Valentino Costabile
@ospedalebambinogesu
Microbiology and Immunological Diagnostics
Ospedale Pediatrico Bambino Gesù
EDUCATION
Biotechnology - Bioinformatics
RESEARCH, TEACHING, or OTHER INTERESTS
Microbiology (medical), Immunology and Microbiology, Cancer Research, Software
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Angela Mastronuzzi, Rita Carsetti, Maria Antonietta De Ioris, Chiara Agrati, Giada Del Baldo, Cristina Russo, Maria Giuseppina Cefalo, Pietro Merli, Carlo Federico Perno, Vito Andrea dell'Anna,et al.
Elsevier BV
Sabrina Rossi, Sabina Barresi, Giovanna Stefania Colafati, Silvia Genovese, Chantal Tancredi, Valentino Costabile, Sara Patrizi, Isabella Giovannoni, Sofia Asioli, Pietro Luigi Poliani,et al.
Elsevier BV
Francesca Lombardi, Elena Bruzzesi, Yagai Romeo Bouba, Domenico Di Carlo, Valentino Costabile, Martina Ranzenigo, Franco Maggiolo, Antonella Castagna, Anna Paola Callegaro, Alessia Zoncada,et al.
Mary Ann Liebert Inc
Despite effective antiretroviral therapies (ART), a subset of people living with HIV (PLWH) still experience low-level viremia (LLV, i.e. 50-1000 copies/mL). The present study compared PLWH experiencing LLV to those maintaining viral suppression (VS) and explored the potential impact of pre-existing drug resistance and other factors on LLV. We conducted a retrospective, 1:1 matched case-control study within a cohort of drug-experienced virologically suppressed subjects from the Italian ARCA database, followed in the period 2009-2019. Cases were individuals experiencing LLV, while controls were those who maintained VS. Matching was for calendar year of first ART regimen. Pre-existing drug resistance was calculated as cumulative genotypic susceptibility score (GSS) according to regimen administered at the observational period start. To explore the effect of cumulative GSS, treated as a binary variable (≥2 and <2) and other factors on LLV, we performed a logistic regression analysis. Within a main population of 3,455 PLWH, 337 cases were selected. Cases were comparable to the controls for both gender and age. However, cases showed that they'd experienced a longer time since HIV diagnosis, a higher number of drugs previously administered, lower baseline CD4+ T cells count and a higher zenith viral load (VL). By multivariate analysis, we found that higher zenith VL (aOR [95% C.I.] 1.30 [1.14-1.48]), a cumulative usage of both PI (aOR [95% CI]: 2.03 [1.19-3.48]) and InSTI (aOR [95% CI]: 2.23 [1.47-3.38]) and a cumulative GSS <2 (aOR [95% CI] 0.67 [0.46-0.98]), were associated with a higher risk in developing LLV. In current high efficacy ART era, in drug-experienced PLWH the predictors of increased risk of LLV were the presence of pre-existing drug resistance, higher zenith viral load, and previous PI, and InSTI exposure.
Rossana Scutari, Valeria Fox, Maria Antonietta De Ioris, Vanessa Fini, Annarita Granaglia, Valentino Costabile, Luna Colagrossi, Cristina Russo, Angela Mastronuzzi, Franco Locatelli,et al.
Springer Science and Business Media LLC
Abstract Background Since its emergence in November 2021, SARS-CoV-2 Omicron clade has quickly become dominant, due to its increased transmissibility and immune evasion. Different sublineages are currently circulating, which differ in mutations and deletions in regions of the SARS-CoV-2 genome implicated in the immune response. In May 2022, BA.1 and BA.2 were the most prevalent sublineages in Europe, both characterized by ability of evading natural acquired and vaccine-induced immunity and of escaping monoclonal antibodies neutralization. Case presentation A 5-years old male affected by B-cell acute lymphoblastic leukemia in reinduction was tested positive for SARS-CoV-2 by RT-PCR at the Bambino Gesù Children Hospital in Rome in December 2021. He experienced a mild COVID-19 manifestation, and a peak of nasopharyngeal viral load corresponding to 15.5 Ct. Whole genome sequencing identified the clade 21 K (Omicron), sublineage BA.1.1. The patient was monitored over time and tested negative for SARS-CoV-2 after 30 days. Anti-S antibodies were detected positive with modest titre (3.86 BAU/mL), while anti-N antibodies were negative. 74 days after the onset of the first infection and 23 days after the last negative test, the patient was readmitted to hospital with fever, and tested positive for SARS-CoV-2 by RT-PCR (peak of viral load corresponding to 23.3 Ct). Again, he experienced a mild COVID-19. Whole genome sequencing revealed an infection with the Omicron lineage BA.2 (21L clade). Sotrovimab administration was started at the fifth day of positivity, and RT-PCR negativity occurred 10 days later. Surveillance SARS-CoV-2 RT-PCR were persistently negative, and in May 2022, anti-N antibodies were found positive and anti-S antibodies reached titres > 5000 BAU/mL. Conclusions By this clinical case, we showed that SARS-CoV-2 reinfection within the Omicron clade can occur and can be correlated to inadequate immune responses to primary infection. We also showed that the infection’s length was shorter in the second respect to first episode, suggesting that pre-existing T cell-mediated immunity, though not preventing re-infection, might have limited the SARS-CoV-2 replication capacity. Lastly, Sotrovimab treatment retained activity against BA.2, probably accelerating the viral clearance in the second infectious episode, after which seroconversion and increase of anti-S antibodies titres were observed.
Martina Rossitto, Gianluca Vrenna, Vanessa Tuccio Guarna Assanti, Nour Essa, Maria Luisa De Santis, Annarita Granaglia, Vanessa Fini, Valentino Costabile, Manuela Onori, Luca Cristiani,et al.
MDPI AG
Acinetobacter baumannii is one of the pathogens most involved in health care-associated infections in recent decades. Known for its ability to accumulate several antimicrobial resistance mechanisms, it possesses the oxacillinase blaoxa-23, a carbapenemase now endemic in Italy. Acinetobacter species are not frequently observed in patients with cystic fibrosis, and multidrug-resistant A. baumannii is a rare event in these patients. Non-mucoid A. baumannii carrying the blaoxa-23 gene has been sporadically detected. Here, we describe the methods used to detect blaoxa-23 in the first established case of pulmonary infection via a mucoid strain of A. baumannii producing carbapenemase in a 24-year-old cystic fibrosis patient admitted to Bambino Gesù Children’s Hospital in Rome, Italy. This strain, which exhibited an extensively drug-resistant antibiotype, also showed a great ability to further increase its resistance in a short time.
Costanza Tripiciano, Lorenza Romani, Stefania Mercadante, Laura Cursi, Martina Di Giuseppe, Francesca Ippolita Calo Carducci, Tiziana Fragasso, Luca Di Chiara, Cristiana Garisto, Annamaria Sisto,et al.
MDPI AG
Background: The spread of carbapenem-resistant organisms (CROs) is an increasingly serious threat globally, especially in vulnerable populations, such as intensive care unit (ICU) patients. Currently, the antibiotic options for CROs are very limited, particularly in pediatric settings. We describe a cohort of pediatric patients affected by CRO infections, highlighting the important changes in carbapenemase production in recent years and comparing the treatment with novel cephalosporins (N-CEFs) to Colistin-based regimens (COLI). Methods: All patients admitted to the cardiac ICU of the Bambino Gesù Children’s Hospital in Rome during the 2016–2022 period with an invasive infection caused by a CRO were enrolled. Results: The data were collected from 42 patients. The most frequently detected pathogens were Pseudomonas aeruginosa (64%), Klebsiella pneumoniae (14%) and Enterobacter spp. (14%). Thirty-three percent of the isolated microorganisms were carbapenemase producers, with a majority of VIM (71%), followed by KPC (22%) and OXA-48 (7%). A total of 67% of patients in the N-CEF group and 29% of patients in the comparative group achieved clinical remission (p = 0.04). Conclusion: The increase over the years of MBL-producing pathogens in our hospital is challenging in terms of therapeutic options. According to the present study, N-CEFs are a safe and effective option in pediatric patients affected by CRO infections.
Claudia Alteri, Valeria Fox, Rossana Scutari, Giulia Jole Burastero, Sara Volpi, Matteo Faltoni, Vanessa Fini, Annarita Granaglia, Sara Esperti, Altea Gallerani,et al.
Springer Science and Business Media LLC
AbstractLittle is known about SARS-CoV-2 evolution under Molnupiravir and Paxlovid, the only antivirals approved for COVID-19 treatment. By investigating SARS-CoV-2 variability in 8 Molnupiravir-treated, 7 Paxlovid-treated and 5 drug-naïve individuals at 4 time-points (Days 0-2-5-7), a higher genetic distance is found under Molnupiravir pressure compared to Paxlovid and no-drug pressure (nucleotide-substitutions/site mean±Standard error: 18.7 × 10−4 ± 2.1 × 10−4 vs. 3.3 × 10−4 ± 0.8 × 10−4 vs. 3.1 × 10−4 ± 0.8 × 10−4, P = 0.0003), peaking between Day 2 and 5. Molnupiravir drives the emergence of more G-A and C-T transitions than other mutations (P = 0.031). SARS-CoV-2 selective evolution under Molnupiravir pressure does not differ from that under Paxlovid or no-drug pressure, except for orf8 (dN > dS, P = 0.001); few amino acid mutations are enriched at specific sites. No RNA-dependent RNA polymerase (RdRp) or main proteases (Mpro) mutations conferring resistance to Molnupiravir or Paxlovid are found. This proof-of-concept study defines the SARS-CoV-2 within-host evolution during antiviral treatment, confirming higher in vivo variability induced by Molnupiravir compared to Paxlovid and drug-naive, albeit not resulting in apparent mutation selection.
Claudia Alteri, Rossana Scutari, Valentino Costabile, Luna Colagrossi, Katia Yu La Rosa, Emanuele Agolini, Valentina Lanari, Sara Chiurchiù, Lorenza Romani, Anna Hermine Markowich,et al.
Springer Science and Business Media LLC
Claudia Alteri, Rossana Scutari, Valentino Costabile, Luna Colagrossi, Katia Yu La Rosa, Emanuele Agolini, Valentina Lanari, Sara Chiurchiù, Lorenza Romani, Anna Hermine Markowich,et al.
Springer Science and Business Media LLC
AbstractSince the start of SARS-CoV-2 pandemic, children aged ≤ 12 years have always been defined as underrepresented in terms of SARS-CoV-2 infections’ frequency and severity. By correlating SARS-CoV-2 transmission dynamics with clinical and virological features in 612 SARS-CoV-2 positive patients aged ≤ 12 years, we demonstrated a sizeable circulation of different SARS-CoV-2 lineages over the four pandemic waves in paediatric population, sustained by local transmission chains. Age < 5 years, highest viral load, gamma and delta clades positively influence this local transmission. No correlations between COVID-19 manifestations and lineages or transmission chains are seen, except for a negative correlation between B.1.1.7 and hospitalization.
Luna Colagrossi, Valentino Costabile, Rossana Scutari, Valeria Cento, Luana Coltella, Antonino Reale, Martina Scilipoti, Alberto Villani, Claudia Alteri, Carlo Federico Perno,et al.
Frontiers Media SA
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has increased the need to identify additional rapid diagnostic tests for an accurate and early diagnosis of infection. Here, we evaluated the diagnostic performance of the cartridge-based reverse transcription polymerase chain reaction (RT-PCR) test STANDARD M10 SARS-CoV-2 (SD Biosensor Inc., Suwon, South Korea), targeting the ORF1ab and E gene of SARS-CoV-2, and which can process up to eight samples in parallel in 60 min. From January 2022 to March 2022, STANDARD™ M10 assay performance was compared with Xpert® Xpress SARS-CoV-2 (Cepheid, Sunnyvale CA) on 616 nasopharyngeal swabs from consecutive pediatric (N = 533) and adult (N = 83) patients presenting at the “Istituto di Ricovero e Cura a Carattere Scientifico” (IRCCS) Ospedale Pediatrico Bambino Gesù, Roma. The overall performance of STANDARD M10 SARS-CoV-2 was remarkably and consistently comparable to the Xpert® Xpress SARS-CoV-2 with an overall agreement of 98% (604/616 concordant results), and negligible differences in time-to-result (60 min vs. 50 min, respectively). When the Xpert® Xpress SARS-CoV-2 results were considered as the reference, STANDARD™ M10 SARS-CoV-2 had 96.5% sensitivity and 98.4% specificity. STANDARD M10 SARS-CoV-2 can thus be safely included in diagnostic pathways because it rapidly and accurately identifies SARS-CoV-2 present in nasopharyngeal swabs.
Luna Colagrossi, Valentino Costabile, Rossana Scutari, Marilena Agosta, Manuela Onori, Livia Mancinelli, Barbara Lucignano, Andrea Onetti Muda, Giada Del Baldo, Angela Mastronuzzi,et al.
Informa UK Limited
ABSTRACT Owing to an increasing number of infections in adults, Lactococcus (L.) garvieae has gained recognition as an emerging human pathogen, causing bacteraemia and septicaemia. In September 2020, four paediatric onco-hematologic patients received a platelet concentrate from the same adult donor at Bambino Gesù Children’s Hospital IRCCS, Rome. Three of four patients experienced L. garvieae sepsis one day after transfusion. The L. garvieae pediatric isolates and the donor’s platelet concentrates were retrospectively collected for whole-genome sequencing and shot-gun metagenomics, respectively (Illumina HiSeq). By de novo assembly of the L. garvieae genomes, we found that all three pediatric isolates shared a 99.9% identity and were characterized by 440 common SNPs. Plasmid pUC11C (conferring virulence properties) and the temperate prophage Plg-Tb25 were detected in all three strains. Core SNP genome-based maximum likelihood and Bayesian trees confirmed their phylogenetic common origin and revealed their relationship with L. garvieae strains affecting cows and humans (bootstrap values >100 and posterior probabilities = 1.00). Bacterial reads obtained by the donor’s platelet concentrate have been profiled with MetaPhlAn2 (v.2.7.5); among these, 29.9% belonged to Firmicutes, and 5.16% to Streptococcaceae (>97% identity with L. garvieae), confirming the presence of L. garvieae in the platelet concentrate transfusion. These data showed three episodes of sepsis for the first time due to a transfusion-associated transmission of L. garvieae in three pediatric hospitalized hematology patients. This highlights the importance to implement the screening of platelet components with new human-defined pathogens for ensuring the safety of blood supply, and more broadly, for the surveillance of emerging pathogens.
Claudia Alteri, Valeria Cento, Antonio Piralla, Valentino Costabile, Monica Tallarita, Luna Colagrossi, Silvia Renica, Federica Giardina, Federica Novazzi, Stefano Gaiarsa,et al.
Springer Science and Business Media LLC
AbstractFrom February to April 2020, Lombardy (Italy) reported the highest numbers of SARS-CoV-2 cases worldwide. By analyzing 346 whole SARS-CoV-2 genomes, we demonstrate the presence of seven viral lineages in Lombardy, frequently sustained by local transmission chains and at least two likely to have originated in Italy. Six single nucleotide polymorphisms (five of them non-synonymous) characterized the SARS-CoV-2 sequences, none of them affecting N-glycosylation sites. The seven lineages, and the presence of local transmission clusters within three of them, revealed that sustained community transmission was underway before the first COVID-19 case had been detected in Lombardy.
Rossana Scutari, Valentino Costabile, Laura Galli, Maria Concetta Bellocchi, Luca Carioti, Silvia Barbaliscia, Andrea Poli, Andrea Galli, Carlo Federico Perno, Maria Mercedes Santoro,et al.
MDPI AG
Background: If analytical antiretroviral-treatment (ART) interruption (ATI) might significantly impact quantitative or qualitative peripheral-total HIV-DNA is still debated. Methods: Six chronically HIV-1 infected patients enrolled in APACHE-study were analysed for peripheral-total HIV-DNA and residual viremia, major-resistance-mutations (MRMs) and C2-V3-C3 evolution at pre-ATI (T1), during ATI (T2) and at achievement of virological success after ART-resumption (post-ATI, T3). These data were obtained at three comparable time-points in five chronically HIV-1 infected patients on suppressive ART for ≥1 year, enrolled in MODAt-study. Results: At T1, APACHE and MODAt individuals had similar peripheral-total HIV-DNA and residual viremia (p = 0.792 and 0.662, respectively), and no significant changes for these parameters were observed between T1 and T3 in both groups. At T1, 4/6 APACHE and 2/5 MODAt carried HIV-DNA MRMs. MRMs disappeared at T3 in 3/4 APACHE. All disappearing MRMs were characterized by T1 intra-patient prevalence <80%, and mainly occurred in APOBEC3-related sites. All MRMs persisted over-time in the 2 MODAt. C2-V3-C3 genetic-distance significantly changed from T1 to T3 in APACHE individuals (+0.36[0.11–0.41], p = 0.04), while no significant changes were found in MODAt. Accordingly, maximum likelihood trees (bootstrap > 70%) and genealogical sorting indices (GSI > 0.50 with p-value < 0.05) showed that T1 C2-V3-C3 DNA sequences were distinct from T2 and T3 viruses in 4/6 APACHE. Virus populations at all three time-points were highly interspersed in MODAt. Conclusions: This pilot study indicates that short ATI does not alter peripheral-total HIV-DNA burden and residual viremia, but in some cases could cause a genetic diversification of peripheral viral reservoir in term of both MRMs rearrangement and viral evolution.
Claudia Alteri, Valeria Cento, Marta Vecchi, Luna Colagrossi, Diana Fanti, Chiara Vismara, Massimo Puoti, Carlo Federico Perno, Claudia Alteri, Maria Antonello,et al.
Oxford University Press (OUP)
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Nasopharyngeal SARS-CoV-2 load at hospital admission as predictor of mortality
Claudia Alteri, Valeria Cento, Maria Antonello, Luna Colagrossi, Marco Merli, Nicola Ughi, Silvia Renica, Elisa Matarazzo, Federica Di Ruscio, Livia Tartaglione,et al.
Public Library of Science (PLoS)
Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57–84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P<0.001). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients.
Valeria Cento, Luna Colagrossi, Alice Nava, Anna Lamberti, Sabrina Senatore, Giovanna Travi, Roberto Rossotti, Marta Vecchi, Ornella Casati, Elisa Matarazzo,et al.
Elsevier BV
Neri Niccolai, Edoardo Morandi, Simone Gardini, Valentino Costabile, Roberta Spadaccini, Orlando Crescenzi, Delia Picone, Ottavia Spiga, and Andrea Bernini
Elsevier BV