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Article ; Online: First case of persistent Stenotrophomonas maltophilia bacteraemia due to septic thrombosis successfully treated with a cefiderocol-containing regimen.

Medioli, Filippo / Casali, Elena / Viscido, Agnese / Pistolesi, Valentina / Venditti, Mario / Oliva, Alessandra

Journal of global antimicrobial resistance

2023 Volume 34, Page(s) 5–8

Abstract: Introduction: There is scarce evidence in literature of what should be the best antimicrobial treatment for bloodstream infections (BSIs) sustained by Stenotrophomonas maltophilia, a peculiar pathogen that intrinsically withstands to most of the ... ...

Abstract	Introduction: There is scarce evidence in literature of what should be the best antimicrobial treatment for bloodstream infections (BSIs) sustained by Stenotrophomonas maltophilia, a peculiar pathogen that intrinsically withstands to most of the available antibiotics. Results and conclusion: Here, we describe a challenging case of a persistent S. maltophilia BSI due to septic thrombosis successfully treated with the addition of the novel siderophore cephalosporin cefiderocol to an only partially effective levofloxacin regimen. Additionally, an intra-lock therapy with trimethoprim/sulfamethoxazole was selected as a strategy to prevent recurrence of infection since complete source control was not possible. The serum bactericidal assay was also used to corroborate the in vivo efficacy of the adopted combination therapy.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Cephalosporins/therapeutic use ; Stenotrophomonas maltophilia ; Humans ; Cefiderocol
Chemical Substances	Anti-Bacterial Agents ; Cephalosporins
Language	English
Publishing date	2023-06-10
Publishing country	Netherlands
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2710046-7
ISSN	2213-7173 ; 2213-7173
ISSN (online)	2213-7173
ISSN	2213-7173
DOI	10.1016/j.jgar.2023.05.013
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Article ; Online: Risk factors for carbapenem-resistant

Cogliati Dezza, Francesco / Covino, Sara / Petrucci, Flavia / Sacco, Federica / Viscido, Agnese / Gavaruzzi, Francesca / Ceccarelli, Giancarlo / Raponi, Gianmarco / Borrazzo, Cristian / Alessandri, Francesco / Mastroianni, Claudio Maria / Venditti, Mario / Oliva, Alessandra

JAC-antimicrobial resistance

2023 Volume 5, Issue 4, Page(s) dlad096

Abstract: Background: Among MDR bacteria, carbapenem-resistant : Objectives: The study assessed the risk factors for CRAB bloodstream infection (BSI) in patients admitted to the ICU with CRAB colonization, and the related mortality risk factors.: Methods: ... ...

Abstract	Background: Among MDR bacteria, carbapenem-resistant Objectives: The study assessed the risk factors for CRAB bloodstream infection (BSI) in patients admitted to the ICU with CRAB colonization, and the related mortality risk factors. Methods: We conducted a single-centre, observational, prospective study; all consecutive patients with CRAB colonization admitted to the ICU of a tertiary hospital in Rome from January 2021 to September 2022 were included in the study. Univariate and multivariate analyses were performed to investigate BSI and mortality risk factors. Results: Overall, 129 patients were included in the study; 57 (44%) out of these developed BSI. In our study population, at the multivariable analysis the Charlson comorbidity index (CCI) ( Conclusions: In critically ill patients colonized by CRAB, higher CCI, multisite colonization and the need for mechanical ventilation were identified as risk factors for BSI onset. These predictors could be useful to identify patients at highest risk of BSI.
Language	English
Publishing date	2023-08-10
Publishing country	England
Document type	Journal Article
ISSN	2632-1823
ISSN (online)	2632-1823
DOI	10.1093/jacamr/dlad096
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Article ; Online: Comparison by Age of the Local Interferon Response to SARS-CoV-2 Suggests a Role for IFN-ε and -ω.

Pierangeli, Alessandra / Gentile, Massimo / Oliveto, Giuseppe / Frasca, Federica / Sorrentino, Leonardo / Matera, Luigi / Nenna, Raffaella / Viscido, Agnese / Fracella, Matteo / Petrarca, Laura / D'Ettorre, Gabriella / Ceccarelli, Giancarlo / Midulla, Fabio / Antonelli, Guido / Scagnolari, Carolina

Frontiers in immunology

2022 Volume 13, Page(s) 873232

Abstract: Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS- ... ...

Abstract	Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS-CoV-2 response upon infection. To further characterize age-related differences, we studied type I and III interferon (IFN) response in SARS-CoV-2 infected and non-infected individuals of different ages. Specifically, levels of expression of type I (IFN-α, -β, -ε and -ω), type III (IFN-λ1, -λ2 and -λ3) IFNs and of the IFN-stimulated genes, ISG15 and ISG56 were quantified in nasopharyngeal cells from diagnostic swabs. Basal transcription of type I/III IFN genes was highest among children and decreased with age. Among SARS-CoV-2-infected individuals, only IFN-ε and -ω levels were significantly higher in children and young adults whereas ISGs were overexpressed in infected adults. The occurrence of symptoms in children and the need for hospitalization in adults were associated to higher transcription of several IFN genes. Starting from a pre-activated transcription level, the expression of type I and III IFNs was not highly up-regulated in children upon SARS-CoV-2 infection; young adults activated IFNs' transcription at intermediate levels whereas older adults were characterized by higher ISGs and lower IFN-ε and -ω relative expression levels. Overall, our findings contribute to recognize components of a protective IFN response as a function of age, in the context of SARS-CoV-2 infection.
MeSH term(s)	Aged ; Antiviral Agents ; COVID-19 ; Cell Line ; Child ; Humans ; Interferon Type I ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; Interferon Type I
Language	English
Publishing date	2022-07-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.873232
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Article ; Online: Analysis of serum microRNAs and rs2910164 GC single-nucleotide polymorphism of miRNA-146a in COVID-19 patients.

Pinacchio, Claudia / Scordio, Mirko / Santinelli, Letizia / Frasca, Federica / Sorrentino, Leonardo / Bitossi, Camilla / Oliveto, Giuseppe / Viscido, Agnese / Ceci, Flavio Maria / Celani, Luigi / Ceccarelli, Giancarlo / Antonelli, Guido / Mastroianni, Claudio Maria / d'Ettorre, Gabriella / Scagnolari, Carolina

Journal of immunoassay & immunochemistry

2022 Volume 43, Issue 4, Page(s) 347–364

Abstract: Alteration of micro-RNAs (miRNAs) expression, including miRNA-122a, -146a and -205 family members, can have profound effects on inflammatory and IFN pathways (miRNA-146a), known as hallmarks of COVID-19. SARS-CoV-2-infected patients were recruited at ... ...

Abstract	Alteration of micro-RNAs (miRNAs) expression, including miRNA-122a, -146a and -205 family members, can have profound effects on inflammatory and IFN pathways (miRNA-146a), known as hallmarks of COVID-19. SARS-CoV-2-infected patients were recruited at Policlinico Umberto I Hospital of Sapienza University of Rome (Italy). MiRNA-122a, -146a, -205 and IFI27 (Interferon Alpha Inducible Protein 27) levels were screened in SARS-CoV-2 patients (n = 14) and healthy controls (n = 10) by real-time RT-PCR assays. Then, miRNA-146a rs2910164 GC single-nucleotide polymorphism (SNP) was genotyped in a larger group of COVID-19 patients (n = 129), and its relationship with severe disease [Intensive Care Unit (ICU) support or survival/death] was assessed. SARS-CoV-2-positive patients had increased PCR, D-Dimer and Fibrinogen levels compared to healthy controls (p < .05 for all measurements). MiRNA-122a and -146a serum levels were upregulated in COVID-19 patients (miRNA-122a: p = .002; miRNA-146a: p < .001). Decreased IFI27 levels were observed in COVID-19 patients with higher miRNA-146a levels (p = .047). Moreover, miRNA-146a rs2910164 C/G genotypes distributions were similar in COVID-19 patients and in validated European healthy subjects (n = 37,214). MiRNA-146a SNP was not associated with severe COVID-19 outcome (ICU or death). MiRNA-122a and -146a levels were elevated in SARS-CoV-2 infected patients, with miRNA-146a upregulation possibly contributing to IFN pathways dysregulation (e.g., reduced IFI27 levels) observed in severe COVID-19, although there is no evidence for the involvement of rs2910164 SNP.
MeSH term(s)	Humans ; Case-Control Studies ; Circulating MicroRNA ; COVID-19/genetics ; Genetic Predisposition to Disease ; Genotype ; MicroRNAs/genetics ; Polymorphism, Single Nucleotide ; SARS-CoV-2
Chemical Substances	Circulating MicroRNA ; MicroRNAs ; MIRN146 microRNA, human
Language	English
Publishing date	2022-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2050610-7
ISSN	1532-4230 ; 1532-1819
ISSN (online)	1532-4230
ISSN	1532-1819
DOI	10.1080/15321819.2022.2035394
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Article ; Online: First COVID-19 lockdown resulted in most respiratory viruses disappearing among hospitalised children, with the exception of rhinoviruses.

Nenna, Raffaella / Matera, Luigi / Pierangeli, Alessandra / Oliveto, Giuseppe / Viscido, Agnese / Petrarca, Laura / La Regina, Domenico Paolo / Mancino, Enrica / Di Mattia, Greta / Villani, Alberto / Midulla, Fabio

Acta paediatrica (Oslo, Norway : 1992)

2022 Volume 111, Issue 7, Page(s) 1399–1403

Abstract: Aim: Emergency room admissions have decreased globally during the COVID-19 pandemic, particularly for respiratory diseases. We evaluated hospital admissions for respiratory diseases in the first year of the Italian pandemic and compared them with the ... ...

Abstract	Aim: Emergency room admissions have decreased globally during the COVID-19 pandemic, particularly for respiratory diseases. We evaluated hospital admissions for respiratory diseases in the first year of the Italian pandemic and compared them with the corresponding period in 2016-2017. Methods: The study was carried out at the Sapienza University in Rome, Italy, and covered 9 March to 28 February 2020-2021 and 2016-2017. We tested 85 hospitalised children who were negative for the virus that causes COVID-19 in 2020-2021 and compared them with 476 hospitalised children from 2016-2017, as we had also tested nasal washing samples for 14 respiratory viruses during that period. Results: Hospitalisations for acute respiratory tract infections were 82.2% lower in 2020-2021 than 2016-2017. The respiratory syncytial virus (RSV) and several other viruses were detected less frequently during the pandemic. An extraordinary finding was that rhinoviruses remained seasonal. In 2020-2021, we detected a virus in 54.1% of the hospitalised children: rhinoviruses in 41, RSV in 4 and other viruses in 1. This was significantly lower than the 71.6% in 2016-2017: RSV in 130, rhinoviruses in 128 and other viruses in 83. Conclusion: Pandemic measures dramatically reduced childhood respiratory infections, particularly RSV, but were less effective at reducing rhinoviruses.
MeSH term(s)	COVID-19/epidemiology ; COVID-19/prevention & control ; Child ; Child, Hospitalized ; Communicable Disease Control ; Humans ; Infant ; Pandemics ; Respiratory Syncytial Virus Infections/epidemiology ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Virus, Human ; Respiratory Tract Infections/epidemiology ; Respiratory Tract Infections/prevention & control ; Rhinovirus ; Viruses
Language	English
Publishing date	2022-03-16
Publishing country	Norway
Document type	Journal Article
ZDB-ID	203487-6
ISSN	1651-2227 ; 0365-1436 ; 0803-5253
ISSN (online)	1651-2227
ISSN	0365-1436 ; 0803-5253
DOI	10.1111/apa.16326
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Article: SARS-CoV-2 Entry Genes Expression in Relation with Interferon Response in Cystic Fibrosis Patients

Bitossi, Camilla / Frasca, Federica / Viscido, Agnese / Oliveto, Giuseppe / Scordio, Mirko / Belloni, Laura / Cimino, Giuseppe / Pietropaolo, Valeria / Gentile, Massimo / d’Ettorre, Gabriella / Midulla, Fabio / Trancassini, Maria / Antonelli, Guido / Pierangeli, Alessandra / Scagnolari, Carolina

Microorganisms. 2021 Jan. 03, v. 9, no. 1

2021

Abstract: The expression rate of SARS-CoV-2 entry genes, angiotensin-converting enzyme 2 (ACE2), the main viral receptor and the proteases, furin and transmembrane serine protease 2 (TMPRSS2) in cystic fibrosis (CF) individuals is poorly known. Hence, we examined ... ...

Abstract	The expression rate of SARS-CoV-2 entry genes, angiotensin-converting enzyme 2 (ACE2), the main viral receptor and the proteases, furin and transmembrane serine protease 2 (TMPRSS2) in cystic fibrosis (CF) individuals is poorly known. Hence, we examined their levels in upper respiratory samples of CF patients (n = 46) and healthy controls (n = 45). Moreover, we sought to understand the interplay of type I interferon (IFN-I) with ACE2, furin and TMPRSS2 by evaluating their gene expression with respect to ISG15, a well-known marker of IFN activation, in upper respiratory samples and after ex vivo IFNβ exposure. Lower ACE2 levels and trends toward the reduction of furin and TMPRSS2 were found in CF patients compared with the healthy controls; decreased ACE2 amounts were also detected in CF individuals with pancreatic insufficiency and in those receiving inhaled antibiotics. Moreover, there was a strong positive correlation between ISG15 and ACE2 levels. However, after ex vivo IFNβ stimulation of nasopharyngeal cells, the truncated isoform (dACE2), recently demonstrated as the IFN stimulated one with respect to the full-length isoform (flACE2), slightly augmented in cells from CF patients whereas in those from healthy donors, dACE2 levels showed variable levels of upregulation. An altered expression of SARS-COV-2 entry genes and a poor responsiveness of dACE2 to IFN-I stimulation might be crucial in the diffusion of SARS-CoV-2 infection in CF.
Keywords	antibiotics ; cells ; correlation ; cystic fibrosis ; diffusion ; gene expression ; genes ; infection ; interferons ; microorganisms ; patients ; peptidyl-dipeptidase A ; sampling ; serine proteinases
Language	English
Dates of publication	2021-0103
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9010093
Database	NAL-Catalogue (AGRICOLA)

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Article: KI and WU Polyomavirus in Respiratory Samples of SARS-CoV-2 Infected Patients

Prezioso, Carla / Moens, Ugo / Oliveto, Giuseppe / Brazzini, Gabriele / Piacentini, Francesca / Frasca, Federica / Viscido, Agnese / Scordio, Mirko / Guerrizio, Giuliana / Rodio, Donatella Maria / Pierangeli, Alessandra / d’Ettorre, Gabriella / Turriziani, Ombretta / Antonelli, Guido / Scagnolari, Carolina / Pietropaolo, Valeria

Microorganisms. 2021 June 09, v. 9, no. 6

2021

Abstract: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a global pandemic. Our goal was to determine whether co-infections with respiratory polyomaviruses, such as Karolinska Institutet polyomavirus (KIPyV) and Washington ... ...

Abstract	Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a global pandemic. Our goal was to determine whether co-infections with respiratory polyomaviruses, such as Karolinska Institutet polyomavirus (KIPyV) and Washington University polyomavirus (WUPyV) occur in SARS-CoV-2 infected patients. Oropharyngeal swabs from 150 individuals, 112 symptomatic COVID-19 patients and 38 healthcare workers not infected by SARS-CoV-2, were collected from March 2020 through May 2020 and tested for KIPyV and WUPyV DNA presence. Of the 112 SARS-CoV-2 positive patients, 27 (24.1%) were co-infected with KIPyV, 5 (4.5%) were positive for WUPyV, and 3 (2.7%) were infected simultaneously by KIPyV and WUPyV. Neither KIPyV nor WUPyV DNA was detected in samples of healthcare workers. Significant correlations were found in patients co-infected with SARS-CoV-2 and KIPyV (p < 0.05) and between SARS-CoV-2 cycle threshold values and KIPyV, WUPyV and KIPyV and WUPyV concurrently detected (p < 0.05). These results suggest that KIPyV and WUPyV may behave as opportunistic respiratory pathogens. Additional investigations are needed to understand the epidemiology and the prevalence of respiratory polyomavirus in COVID-19 patients and whether KIPyV and WUPyV could potentially drive viral interference or influence disease outcomes by upregulating SARS-CoV-2 replicative potential.
Keywords	COVID-19 infection ; DNA ; Human polyomavirus 3 ; Severe acute respiratory syndrome coronavirus 2 ; WU polyomavirus ; health services ; mixed infection ; pandemic
Language	English
Dates of publication	2021-0609
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9061259
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Article: Common Microbial Genital Infections and Their Impact on the Innate Immune Response to HPV in Cervical Cells.

Fracella, Matteo / Oliveto, Giuseppe / Sorrentino, Leonardo / Roberto, Piergiorgio / Cinti, Lilia / Viscido, Agnese / Di Lella, Federica Maria / Giuffrè, Federica / Gentile, Massimo / Pietropaolo, Valeria / Prezioso, Carla / Palma, Ettore / Recine, Nadia / Palaia, Innocenza / Scagnolari, Carolina / Antonelli, Guido / Pierangeli, Alessandra

Pathogens (Basel, Switzerland)

2022 Volume 11, Issue 11

Abstract: The persistence of high-risk (HR) human papillomavirus (HPV) genotypes is a prerequisite of cervical cancer. It is not clear whether and how bacterial vaginosis (BV) and sexually transmitted infections (STIs) cause higher rates of persistent HPV ... ...

Abstract	The persistence of high-risk (HR) human papillomavirus (HPV) genotypes is a prerequisite of cervical cancer. It is not clear whether and how bacterial vaginosis (BV) and sexually transmitted infections (STIs) cause higher rates of persistent HPV infection. This study aimed to characterize mucosal innate immunity to HPV, comparing different conditions. Specifically, expression levels of genes coding for Toll-like receptors (TLR)7 and 9, several type III Interferon-related genes (IFNL1, 2, 3, their specific receptor subunit IFNLR1, and the IFN-stimulated gene ISG15). Chemokines CCL5 and CCL20 were measured in cervical cells positive, or not, for HPV, BV, and STIs. HPV DNA was detected in 51/120 (42.5%) enrolled women, two/third were HR-HPV genotypes. More than 50% of samples were BV- and/or STI-positive. HPV-positive women had BV, but not other STIs, more frequently than the HPV-negative. TLR9 and IFNL1 mRNAs were expressed in the LR, but much less in the HR HPV infection. Enhanced levels of TLR9, TLR7, IFNL2, and IFNLR1 were observed in HPV-positive women with BV and STI. TLR9-increased expression was associated with HPV persistence in previous studies; hence, bacterial coinfections may enhance this risk. Prospective measurements of type III IFNs and IFNLR1 are warranted to evaluate whether this response may act as a double-edged sword in infected epithelia.
Language	English
Publishing date	2022-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11111361
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Article: SARS-CoV-2 Entry Genes Expression in Relation with Interferon Response in Cystic Fibrosis Patients.

Bitossi, Camilla / Frasca, Federica / Viscido, Agnese / Oliveto, Giuseppe / Scordio, Mirko / Belloni, Laura / Cimino, Giuseppe / Pietropaolo, Valeria / Gentile, Massimo / d'Ettorre, Gabriella / Midulla, Fabio / Trancassini, Maria / Antonelli, Guido / Pierangeli, Alessandra / Scagnolari, Carolina

Microorganisms

2021 Volume 9, Issue 1

Abstract	The expression rate of SARS-CoV-2 entry genes, angiotensin-converting enzyme 2 (ACE2), the main viral receptor and the proteases, furin and transmembrane serine protease 2 (TMPRSS2) in cystic fibrosis (CF) individuals is poorly known. Hence, we examined their levels in upper respiratory samples of CF patients (
Language	English
Publishing date	2021-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9010093
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Article ; Online: ACE2 expression is related to the interferon response in airway epithelial cells but is that functional for SARS-CoV-2 entry?

Scagnolari, Carolina / Bitossi, Camilla / Viscido, Agnese / Frasca, Federica / Oliveto, Giuseppe / Scordio, Mirko / Petrarca, Laura / Mancino, Enrica / Nenna, Raffaella / Riva, Elisabetta / De Vito, Corrado / Midulla, Fabio / Antonelli, Guido / Pierangeli, Alessandra

Cytokine

2021 Volume 140, Page(s) 155430

Abstract: In vitro interferon (IFN)α treatment of primary human upper airway basal cells has been shown to drive ACE2 expression, the receptor of SARS-CoV-2. The protease furin is also involved in mediating SARS-CoV-2 and other viral infections, although its ... ...

Abstract	In vitro interferon (IFN)α treatment of primary human upper airway basal cells has been shown to drive ACE2 expression, the receptor of SARS-CoV-2. The protease furin is also involved in mediating SARS-CoV-2 and other viral infections, although its association with early IFN response has not been evaluated yet. In order to assess the in vivo relationship between ACE2 and furin expression and the IFN response in nasopharyngeal cells, we first examined ACE2 and furin levels and their correlation with the well-known marker of IFNs' activation, ISG15, in children (n = 59) and adults (n = 48), during respiratory diseases not caused by SARS-CoV-2. A strong positive correlation was found between ACE2 expression, but not of furin, and ISG15 in all patients analyzed. In addition, type I and III IFN stimulation experiments were performed to examine the IFN-mediated activation of ACE2 isoforms (full-length and truncated) and furin in epithelial cell lines. Following all the IFNs treatments, only the truncated ACE2 levels, were upregulated significantly in the A549 and Calu3 cells, in particular by type I IFNs. If confirmed in vivo following IFNs' activation, the induction of the truncated ACE2 isoform only would not enhance the risk of SARS-CoV-2 infection in the respiratory tract.
MeSH term(s)	A549 Cells ; Adult ; Angiotensin-Converting Enzyme 2/genetics ; Antiviral Agents/metabolism ; Antiviral Agents/pharmacology ; COVID-19/prevention & control ; COVID-19/virology ; Cell Line, Tumor ; Child ; Cytokines/genetics ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Gene Expression/drug effects ; Humans ; Interferons/metabolism ; Interferons/pharmacology ; Lung/cytology ; Middle Aged ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Ubiquitins/genetics
Chemical Substances	Antiviral Agents ; Cytokines ; Ubiquitins ; ISG15 protein, human (60267-61-0) ; Interferons (9008-11-1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-01-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2021.155430
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