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Article ; Online: SARS-CoV-2-specific mucosal immune response in vaccinated versus infected children.

Conti, Maria Giulia / Piano Mortari, Eva / Nenna, Raffaella / Pierangeli, Alessandra / Sorrentino, Leonardo / Frasca, Federica / Petrarca, Laura / Mancino, Enrica / Di Mattia, Greta / Matera, Luigi / Fracella, Matteo / Albano, Christian / Scagnolari, Carolina / Capponi, Martina / Cinicola, Bianca / Carsetti, Rita / Midulla, Fabio

Frontiers in cellular and infection microbiology

2024 Volume 14, Page(s) 1231697

Abstract: The anti-COVID-19 intramuscular vaccination induces a strong systemic but a weak mucosal immune response in adults. Little is known about the mucosal immune response in children infected or vaccinated against SARS-CoV-2. We found that 28% of children had ...

Abstract	The anti-COVID-19 intramuscular vaccination induces a strong systemic but a weak mucosal immune response in adults. Little is known about the mucosal immune response in children infected or vaccinated against SARS-CoV-2. We found that 28% of children had detectable salivary IgA against SARS-CoV-2 even before vaccination, suggesting that, in children, SARS-CoV-2 infection may be undiagnosed. After vaccination, only receptor-binding domain (RBD)-specific IgA1 significantly increased in the saliva. Conversely, infected children had significantly higher salivary RBD-IgA2 compared to IgA1, indicating that infection more than vaccination induces a specific mucosal immune response in children. Future efforts should focus on development of vaccine technologies that also activate mucosal immunity.
MeSH term(s)	Adult ; Child ; Humans ; Immunity, Mucosal ; SARS-CoV-2 ; COVID-19 ; Immunoglobulin A ; Mucous Membrane ; Vaccination ; Antibodies, Viral
Chemical Substances	Immunoglobulin A ; Antibodies, Viral
Language	English
Publishing date	2024-03-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2024.1231697
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Article ; Online: Age-related transcript changes in type I interferon signaling in children and adolescents with long COVID.

Fracella, Matteo / Mancino, Enrica / Nenna, Raffaella / Virgillito, Chiara / Frasca, Federica / D'Auria, Alessandra / Sorrentino, Leonardo / Petrarca, Laura / La Regina, Domenico / Matera, Luigi / Di Mattia, Greta / Caputo, Beniamino / Antonelli, Guido / Pierangeli, Alessandra / Viscidi, Raphael P / Midulla, Fabio / Scagnolari, Carolina

European journal of immunology

2024 Volume 54, Issue 5, Page(s) e2350682

Abstract: SARS-CoV-2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN-I) ... ...

Abstract	SARS-CoV-2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN-I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age-matched SARS-CoV-2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN-I (IFN-α/β/ε/ω), IFN-I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3-6 months after COVID-19. LC adolescents (12-17 years) had higher transcript levels of IFN-β, IFN-ε, and IFN-ω than HC, whereas LC children (6-11 years) had lower levels than HC. In adolescents, increased levels of IFN-α, IFN-β, and IFN-ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN-α/β mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age-related changes in the expression of transcripts involved in the IFN-I signaling pathway in children and adolescents with LC.
MeSH term(s)	Humans ; Child ; Adolescent ; Interferon Type I/metabolism ; Interferon Type I/immunology ; Interferon Type I/genetics ; Male ; COVID-19/immunology ; Female ; Signal Transduction/immunology ; SARS-CoV-2/immunology ; Immunity, Innate ; Age Factors ; Post-Acute COVID-19 Syndrome ; RNA, Messenger/genetics
Chemical Substances	Interferon Type I ; RNA, Messenger
Language	English
Publishing date	2024-03-24
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202350682
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Article: NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially Expressed in Respiratory-Syncytial-Virus- and Rhinovirus-Infected Hospitalized Children.

Sorrentino, Leonardo / Toscanelli, Walter / Fracella, Matteo / De Angelis, Marta / Frasca, Federica / Scagnolari, Carolina / Petrarca, Laura / Nenna, Raffaella / Midulla, Fabio / Palamara, Anna Teresa / Nencioni, Lucia / Pierangeli, Alessandra

Pathogens (Basel, Switzerland)

2023 Volume 12, Issue 4

Abstract: Respiratory diseases caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV) are frequent causes of the hospitalization of children; nonetheless, RSV is responsible for the most severe and life-threatening illnesses. Viral infection ... ...

Abstract	Respiratory diseases caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV) are frequent causes of the hospitalization of children; nonetheless, RSV is responsible for the most severe and life-threatening illnesses. Viral infection triggers an inflammatory response, activating interferon (IFN)-mediated responses, including IFN-stimulated genes (ISG) expression with antiviral and immunomodulatory activities. In parallel, the reactive oxygen species (ROS) production activates nuclear factor erythroid 2-related factor 2 (NRF2), whose antioxidant activity can reduce inflammation by interacting with the NF-kB pathway and the IFN response. To clarify how the interplay of IFN and NRF2 may impact on clinical severity, we enrolled children hospitalized for bronchiolitis and pneumonia, and measured gene expression of type-I and III IFNs, of several ISGs, of NRF2 and antioxidant-related genes, i.e., glucose-6-phosphate dehydrogenase (G6PD), heme oxygenase 1 (HO1), and NAD(P)H dehydrogenase [Quinone] 1 (NQO1) in RSV- (RSV-A N = 33 and RSV-B N = 30) and HRV (N = 22)-positive respiratory samples. NRF2 and HO1 expression is significantly elevated in children with HRV infection compared to RSV (
Language	English
Publishing date	2023-04-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens12040577
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Article: In Vitro Virucidal Effects of Ultraviolet Light Prototypes on RNA viruses.

Fracella, Matteo / Scordio, Mirko / Sorrentino, Leonardo / D'Auria, Alessandra / Ingenito, Raffaele / Gentile, Massimo / Pierangeli, Alessandra / Antonelli, Guido / Scagnolari, Carolina / Frasca, Federica

The new microbiologica

2023 Volume 46, Issue 2, Page(s) 161–169

Abstract: Ultraviolet-C (UVC) has been used to cause virus inactivation. The virucidal activity of three UV light lamps [UVC high frequencies (HF), UVC+B LED and UVC+A LED] was evaluated against the enveloped feline coronavirus (FCoVII), a surrogate model of SARS- ... ...

Abstract	Ultraviolet-C (UVC) has been used to cause virus inactivation. The virucidal activity of three UV light lamps [UVC high frequencies (HF), UVC+B LED and UVC+A LED] was evaluated against the enveloped feline coronavirus (FCoVII), a surrogate model of SARS-CoV-2, the enveloped vesicular stomatitis virus (VSV), and the naked encephalomyocarditis virus (EMCV). Virucidal assays were performed at different time points of UV-light exposure (i.e., 5, 30 minutes and 1, 6, and 8 hours), placing each virus 180 cm below the perpendicular irradiation of the lamp and 1 and 2 meters from the perpendicular axis. We found that the UVC HF lamp had virucidal effects (≥96.8% of virus inactivation) against FCoVII, VSV and EMCV after 5 minutes of irradiation at each distance analyzed. Moreover, the UVC+B LED lamp had the highest inhibitory effects on FCoVII and VSV infectivity (≥99% of virus inactivation) when these viruses were settled below the perpendicular axis of the lamp for 5 minutes. Conversely, the UVC+A LED lamp was the least effective, achieving ≥85.9% inactivation of enveloped RNA viruses after 8 hours of UV exposure. Overall, UV light lamps, and in particular UVC HF and UVC+B LED ones, had a rapid and strong virucidal activity against distinct RNA viruses, including coronaviruses.
MeSH term(s)	Humans ; Ultraviolet Rays ; SARS-CoV-2 ; COVID-19 ; Disinfection ; Viruses
Language	English
Publishing date	2023-05-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	756168-4
ISSN	1121-7138 ; 0391-5352
ISSN	1121-7138 ; 0391-5352
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Article: Distribution of Interferon Lambda 4 Single Nucleotide Polymorphism rs11322783 Genotypes in Patients with COVID-19

Sorrentino, Leonardo / Silvestri, Valentina / Oliveto, Giuseppe / Scordio, Mirko / Frasca, Federica / Fracella, Matteo / Bitossi, Camilla / D’Auria, Alessandra / Santinelli, Letizia / Gabriele, Lucia / Pierangeli, Alessandra / Mastroianni, Claudio Maria / d’Ettorre, Gabriella / Antonelli, Guido / Caruz, Antonio / Ottini, Laura / Scagnolari, Carolina

Microorganisms. 2022 Feb. 04, v. 10, no. 2

2022

Abstract: Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We ... ...

Abstract	Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We analyzed the genotype frequencies of IFNL4 single nucleotide polymorphism (SNP) rs11322783 in patients with COVID-19 (n = 128), in comparison with a validated data set of European healthy controls (n = 14152). The IFNL4 SNP was also analyzed according to the haematological and clinical parameters of patients with COVID-19. The distributions of IFNL4 genotypes among SARS-CoV-2 positive patients [TT/TT 41.4% (n = 53), TT/ΔG 47.7% (n = 61) and ΔG/ΔG 10.9% (n = 14)] and healthy controls were comparable. Different levels of white blood cells (p = 0.036) and neutrophils (p = 0.042) were found in the IFNL4 different genotypes in patients with COVID-19; the ΔG/ΔG genotype was more represented in the groups with low white blood cells and neutrophils. There were no differences in major inflammation parameters (C-reactive protein, D-dimer, Albumin, and Lactate-dehydrogenase (LDH)] and survival rate according to the IFNL4 genotypes. In conclusion, although patients with COVID-19 did not exhibit a different distribution of the IFNL4 SNP, the ΔG/ΔG genotype was associated with a lower count of immune cell populations. These findings need to be confirmed in larger groups of patients with COVID-19 and the role of IFNL4 SNP needs to be also investigated in other respiratory viral infections.
Keywords	C-reactive protein ; COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; albumins ; data collection ; genotype ; inflammation ; interferons ; lactate dehydrogenase ; neutrophils ; single nucleotide polymorphism ; survival rate
Language	English
Dates of publication	2022-0204
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms10020363
Database	NAL-Catalogue (AGRICOLA)

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Article: Alterations in the Expression of IFN Lambda, IFN Gamma and Toll-like Receptors in Severe COVID-19 Patients.

Sorrentino, Leonardo / Fracella, Matteo / Frasca, Federica / D'Auria, Alessandra / Santinelli, Letizia / Maddaloni, Luca / Bugani, Ginevra / Bitossi, Camilla / Gentile, Massimo / Ceccarelli, Giancarlo / Turriziani, Ombretta / Mastroianni, Claudio Maria / Antonelli, Guido / d'Ettorre, Gabriella / Pierangeli, Alessandra / Scagnolari, Carolina

Microorganisms

2023 Volume 11, Issue 3

Abstract: Contradictory results have been reported regarding interferon (IFN) lambda (λ1-3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1-3 and IFNγ mRNA expression was ... ...

Abstract	Contradictory results have been reported regarding interferon (IFN) lambda (λ1-3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1-3 and IFNγ mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) (
Language	English
Publishing date	2023-03-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11030689
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Article: Natural Flavonoid Derivatives Have Pan-Coronavirus Antiviral Activity.

Mori, Mattia / Quaglio, Deborah / Calcaterra, Andrea / Ghirga, Francesca / Sorrentino, Leonardo / Cammarone, Silvia / Fracella, Matteo / D'Auria, Alessandra / Frasca, Federica / Criscuolo, Elena / Clementi, Nicola / Mancini, Nicasio / Botta, Bruno / Antonelli, Guido / Pierangeli, Alessandra / Scagnolari, Carolina

Microorganisms

2023 Volume 11, Issue 2

Abstract: The SARS-CoV-2 protease (3CLpro) is one of the key targets for the development of efficacious drugs for COVID-19 treatment due to its essential role in the life cycle of the virus and exhibits high conservation among coronaviruses. Recent studies have ... ...

Abstract	The SARS-CoV-2 protease (3CLpro) is one of the key targets for the development of efficacious drugs for COVID-19 treatment due to its essential role in the life cycle of the virus and exhibits high conservation among coronaviruses. Recent studies have shown that flavonoids, which are small natural molecules, have antiviral activity against coronaviruses (CoVs), including SARS-CoV-2. In this study, we identified the docking sites and binding affinity of several natural compounds, similar to flavonoids, and investigated their inhibitory activity towards 3CLpro enzymatic activity. The selected compounds were then tested in vitro for their cytotoxicity, for antiviral activity against SARS-CoV-2, and the replication of other coronaviruses in different cell lines. Our results showed that Baicalein (100 μg/mL) exerted strong 3CLpro activity inhibition (>90%), whereas Hispidulin and Morin displayed partial inhibition. Moreover, Baicalein, up to 25 μg/mL, hindered >50% of SARS-CoV-2 replication in Vero E6 cultures. Lastly, Baicalein displayed antiviral activity against alphacoronavirus (Feline-CoV) and betacoronavirus (Bovine-CoV and HCoV-OC43) in the cell lines. Our study confirmed the antiviral activity of Baicalein against SARS-CoV-2 and demonstrated clear evidence of its pan-coronaviral activity.
Language	English
Publishing date	2023-01-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11020314
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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: High frequency of neutralizing antibodies to type I Interferon in HIV-1 patients hospitalized for COVID-19.

Scordio, Mirko / Frasca, Federica / Santinelli, Letizia / Sorrentino, Leonardo / Pierangeli, Alessandra / Turriziani, Ombretta / Mastroianni, Claudio M / Antonelli, Guido / Viscidi, Raphael P / d'Ettorre, Gabriella / Scagnolari, Carolina

Clinical immunology (Orlando, Fla.)

2022 Volume 241, Page(s) 109068

Abstract: The presence of anti-IFN neutralizing antibodies (NAB) has been reported in critically ill COVID-19 patients. We found that 87.5% (7/8) of HIV-1 patients co-infected with SARS-CoV-2 had serum anti-IFN-I NAB against IFN-α subtypes, IFN-β and/or IFN-ω. ... ...

Abstract	The presence of anti-IFN neutralizing antibodies (NAB) has been reported in critically ill COVID-19 patients. We found that 87.5% (7/8) of HIV-1 patients co-infected with SARS-CoV-2 had serum anti-IFN-I NAB against IFN-α subtypes, IFN-β and/or IFN-ω. Anti-IFN-I NAB were also detected in oropharyngeal samples. Patients with NAB were males, and those with high serum anti-IFN-α/ω NAB titer had severe illness and exhibited reduction in the expression of IFN-stimulated genes. Thus, high titer of anti-IFN-α/ω NAB may contribute to the greater severity of COVID-19 in HIV-1 infected patients.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Female ; HIV-1 ; Humans ; Interferon Type I ; Interferon-alpha/therapeutic use ; Male ; SARS-CoV-2
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Interferon Type I ; Interferon-alpha
Language	English
Publishing date	2022-06-25
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2022.109068
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