CD163, soluble CD14 and cellular HIV-1-DNA levels reflect two different aspects of HIV infection: immune activation and the reservoir of infected cells. The aim of this study was to describe their relationships in a cohort of HIV–HCV co-infected patients successfully treated for both HCV and HIV infections. Fifty-five patients were recruited and studied prior to the start of direct-acting antivirals (DAAs) (T0), at week 12 of DAA treatment (T1) and 24 weeks after T0 (T2). The subjects were classified as having undetectable plasma HIV viraemia (UV) or low-level viraemia (LLV) in the 18 months before T2. Plasma levels of sCD163 and of sCD14 were comparable in patients with UV and in subjects with LVL at T0, T1 and T2. The HIV DNA level was positively correlated with LLV but not with sCD163 and sCD14 levels; these two markers of inflammation were positively correlated (p = 0.017). Soluble CD163 and sCD14 decreased over time from T0 to T2 (p = 0.000 and p = 0.034, respectively). In conclusion, the significant decrease in sCD163 and sCD14 levels in patients cured of HCV infection, regardless of the presence of LLV, suggests a main role for HCV in immune activation in HIV–HCV co-infected patients.

Published
2018

38. Time course of cellular HIV-DNA and low-level HIV viremia in HIV-HCV co-infected patients whose HCV infection had been successfully treated with directly acting antivirals

Author

Anna Maria Cattelan, Monica Basso, Giorgio Palù, Silvia Cavinato, Renzo Scaggiante, Marzia Franzetti, Samantha Andreis, Saverio Giuseppe Parisi, and Massimo Andreoni

Subjects
0301 basic medicine, Male, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Gastroenterology, Medical microbiology, Immunology and Allergy, Longitudinal Studies, Low-level viremia, Aged, 80 and over, Cellular HIV-DNA, Hepatitis C virus, Human immunodeficiency virus, Longitudinal study, Immunology, Microbiology (medical), virus diseases, General Medicine, Middle Aged, Viral Load, Treatment Outcome, Female, Adult, medicine.medical_specialty, Settore MED/17 - Malattie Infettive, 030106 microbiology, Viremia, Peripheral blood mononuclear cell, Antiviral Agents, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, In patient, Aged, business.industry, Hepatitis C, Chronic, medicine.disease, 030104 developmental biology, Time course, DNA, Viral, Hcv treatment, Leukocytes, Mononuclear, business
Abstract

This longitudinal study described cellular HIV-DNA changes and their correlation with HIV low-level plasma viremia (LLV) in HIV-HCV co-infected patients on successful antiretroviral and anti-HCV therapy by treatment with direct-acting antivirals (DAA). Thirty-nine patients were examined prior to the start of DAA (T0), after week 12 (T1) and 24 weeks (T2) of anti-HCV therapy. Cellular PBMC HIV-DNA was analysed as an absolute value and as the percentage of increase or decrease from T0 to T2. Patients were classified as having undetectable plasma HIV viraemia (UV) or LLV in the year before the start of anti-HCV treatment and within the T0-T2 study period. Thirty-five patients (89.7%) of the 39 subjects enrolled had the same plasma HIV viraemia control in the year before HCV treatment and in the T0-T2 interval. The HIV-DNA value at T0 and at T2 was higher in patients with LLV than in subjects with UV (p = 0.015 and p = 0.014, respectively). A similar proportion of patients with LLV and UV experienced an increase or decrease of HIV-DNA from T0 to T2. The percentage increase in HIV-DNA value (262.8%) from T0 to T2 was higher compared to the decrease (43.5%) in patients with UV (p = 0.012), and it was higher compared to the percentage increase in HIV-DNA value reported in subjects with LLV (262.8 versus 49%, p = 0.026). HIV-HCV co-infected patients experienced a multifaceted perturbation of cellular HIV-DNA levels within a 24-week period during anti-HCV treatment; the extent of the phenomenon was greater in subjects with UV. Fast HCV-RNA clearance seemed to have a greater influence on the cellular reservoir than on plasma HIV-RNA.

Published
2017

39. Prevalence, molecular epidemiology and intra-hospital acquisition of Klebsiella pneumoniae strains producing carbapenemases in an Italian teaching hospital from January 2015 to September 2016

Author

Anna Maria Ferrari, Nicola Menegotto, Monica Basso, Ettore De Canale, Renzo Scaggiante, Saverio Giuseppe Parisi, Andrea Bartolini, Stefania Stefani, Samantha Andreis, Elisa Franchin, and Giorgio Palù

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, carbapenemases, Klebsiella pneumoniae, 030106 microbiology, Microbial Sensitivity Tests, Real-Time Polymerase Chain Reaction, beta-Lactamases, lcsh:Infectious and parasitic diseases, Teaching hospital, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Internal medicine, Intensive care, parasitic diseases, Prevalence, medicine, Humans, lcsh:RC109-216, colistin, 030212 general & internal medicine, Tertiary level, Hospitals, Teaching, Cross Infection, Molecular Epidemiology, longitudinal survey, biology, Molecular epidemiology, business.industry, General Medicine, biology.organism_classification, Klebsiella Infections, Surgery, Infectious Diseases, Italy, Colistin, Multilocus sequence typing, Female, Rectal swab, business, Multilocus Sequence Typing, medicine.drug
Abstract

Objectives We described Klebsiella pneumoniae producing carbapenemase (CPKP) spread from 01/01/2015 to 13/09/16 in a tertiary level hospital. Methods The first positive surveillance rectal swab (SRS) or clinical sample (CS) collected in the medical department (MD), surgical department (SD) and intensive care department (ICD) were included in the study. A validated in-house Real-Time PCR method was used to detect carbapenemases; multilocus sequence typing (MLST) was used for further characterization of the strains. Results 21535 patients were included: 213 CPKP strains from surveillance rectal swab (SRS) and 98 from clinical samples (CS) were collected. The percentage of CPKP detected in SRS with respect to CS increased in the medical MD from 2015 to 2016 (p=0.01) and in ICD from 2012 to 2015 (p=0.0001), while it decreased in SD from 2014 to 2016 (p=0.003); 68.5% of the positive SRS had a previous negative SRS; CPKP was more frequently identified in CS than in SRS in MD. Twelve strains harboured more than one carbapenemase gene. Many other species harbouring a carbapenemase gene were collected. Conclusions MDs need more inclusive surveillance criteria. The late detection of positive SRS underlined the risk of colonization during hospitalization.

Published
2017

40. Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy

Author

Davide Leoni, Loredana Sarmati, Samantha Andreis, Oliviero Bosco, Roberto Ferretto, Gaetano Maffongelli, Renzo Scaggiante, Mario Cruciani, Carlo Torti, Giorgio Palù, Saverio Giuseppe Parisi, Carlo Mengoli, Monica Basso, and Massimo Andreoni

Subjects
0301 basic medicine, Microbiology (medical), Cart, Adult, Male, Genotype, Genotyping Techniques, Sustained Virologic Response, Settore MED/17 - Malattie Infettive, 030106 microbiology, Viremia, HIV Infections, Biology, Virus, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Tropism, Pharmacology, virus diseases, Middle Aged, medicine.disease, Viral Tropism, Infectious Diseases, Treatment Outcome, Anti-Retroviral Agents, Cohort, Immunology, Tissue tropism, HIV-1, RNA, Viral, Female, False positive rate, Viral load
Abstract

OBJECTIVES To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. PATIENTS AND METHODS Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach. RESULTS A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log10 HIV RNA at T0 on log10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log10 HIV RNA at T0 (P = 0.003) was apparent. CONCLUSIONS PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy.

Published
2017

41. Nevirapine use, prolonged antiretroviral therapy and high CD4 nadir values are strongly correlated with undetectable HIV-DNA and -RNA levels and CD4 cell gain

Author

Andrea Galgani, Magdalena Viscione, Marco Montano, Loredana Sarmati, Stefano Boros, Carolina Andreoni, A. Ricciardi, Saverio Giuseppe Parisi, Giorgio Palù, Renzo Scaggiante, Samantha Andreis, Massimo Andreoni, and Gaetano Maffongelli

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, Multivariate analysis, Nevirapine, Settore MED/17 - Malattie Infettive, Anti-HIV Agents, Population, HIV Infections, Viremia, Treatment goals, Biology, Gastroenterology, Antiretroviral Therapy, Highly Active, Internal medicine, medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), education, Pharmacology, education.field_of_study, RNA, Middle Aged, Viral Load, medicine.disease, Antiretroviral therapy, United States, CD4 Lymphocyte Count, Cross-Sectional Studies, Treatment Outcome, Infectious Diseases, DNA, Viral, Immunology, RNA, Viral, Female, Nadir (topography), medicine.drug
Abstract

To evaluate the correlations of the combination of undetectable HIV-DNA (10 copies/10(6) peripheral blood mononuclear cells) and HIV-RNA (1 copy/mL of plasma) levels and a CD4 cell count of500 cells/mm(3) (defined as the treatment goal) in a group of 420 antiretroviral treatment (ART) responder patients.A cross-sectional, open-label, multicentre trial was conducted in a cohort of 420 HIV-infected ART-treated subjects with viral loads persistently50 copies/mL for a median observation time of 28.8 months. HIV-DNA and residual viraemia values and demographic, virological and immunological data were collected for each subject.Undetectable HIV-DNA was found in 16.6% (70/420) of patients and was significantly correlated with undetectable (1 copy/mL) plasma viraemia (P = 0.0001). Higher CD4 cell count nadir (P 0.001), a lower HIV-RNA viraemia at the start of treatment (P = 0.0016) and nevirapine use (P 0.001) were correlated with an undetectable value of HIV-RNA. Twenty-six out of 420 patients (6.2%) reached the treatment goal. In multivariate analysis, higher nadir CD4 cell count (OR 3.86, 95% CI 1.47-10.16, P = 0.006), the duration of therapy (OR 1.07, 95% CI 1.02-1.12, P = 0.004) and the use of nevirapine (OR 2.59, 95% CI 1.07-6.28, P = 0.034) were independently related to this condition.Only 6.2% of ART-responder patients presented the combination of three laboratory markers that identified them as full responders. These results indicate the high variability of the ART-responding population and lead us to suggest caution in the selection of patients for possible simplification regimens.

Published
2012
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42. Baseline Cellular HIV DNA Load Predicts HIV DNA Decline and Residual HIV Plasma Levels during Effective Antiretroviral Therapy

Author

Caterina Boldrin, Giorgio Palù, Renzo Scaggiante, Monica Basso, Roberto Ferretto, Samantha Andreis, Saverio Giuseppe Parisi, Loredana Sarmati, Carlo Mengoli, Massimo Andreoni, Mario Giobbia, Vinicio Manfrin, and Mario Cruciani

Subjects
Adult, Male, Microbiology (medical), Settore MED/17 - Malattie Infettive, Anti-HIV Agents, Human immunodeficiency virus (HIV), HIV Infections, Viremia, Biology, medicine.disease_cause, Plasma, chemistry.chemical_compound, Antiretroviral Therapy, Highly Active, Virology, medicine, Humans, Aged, Transmission (medicine), virus diseases, RNA, Middle Aged, Viral Load, medicine.disease, Antiretroviral therapy, CD4 Lymphocyte Count, Blood, chemistry, DNA, Viral, Immunology, Cohort, HIV-1, RNA, Viral, Female, Drug Monitoring, Viral load, DNA
Abstract

Cellular human immunodeficiency virus type 1 (HIV-1) DNA may be considered a marker of disease progression with significant predictive power, but published data on its correlation with plasma HIV RNA levels and CD4 counts in acute and chronic patients are not conclusive. We evaluated a cohort of 180 patients naïve for antiretroviral therapy before the beginning of treatment and after a virological response in order to define the indicators correlated with HIV DNA load decrease until undetectability. The following variables were evaluated as continuous variables: age, CD4 cell count and log 10 HIV DNA level at baseline and follow-up, and baseline log 10 HIV RNA level. Primary HIV infection at the start of therapy, an HIV RNA level at follow-up of

Published
2012
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43. Daclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin

Author

Arianna Loregian, Saverio Giuseppe Parisi, Monica Basso, Lorenzo Messa, Giulio Nannetti, Silvia Cavinato, Renzo Scaggiante, Federico Dal Bello, Giorgio Palù, Samantha Andreis, and Anna Maria Cattelan

Subjects
0301 basic medicine, Liver Cirrhosis, Male, Cirrhosis, Pyrrolidines, Sofosbuvir, HIV Infections, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Medicine, media_common, education.field_of_study, medicine.diagnostic_test, Coinfection, Daclatasvir, HIV–HCV patients, Mutation, Population-based sequencing, Therapeutic drug monitoring, Virological failure, Microbiology (medical), Infectious Diseases, Imidazoles, Valine, General Medicine, Middle Aged, Hepatitis C, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, medicine.drug, Drug, medicine.medical_specialty, media_common.quotation_subject, Hepatitis C virus, 030106 microbiology, Population, Antiviral Agents, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Internal medicine, Drug Resistance, Viral, Ribavirin, Humans, lcsh:RC109-216, education, business.industry, medicine.disease, Virology, chemistry, Carbamates, business
Abstract

Objectives:\ud Effective treatment with direct-acting antiviral drugs against hepatitis C virus (HCV) is a medical need in cirrhotic HIV–HCV co-infected patients.\ud \ud Methods:\ud This study investigated the plasma levels of daclatasvir (DCV) and ribavirin (RBV) in HIV–HCV co-infected subjects treated with DCV, sofosbuvir, and RBV. Drug concentrations were quantified using validated high-performance liquid chromatography methods with ultraviolet detection. The HCV non-structural protein 5A and non-structural protein 5B coding regions were analyzed by population-based sequencing.\ud \ud Results:\ud DCV was dosed at week 4 and at week 8 of treatment, and RBV at week 8. One patient had the lowest DCV level, corresponding to 32.7% of the overall median value of the other patients at week 4 and about 40% at week 8. The Y93H variant was detected in this subject at weeks 8, 16, and 20 of treatment, but not before treatment or at day 2, and the patient experienced virological failure. Another subject with the Y93H variant at baseline and appropriate DCV levels had HCV RNA

Published
2016

44. Estimating minimum adult HIV prevalence: A cross-sectional study to assess the characteristics of people living with HIV in Italy

Author

Margherita Busso, Tullio Prestileo, Ermenegildo Francavilla, Marco Anselmo, Francesco Montella, Evangelista Sagnelli, Teresa Santantonio, Massimo Galli, Marcello Saitta, Giuseppe Foti, Cecilia Guariglia, Franco Baldelli, Simona Di Gianbenedetto, Pierluigi Viale, Francesco Castelli, Antonella d'Arminio Monforte, Angelo Pan, Gabriella D’Ettore, Maria Dorrucci, Salvatore Bruno, Tiziana Quirino, Mariangela Raimondo, Alessandro Bartoloni, Vinicio Manfrin, Giovanni Mazzarello, Eugenio Mantia, Raffaele Pempinello, Antonio Traverso, Barbara Suligoi, Fabio Bulla, Pietro Mesina, Alessia Zoncada, Gianfranco Orofino, Oliviero Bosco, Gianmichele Moise, Angelo Salomone Megna, Roberto Ferretto, Mauro Valle, Manuela Colafigli, Claudio Paternoster, S. Artioli, Giovanni Riccio, Stefania Bernardi, Paolo Grossi, Milena Zoppi, Sebastiano Maiuzzo, Giorgio Perboni, Sauro Tini, Giuseppe Ferrea, Nicoletta Ladisa, Enzo M. Farinella, Daniela Francisci, Dino Sgarabotto, Roberto Monarca, Enzo Petrelli, A. Franco, Izzo Cm, Pietro Bellissima, Francesco Ortu, Laura Sighinolfi, Antonio Chirianni, Filippo Bartalesi, Giulio De Stefano, Claudia Colomba, Laura Camoni, Salvatore Galvagna, Benedetto Maurizio Celesia, Andrea Petrucci, Camillo Baretti, Pierluigi Brugnaro, Federica Poletti, Maurilio Chimenti, Camilla Ajassa, Mario Falciano, Rosaria La Sala, Sauro Luchi, V. Portelli, Annamaria Degli Antoni, Francesco Mazzotta, Giuliano Zuccati, Vincenzo Colangeli, Ercole Concia, Giordano Madeddu, Maria Cristina Salfa, Francesca Cattelan, Nicola Acone, Vincenza Regine, Olivia Bargiacchi, Maurizio de Martino, F. Paoletti, Giovanni Cassola, Giuliano Schettino, Carlo De Stefano, Enza Anzalone, D. Aquilini, Giacomo Magnani, Vanni Borghi, Roberta Gastaldi, Alessandra Govoni, Cristina Rossi, Rita Consolini, Gioacchino Angarano, Gloria Taliani, Tommaso Fontana, Sergio Lo Caputo, Davide Vitullo, Pierpaolo Congedo, Emanuela Vaccher, Paolo Viganò, Maria Stella Mura, Claudio Cancellieri, Enrico Girardi, Francesca Savalli, Cecilia Fico, Anna Maria Cattelan, Alessandro Chiodera, Renzo Scaggiante, P. Osimani, Caterina Bramato, Nicola Pietrosillo, Giovanna D'Alessio, Salvatore Bonfante, Vincenzo Vullo, Andrea Gori, Margherita Dalessandro, Domenico Lucchino, Massimo Deseraca, Paolo Tundo, Alfredo Pennica, M. Paoloni, Antonella Castagna, Nicola Serrao, Paolo Costa, Franco Marranconi, Massimo Villa, Pietro Filippini, Maurizio Setti, Eligio Pizzigallo, Marco Tinelli, Mauro Marchili, Domenico Santoro, Cesira Nencioni, Piera Dones, Vincenzo Renda, Alberto Giannetti, Domenico La Rovere, Nicoletta Dorigoni, Guido Palamara, Angelo Iodice, Clara Gabiano, Peter Mian, Luigi Guarnieri, Andrea De Luca, Nicola Tripodi, Giovanni Cristina, Giustino Parruti, Maria Montroni, Loredana Palvarini, Marco Rizzi, Benvenuto Grisorio, Corrado Catalani, Paolo Emilio Manconi, Jacopo Vecchiett, Tiziana Carli, Riccardo Iapoce, Massimo Andreoni, Adriano Lazzarin, Giorgetta Casalino Finocchio, D Sacchini, Mario Gobber, Spartaco Sani, Marco Campus, Rosario La Rosa, Maurizio Mazzeo, Stefano Bonora, Michele Trezzi, Paolo Bassi, Angela La Gala, Alessandro Grimaldi, Dante Di Giammartino, Guido Leo, Gaetano Filice, Antonio Salvo, Paolo Bonfanti, Chiara Pasqualini, Marcello Tavio, Luca Butini, N. Abrescia, Angela Linzalone, Gianpaolo Natalini Ramponi, Pierangelo Rovere, Piero Cortese, Dario Bartolozzi, F. Resta, Miriam Lichtner, Loredana Sarmati, Francesco Cesario, Renato F. Frongillo, Ivano Mezzaroma, Carlo Ferrari, Lorenzo Minoli, Paola Di Stefano, Lucina Titone, Rosa Boncoraglio, Mariana Farenga, Giuliano Rizzardini, Stefano Aviani Barbacci, Andrea Giacometti, Andrea Antinori, Antonio Caterini, Consuelo Geraci, Piergiorgio Chiriacò, Lucio Cosco, Claudio Viscoli, Alfredo Scalzini, Sandro Piga, Massimo Arlotti, Cecilia Occhino, Roberto Luzzati, Paola Sabbatini, Guglielmo Borgia, Umberto Tirelli, Antonio Davi, Letizia Cristiano, Cristina Mussini, Roberto Cauda, Patrizio Vittucci, B. Salassa, Marco Libanore, Maria Pina Sciotti, Isa Picerno, Matteo Bassetti, Benedetto Caroleo, Oswald Moling, Danilo Tacconi, Massimo Puoti, Camoni, Laura, Raimondo, Mariangela, Dorrucci, Maria, Regine V, Salfa MC, CARPHA Study, Group, Lazzarin, Adriano, Castagna, Antonella, Camoni, L, Raimondo, M, Dorrucci, M, Regine, V, Salfa, M, Suligoi, B, Di Giammartino, D, Parruti, G, Di Stefano, P, Paoloni, M, D'Alessandro, M, Grimaldi, A, Sciotti, M, Pizzigallo, E, Vecchiett, J, De Stefano, C, La Gala, A, De Stefano, G, Linzalone, A, Cesario, F, Cosco, L, Caroleo, B, Foti, G, Serrao, N, Lucchino, D, Chirianni, A, Abrescia, N, Pempinello, R, Izzo, C, Borgia, G, Filippini, P, Sagnelli, E, Iodice, A, Megna, A, D'Alessio, G, Acone, N, Mazzeo, M, Sacchini, D, Ferrari, C, Degli Antoni, A, Magnani, G, Mussini, C, Borghi, V, Viale, P, Colangeli, V, Sighinolfi, L, Libanore, M, Govoni, A, Cancellieri, C, Bassi, P, Arlotti, M, Luzzati, R, Bassetti, M, Tirelli, U, Vaccher, E, Moise, G, Palamara, G, Bernardi, S, Falciano, M, Vullo, V, D'Ettore, G, Renda, V, Guariglia, C, Taliani, G, Mezzaroma, I, Paoletti, F, Ajassa, C, Gastaldi, R, Andreoni, M, Sarmati, L, Montella, F, Antinori, A, Giannetti, A, Pietrosillo, N, Girardi, E, Pennica, A, Cauda, R, Colafigli, M, Di Gianbenedetto, S, Caterini, A, Monarca, R, Barbacci, S, Ramponi, G, Marchili, M, Anzalone, E, Lichtner, M, Ferrea, G, Cassola, G, Viscoli, C, Mazzarello, G, Setti, M, Artioli, S, Riccio, G, Finocchio, G, Anselmo, M, Rizzi, M, Scalzini, A, Castelli, F, Quirino, T, Santoro, D, Pan, A, Zoncada, A, Bonfanti, P, Viganò, P, Villa, M, Tinelli, M, Perboni, G, Palvarini, L, Costa, P, Puoti, M, Galli, M, Rizzardini, G, Monforte, A, Lazzarin, A, Castagna, A, Gori, A, Minoli, L, Filice, G, Grossi, P, Giacometti, A, Tavio, M, Montroni, M, Butini, L, Osimani, P, Petrelli, E, Chiodera, A, Vittucci, P, Sabbatini, P, Pasqualini, C, Valle, M, Zoppi, M, Mantia, E, Schettino, G, Deseraca, M, Vitullo, D, Bargiacchi, O, Orofino, G, Bramato, C, Busso, M, Salassa, B, Farenga, M, Bonora, S, Leo, G, Poletti, F, Gobber, M, Cristina, G, Gabiano, C, Mian, P, Moling, O, Paternoster, C, Dorigoni, N, Fontana, T, Angarano, G, Ladisa, N, La Rovere, D, Fico, C, Bulla, F, Santantonio, T, Grisorio, B, Chiriacò, P, Congedo, P, Tundo, P, Resta, F, Cristiano, L, Mura, M, Madeddu, G, Mesina, P, Piga, S, Campus, M, Manconi, P, Ortu, F, Salvo, A, Baretti, C, La Sala, R, Bellissima, P, Bonfante, S, Galvagna, S, Celesia, B, La Rosa, R, Maiuzzo, S, Guarnieri, L, Bruno, S, Picerno, I, Tripodi, N, Farinella, E, Occhino, C, Titone, L, Colomba, C, Prestileo, T, Saitta, M, Dones, P, Boncoraglio, R, Davi, A, Franco, A, Portelli, V, Savalli, F, Geraci, C, Chimenti, M, Luchi, S, Catalani, C, Trezzi, M, Aquilini, D, Sani, S, Nencioni, C, Carli, T, Mazzotta, F, Lo Caputo, S, Zuccati, G, Iapoce, R, Consolini, R, Bartolozzi, D, Bartoloni, A, Bartalesi, F, DE LUCA, A, De Martino, M, Tacconi, D, Tini, S, Baldelli, F, Francisci, D, Frongillo, R, Traverso, A, Francavilla, E, Ferretto, R, Marranconi, F, Manfrin, V, Cortese, P, Rossi, C, Cattelan, F, Petrucci, A, Brugnaro, P, Sgarabotto, D, Scaggiante, R, Cattelan, A, Bosco, O, Concia, E, Rovere, P, Regine, Vincenza, Salfa, Maria Cristina, Suligoi, Barbara, and Luzzati, Roberto

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Immunology, Infectious Diseases, Virology, Settore MED/17 - Malattie Infettive, Epidemiology, Cross-sectional study, Human immunodeficiency virus (HIV), MEDLINE, HIV Infections, medicine.disease_cause, Anti-Retroviral Agents, CD4 Lymphocyte Count, Cross-Sectional Studies, Female, Humans, Italy, Middle Aged, Prevalence, Retrospective Studies, medicine, HIV Infection, HIV, prevalence, Italy, Cross-Sectional Studie, business.industry, Transmission (medicine), HIV, Retrospective cohort study, Hiv prevalence, Northern italy, Anti-Retroviral Agent, business, Viral load, Human, Demography
Abstract

In 2012, we conducted a retrospective cross-sectional study to assess the number of people living with HIV linked to care and, among these, the number of people on antiretroviral therapy. The health authority in each of the 20 Italian Regions provided the list of Public Infectious Diseases Clinics providing antiretroviral therapy and monitoring people with HIV infection. We asked every Public Infectious Diseases Clinic to report the number of HIV-positive people diagnosed and linked to care and the number of those on antiretroviral therapy during 2012. In 2012, 94,146 people diagnosed with HIV and linked to care were reported. The majority were males (70.1%), Italians (84.4%), and aged between 25 and 49 years (63.4%); the probable route of transmission was heterosexual contact in 37.5% of cases, injecting drug use in 28.1%, and male-to-male contact in 27.9%. Among people in care, 20.1% had less than 350 CD4 cells/μl, 87.6% received antiretroviral therapy, and among these, 62.4% had a CD4 cell count higher than 350 cells/μl. The overall estimated prevalence of individuals diagnosed and linked to care in 2012 in Italy was 0.16 per 100 residents (all ages). Adding the estimated proportion of undiagnosed people, the estimated HIV prevalence would range between 0.19 and 0.26 per 100 residents. In Italy, the majority of people diagnosed and linked to care receive antiretroviral therapy. A higher prevalence of individuals diagnosed and linked to care was observed in Northern Italy and among males. More information for developing the HIV care continuum is necessary to improve the entire engagement in care, focusing on test-and-treat strategies to substantially reduce the proportion of people still undiagnosed or with a detectable viral load.

Published
2015

45. Structural-equation-modelling of the tropism impact on achieving viral suppression within six months in naïve HIV patients

Author

Monica Basso, D. Leone, Mario Cruciani, Renzo Scaggiante, Oliviero Bosco, Carlo Mengoli, Samantha Andreis, Massimo Andreoni, Loredana Sarmati, Giorgio Palù, Saverio Giuseppe Parisi, Gaetano Maffongelli, and Roberto Ferretto

Subjects
Oncology, medicine.medical_specialty, Efavirenz, Nevirapine, Settore MED/17 - Malattie Infettive, business.industry, Public Health, Environmental and Occupational Health, Lamivudine, virus diseases, Lopinavir, Atazanavir, chemistry.chemical_compound, Infectious Diseases, Poster Sessions – Abstract P147, chemistry, Abacavir, Internal medicine, Immunology, medicine, Tissue tropism, business, Tropism, medicine.drug
Abstract

Introduction : Aim of the study was to evaluate the relevance of baseline (BL) plasma tropism of HIV on the achievement of a viral suppression within six months of antiviral therapy (ARV) in naive patients by a structural-equation-modelling. Materials and Methods : Two-hundred and twenty-seven patients were enrolled; viral tropism on plasma was determined at baseline (BL) by sequencing and interpretation by genotopheno algorithm. Booster atazanavir or lopinavir, or efavirenz or nevirapine were used, in combination with either abacavir/lamivudine or tenofovir-emtricitabine. Results : X4-tropism correlate negatively with CD4 cell count at BL and follow-up (FU), and CD4 correlate negatively with BL-plasma viremia (PLV). BL-PLV correlate positively with FU-PLV. We have developed the hypothesis that the variables BL-CD4 and BL-PLV represent a mediators chain among X4-tropism and outcome of plasma viraemia at six months. This model, after structural-equation-modelling (SEM, Stata13), is shown in Figure 1. The indirect effect of X4-tropism on Fup-PLV is significant (p

Published
2014

46. Decreasing trends of drug resistance and increase of non-B subtypes amongst subjects recently diagnosed as HIV-infected over the period 2004–2012 in the Veneto Region, Italy

Author

Vinicio Manfrin, Caterina Boldrin, Sandro Panese, Roberto Ferretto, Renzo Scaggiante, Mario Cruciani, Ermenegildo Francavilla, Monica Basso, Maria Cristina Rossi, Massimo Andreoni, Samantha Andreis, Saverio Giuseppe Parisi, Carlo Mengoli, Federico Dal Bello, and Giorgio Palù

Subjects
Microbiology (medical), Change over time, medicine.medical_specialty, business.industry, Immunology, Human immunodeficiency virus (HIV), Drug resistance, medicine.disease_cause, Microbiology, Chronic infection, Internal medicine, Hiv infected, Epidemiology, medicine, Genotypic resistance, Immunology and Allergy, Protease inhibitor (pharmacology), business
Abstract

The present study was designed to prospectively monitor transmitted drug resistance mutations (TDRMs) in the Veneto Region, Italy. Genotypic resistance testing was conducted on the plasma of 1882 patients consecutively enrolled at the time of diagnosis of human immunodeficiency virus (HIV) infection from 2004 to 2012. TDRMs were defined according to the Stanford HIV database algorithm. In total, 214 (16.1%) B subtype-infected and 58 (10.5%) non-B subtype-infected individuals were identified as having a primary or recent HIV-1 infection. In subtype B-infected subjects in 2004–2006, the prevalence of TDRMs was 20.0% in chronic infections and 25.5% in recent infections; in 2007–2009 the rates were 11.5% and 5.3%, respectively; and in 2010–2012 they were 11.3% and 15.2%, respectively. In non-B subtype-infected subjects in 2004–2006, the prevalence of TDRMs was 18.0% in chronic infections and 16.5% in recent infections; in 2007–2009 the rates were 5.7% and 0%, respectively; and in 2010–2012 they were 6.2% and 8.7%, respectively. Protease inhibitor resistance and combined resistance to two or three classes of drugs declined during the three study periods. The observed decrease in TDRMs and a simplification of the resistance patterns may reflect a change over time in the characteristics of the infecting subjects who are often unaware of their infection and transmit a wild-type strain.

Published
2013

47. Long-term therapy with nevirapine and tropism

Author

Monica Basso, J Monticelli, Giorgio Palù, Nicola Menegotto, Samantha Andreis, Stefano Nicolè, Silvia Bressan, O Moling, Massimo Andreoni, Saverio Giuseppe Parisi, and Renzo Scaggiante

Subjects
medicine.medical_specialty, education.field_of_study, Nevirapine, business.industry, Population, Public Health, Environmental and Occupational Health, virus diseases, Lamivudine, Single Center, Raltegravir, Emtricitabine, Virology, Gastroenterology, Infectious Diseases, Abacavir, Internal medicine, medicine, education, business, Tropism, medicine.drug
Abstract

Objective : A more potent effect on the residual viraemia was ascribed to nevirapine (NVP) with respect to other antiretroviral drugs; moreover a selection of X4 strains was described in patients (pts) with undetectable viraemia; our aim was to study viro-immunological parameters and tropism for co-receptor in pts on a long term successful therapy with NVP. Methods :14 pts on HAART from 130 months (GL, median value, range 118-156 months) without occurrence of blips, as assessable with the available methods at that time, were retrospectively selected from a single center cohort (Bolzano). Tropism for V3 was determined by population sequencing on blood, and using geno2pheno algorithm; cellular HIV DNA load was analysed by in-house Real-Time. A further eighteen months (mo) follow up was then observed. Data were compared with those obtained from a control group of 50 naive pts (GS), evaluated after a 36-mo successful therapy (median, range 12-84) with various drug combinations, with median baseline (BL) CD4 of 50/μl, comparable value with the GL cohort. Results : In 7 pts a R5-tropic (GLR5, FPR median 84.8%) and in 7 an X4-tropic strain (GLX4, FPR median 1.1%) was demonstrated. BL data of GLR5 were 46 y old, CD4 54/μl, HIV-RNA 104,000 cps/ml; HAART from 142 mo, with NVP from 125 (one after 70 mo on NVP switched to protease from 57); at follow up CD4 were 679/μl, HIV-DNA 60 cps/106 PBMCs (range

Published
2012

48. HIV coreceptor tropism in paired plasma, peripheral blood mononuclear cell, and cerebrospinal fluid isolates from antiretroviral-naïve subjects

Author

Giorgio Palù, Samantha Andreis, Mario Cruciani, Carlo Mengoli, Gabriella d'Ettorre, Saverio Giuseppe Parisi, Vincenzo Vullo, Oliviero Bosco, Renzo Scaggiante, Vinicio Manfrin, A. R. Buonomini, Massimo Andreoni, Loredana Sarmati, Carolina Andreoni, and Caterina Boldrin

Subjects
Adult, Microbiology (medical), Receptors, CXCR4, Chemokine, Receptors, CCR5, Settore MED/17 - Malattie Infettive, Virus Attachment, HIV Infections, Biology, Peripheral blood mononuclear cell, Virus, Plasma, Cerebrospinal fluid, Virology, HIV tropism, Humans, Receptor, Tropism, Cerebrospinal Fluid, Middle Aged, Viral Tropism, Immunology, HIV-1, Leukocytes, Mononuclear, Tissue tropism, biology.protein
Abstract

A survey of HIV coreceptor usage in cerebrospinal fluid (CSF) samples, peripheral blood mononuclear cells (PBMCs), and plasma samples from naïve seropositive patients was conducted. One hundred patients were enrolled in this study. Of the 100 patients, 36 had a primary or recent infection (P-RI), 31 had an early chronic infection (>350 CD4 cells) (ECI), and 33 had a late chronic infection (LCI). All 3 compartments were sampled in a subset of 33 participants, while the remaining 67 patients provided plasma samples and PBMCs only. Seventy-seven patients harbored the R5 virus in plasma samples and had a significantly higher median and percentage of CD4 + T cells than patients with X4 virus (437 and 281 cells/μl, respectively; P = 0.0086; 20.6% and 18.6%, respectively). The X4 strain was detected more frequently in patients with LCI than in patients with P-RI or ECI (39.3%, 19.4%, and 9.6%, respectively; P = 0.0063). PBMC and plasma tropism was concordant in 90 patients, and 73 had the R5 strain. Among patients with discordant results, 4 had the R5 virus in their plasma and the X4 virus in PBMCs; 6 showed the opposite profile. Plasma, PBMC, and CSF tropism determinations were concordant in 26/33 patients (21 patients had R5, and 5 had X4). The tropism was discordant in 5/33 patients, with the X4 virus in plasma and R5 in CSF; the HIV tropism in PBMCs was X4 in 3 patients. The remaining 2/33 patients had the R5 virus in plasma and PBMCs and the X4 virus in CSF; one of these patients had a P-RI. The discordant tropism in CSF and blood may have implications for chemokine (C-C motif) receptor 5 (CCR5) antagonist use in patients with limited response to antiretroviral therapy (ART) or in responding patients evaluated for simplification of treatment.

Published
2011

49. KSHV DNA viremia correlates with low CD4+ cell count in Italian males at the time of diagnosis of HIV infection

Author

Giorgio Palù, Rodolfo Fuser, Renzo Scaggiante, Saverio Giuseppe Parisi, Vinicio Manfrin, Emanuele Nicastri, Sandro Panese, Maria Angela Biasolo, Massimo Andreoni, Marina Malena, Mario Cruciani, Loredana Sarmati, Samantha Andreis, Caterina Boldrin, Roberto Ferretto, and Luca Dori

Subjects
Male, Settore MED/17 - Malattie Infettive, viruses, Viremia, HIV Infections, medicine.disease_cause, Peripheral blood mononuclear cell, Herpesviridae, Virus, Virology, Immunopathology, medicine, Gammaherpesvirinae, Humans, biology, AIDS-Related Opportunistic Infections, virus diseases, Herpesviridae Infections, biochemical phenomena, metabolism, and nutrition, Viral Load, biology.organism_classification, medicine.disease, CD4 Lymphocyte Count, Infectious Diseases, Italy, Lentivirus, Immunology, DNA, Viral, Herpesvirus 8, Human, HIV-1, Viral disease
Abstract

To evaluate the relevance and the virological and immunological markers of Kaposi sarcoma herpesvirus 8 (KSHV) viremia in Italian male patients at the time of diagnosis of infection with HIV-1, 481 men infected with HIV were recruited consecutively. The presence of KSHV DNA was evaluated in peripheral blood mononuclear cells (PBMCs) and in plasma and correlated with demographic and viro-immunological parameters. Seventy-four patients had KSHV DNA detected in PBMCs. By univariate analysis, the presence of KSHV DNA was associated significantly with unprotected homosexual relationships (P=0.003) and it was significantly higher in patients with CD4+ cell

Published
2011

50. Strong and persistent correlation between baseline and follow-up HIV-DNA levels and residual viremia in a population of naïve patients with more than 4 years of effective antiretroviral therapy

Author

Massimo Andreoni, Carlo Mengoli, Giorgio Palù, Mario Cruciani, Loredana Sarmati, Vinicio Manfrin, Monica Basso, Samantha Andreis, Renzo Scaggiante, Saverio Giuseppe Parisi, and R. Ferretto

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, Longitudinal study, Genotype, Population, HIV Infections, Viremia, Gastroenterology, Persistence (computer science), Therapy naive, Correlation, Antiretroviral Therapy, Highly Active, Internal medicine, medicine, Humans, Longitudinal Studies, education, education.field_of_study, business.industry, General Medicine, Middle Aged, Viral Load, medicine.disease, Antiretroviral therapy, Settore MED/17, CD4 Lymphocyte Count, HIV-RNA, residual viremia, Treatment Outcome, Infectious Diseases, naïve patients, DNA, Viral, Immunology, primary infection, HIV-1, Leukocytes, Mononuclear, Female, Cellular HIV-DNA, business, Viral load, Follow-Up Studies
Abstract

In a longitudinal study on 181 naïve patients who responded to therapy (mean follow-up 4 years), high baseline human immunodeficiency virus (HIV)-RNA values correlated with high levels of cellular HIV-DNA at all time points (p

Published
2015
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