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Article: SARS-CoV-2 Systemic Effects: New Clues.

Beltrami, Silvia / Rizzo, Sabrina / Caccuri, Francesca / Rizzo, Roberta / Bortolotti, Daria / Schiuma, Giovanna

2023 Volume 11, Issue 5

Abstract: To date, much discussion has been had on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung infection associated with COVID-19 onset, of which the major manifestation is characterized by a "cytokine storm" [ ... ]. ...

Abstract	To date, much discussion has been had on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung infection associated with COVID-19 onset, of which the major manifestation is characterized by a "cytokine storm" [...].
Language	English
Publishing date	2023-05-05
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11051209
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Innate Immune Response in SARS-CoV-2 Infection.

Schiuma, Giovanna / Beltrami, Silvia / Bortolotti, Daria / Rizzo, Sabrina / Rizzo, Roberta

Microorganisms

2022 Volume 10, Issue 3

Abstract: An efficient host immune response is crucial in controlling viral infections. Despite most studies focused on the implication of T and B cell response in COVID-19 (Corona Virus Disease-19) patients or in their activation after vaccination against SARS- ... ...

Abstract	An efficient host immune response is crucial in controlling viral infections. Despite most studies focused on the implication of T and B cell response in COVID-19 (Corona Virus Disease-19) patients or in their activation after vaccination against SARS-CoV-2, host innate immune response has raised even more interest as well. In fact, innate immunity, including Natural Killer (NK) cells, monocytes/macrophages and neutrophils, represent the first line of defense against the virus and it is essential to determine the correct activation of an efficient and specific acquired immune response. In this perspective, we will report an overview on the main findings concerning SARS-CoV-2 interaction with innate host immune system, in correlation with pathogenesis and viral immune escape mechanisms.
Language	English
Publishing date	2022-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms10030501
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Article ; Online: Innate Immune Response in SARS-CoV-2 Infection

Giovanna Schiuma / Silvia Beltrami / Daria Bortolotti / Sabrina Rizzo / Roberta Rizzo

Microorganisms, Vol 10, Iss 501, p

2022 Volume 501

Abstract	An efficient host immune response is crucial in controlling viral infections. Despite most studies focused on the implication of T and B cell response in COVID-19 (Corona Virus Disease-19) patients or in their activation after vaccination against SARS-CoV-2, host innate immune response has raised even more interest as well. In fact, innate immunity, including Natural Killer (NK) cells, monocytes/macrophages and neutrophils, represent the first line of defense against the virus and it is essential to determine the correct activation of an efficient and specific acquired immune response. In this perspective, we will report an overview on the main findings concerning SARS-CoV-2 interaction with innate host immune system, in correlation with pathogenesis and viral immune escape mechanisms.
Keywords	SARS-CoV-2 ; immunity ; innate immune cells ; immune-evasion ; natural killer cells ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Gestational Viral Infections: Role of Host Immune System.

Beltrami, Silvia / Rizzo, Sabrina / Schiuma, Giovanna / Speltri, Giorgia / Di Luca, Dario / Rizzo, Roberta / Bortolotti, Daria

Microorganisms

2023 Volume 11, Issue 7

Abstract: Viral infections in pregnancy are major causes of maternal and fetal morbidity and mortality. Infections can develop in the neonate transplacentally, perinatally, or postnatally (from breast milk or other sources) and lead to different clinical ... ...

Abstract	Viral infections in pregnancy are major causes of maternal and fetal morbidity and mortality. Infections can develop in the neonate transplacentally, perinatally, or postnatally (from breast milk or other sources) and lead to different clinical manifestations, depending on the viral agent and the gestational age at exposure. Viewing the peculiar tolerogenic status which characterizes pregnancy, viruses could exploit this peculiar immunological status to spread or affect the maternal immune system, adopting several evasion strategies. In fact, both DNA and RNA virus might have a deep impact on both innate and acquired immune systems. For this reason, investigating the interaction with these pathogens and the host's immune system during pregnancy is crucial not only for the development of most effective therapies and diagnosis but mostly for prevention. In this review, we will analyze some of the most important DNA and RNA viruses related to gestational infections.
Language	English
Publishing date	2023-06-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11071637
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Article: In Situ Endothelial SARS-CoV-2 Presence and PROS1 Plasma Levels Alteration in SARS-CoV-2-Associated Coagulopathies.

Baroni, Marcello / Beltrami, Silvia / Schiuma, Giovanna / Ferraresi, Paolo / Rizzo, Sabrina / Passaro, Angelina / Molina, Juana Maria Sanz / Rizzo, Roberta / Di Luca, Dario / Bortolotti, Daria

Life (Basel, Switzerland)

2024 Volume 14, Issue 2

Abstract: Background: Coagulation decompensation is one of the complications most frequently encountered in COVID-19 patients with a poor prognosis or long-COVID syndrome, possibly due to the persistence of SARS-CoV-2 infection in the cardiovascular system. To ... ...

Abstract	Background: Coagulation decompensation is one of the complications most frequently encountered in COVID-19 patients with a poor prognosis or long-COVID syndrome, possibly due to the persistence of SARS-CoV-2 infection in the cardiovascular system. To date, the mechanism underlying the alteration of the coagulation cascade in COVID-19 patients remains misunderstood and the anticoagulant protein S (PROS1) has been described as a potential risk factor for complications related to COVID-19, due to PLpro SARS-CoV-2 enzyme proteolysis. Methods: Biopsies and blood samples were collected from SARS-CoV-2 positive and negative swab test subjects with coagulopathies (peripheral arterial thrombosis), and SARS-CoV-2 presence, ACE2 and CD147 expression, and plasmatic levels of PROS1 were evaluated. Results: We reported a significant decrease of plasmatic PROS1 in the coagulopathic SARS-CoV-2 swab positive cohort, in association with SARS-CoV-2 in situ infection and CD147 peculiar expression. These data suggested that SARS-CoV-2 associated thrombotic/ischemic events might involve PROS1 cleavage by viral PLpro directly in the site of infection, leading to the loss of its anticoagulant function. Conclusions: Based on this evidence, the identification of predisposing factors, such as CD147 increased expression, and the use of PLpro inhibitors to preserve PROS1 function, might be useful for COVID-19 coagulopathies management.
Language	English
Publishing date	2024-02-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life14020237
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Article ; Online: Non-classical HLA class I molecules and their potential role in viral infections.

Beltrami, Silvia / Rizzo, Sabrina / Strazzabosco, Giovanni / Gentili, Valentina / Alogna, Andrea / Narducci, Marco / Bortolotti, Daria / Schiuma, Giovanna / Rizzo, Roberta

Human immunology

2023 Volume 84, Issue 8, Page(s) 384–392

Abstract: Human Leukocyte Antigens (HLA) are classified in three different classes I, II and III, and represent the key mediators of immune responses, self-tolerance development and pathogen recognition. Among them, non-classical subtypes (HLA-Ib), e.g. HLA-E and ... ...

Abstract	Human Leukocyte Antigens (HLA) are classified in three different classes I, II and III, and represent the key mediators of immune responses, self-tolerance development and pathogen recognition. Among them, non-classical subtypes (HLA-Ib), e.g. HLA-E and HLA-G, are characterize by tolerogenic functions that are often exploited by viruses to evade the host immune responses. In this perspective, we will review the main current data referred to HLA-G and HLA-E and viral infections, as well as the impact on immune response. Data were selected following eligibility criteria accordingly to the reviewed topic. We used a set of electronic databases (Medline/PubMed, Scopus, Web of Sciences (WOS), Cochrane library) for a systematic search until November 2022 using MeSH keywords/terms (i.e. HLA, HLA-G, HLA-E, viral infection, SARS-CoV-2, etc.…). Recent studies support the involvement of non-classical molecules, such as HLA-E and HLA-G, in the control of viral infection. On one side, viruses exploit HLA-G and HLA-E molecule to control host immune activation. On the other side, the expression of these molecules might control the inflammatory condition generated by viral infections. Hence, this review has the aim to summarize the state of art of literature about the modulation of these non-classical HLA-I molecules, to provide a general overview of the new strategies of viral immune system regulation to counteract immune defenses.
MeSH term(s)	Humans ; HLA-G Antigens ; SARS-CoV-2 ; COVID-19 ; Histocompatibility Antigens Class I ; HLA Antigens/genetics ; Virus Diseases
Chemical Substances	HLA-G Antigens ; Histocompatibility Antigens Class I ; HLA Antigens
Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2023.03.007
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Article: Innate Immune Response in SARS-CoV-2 Infection

Schiuma, Giovanna / Beltrami, Silvia / Bortolotti, Daria / Rizzo, Sabrina / Rizzo, Roberta

Microorganisms. 2022 Feb. 23, v. 10, no. 3

2022

Abstract	An efficient host immune response is crucial in controlling viral infections. Despite most studies focused on the implication of T and B cell response in COVID-19 (Corona Virus Disease-19) patients or in their activation after vaccination against SARS-CoV-2, host innate immune response has raised even more interest as well. In fact, innate immunity, including Natural Killer (NK) cells, monocytes/macrophages and neutrophils, represent the first line of defense against the virus and it is essential to determine the correct activation of an efficient and specific acquired immune response. In this perspective, we will report an overview on the main findings concerning SARS-CoV-2 interaction with innate host immune system, in correlation with pathogenesis and viral immune escape mechanisms.
Keywords	B-lymphocytes ; COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; adaptive immunity ; immune response ; innate immunity ; macrophages ; monocytes ; neutrophils ; pathogenesis ; vaccination ; viruses
Language	English
Dates of publication	2022-0223
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms10030501
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Dihydroartemisinin-Ursodeoxycholic Bile Acid Hybrids in the Fight against SARS-CoV-2.

Marchesi, Elena / Gentili, Valentina / Bortolotti, Daria / Preti, Lorenzo / Marchetti, Paolo / Cristofori, Virginia / Fantinati, Anna / Rizzo, Roberta / Trapella, Claudio / Perrone, Daniela / Navacchia, Maria Luisa

ACS omega

2023 Volume 8, Issue 47, Page(s) 45078–45087

Abstract: Here, we propose the molecular hybridization of dihydroartemisinin (DHA) and ursodeoxycholic bile acid (UDCA), approved drugs, for the preparation of antiviral agents against SARS-CoV-2. DHA and UDCA were selected on the basis of their recently ... ...

Abstract	Here, we propose the molecular hybridization of dihydroartemisinin (DHA) and ursodeoxycholic bile acid (UDCA), approved drugs, for the preparation of antiviral agents against SARS-CoV-2. DHA and UDCA were selected on the basis of their recently demonstrated
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.3c07034
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway.

Bortolotti, Daria / Gentili, Valentina / Rizzo, Sabrina / Rotola, Antonella / Rizzo, Roberta

Cells

2020 Volume 9, Issue 9

Abstract: Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV ...

Abstract	Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV and SARS-CoV-2 naïve subjects were evaluated for their activation, degranulation, and interferon-gamma expression in the presence of SARS-CoV and SARS-CoV-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune fluorescence. SARS-CoV and SARS-CoV-2 spike proteins did not alter NK cell activation in a K562 in vitro model. On the contrary, SARS-CoV-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell-reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of an SP1-derived HLA-E-binding peptide. Simultaneously, there was increased modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 was expressed in lung epithelial cells. We ruled out the GATA3 transcription factor as being responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicated in NK cell exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells' exhaustion might contribute to immunopathogenesis in SARS-CoV-2 infection.
MeSH term(s)	Betacoronavirus/chemistry ; Blood Donors ; Bronchi/cytology ; COVID-19 ; Cell Degranulation/genetics ; Coculture Techniques ; Coronavirus Infections/immunology ; Coronavirus Infections/metabolism ; Coronavirus Infections/virology ; Epithelial Cells/metabolism ; Histocompatibility Antigens Class I/metabolism ; Humans ; Interferon-gamma/metabolism ; K562 Cells ; Killer Cells, Natural/immunology ; Lymphocyte Activation/genetics ; NK Cell Lectin-Like Receptor Subfamily C/metabolism ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/virology ; RNA, Viral/genetics ; Severe acute respiratory syndrome-related coronavirus/chemistry ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome/immunology ; Severe Acute Respiratory Syndrome/metabolism ; Severe Acute Respiratory Syndrome/virology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Transfection ; HLA-E Antigens
Chemical Substances	Histocompatibility Antigens Class I ; IFNG protein, human ; KLRC1 protein, human ; NK Cell Lectin-Like Receptor Subfamily C ; RNA, Viral ; Spike Glycoprotein, Coronavirus ; spike glycoprotein, SARS-CoV ; spike protein, SARS-CoV-2 ; Interferon-gamma (82115-62-6)
Keywords	covid19
Language	English
Publishing date	2020-08-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9091975
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Article ; Online: COVID-19 induced aorto duodenal fistula following evar in the so called "negative" patient.

Traina, Luca / Mucignat, Marianna / Rizzo, Roberta / Gafà, Roberta / Bortolotti, Daria / Passaro, Angelina / Zamboni, Paolo

Vascular

2021 Volume 31, Issue 1, Page(s) 189–195

Abstract: Objectives: Since October 2019, SARS-CoV-2 pandemic represents a challenge for the international healthcare system and for the treatment and survival of patients. We normally focus on symptomatic patients, and symptoms can range from the respiratory to ... ...

Abstract	Objectives: Since October 2019, SARS-CoV-2 pandemic represents a challenge for the international healthcare system and for the treatment and survival of patients. We normally focus on symptomatic patients, and symptoms can range from the respiratory to the gastrointestinal system. In addition, we consider patients without fever and respiratory symptoms, with both a negative RT nasopharyngeal swab and lung CT, as a "Covid-19 negative patient." In this article, we present a so called Covid-19 "negative" patient, with an unsuspected vascular clinical onset of the viral infection. Methods: An 80 y.o. man, who previously underwent endovascular aortic repair for an infrarenal abdominal aortic aneurysm, presented to our department with an atypical presentation of an aorto-enteric fistula during the pandemic. While in hospital, weekly nasopharyngeal swab tests were always negative for SARS-CoV-2. However, the absence of aortic endograft complications, the gross anatomy of duodenal ischemic injury, and the recent history of the patient who lived the last months in Bergamo, the Italian city with the highest number of COVID-19 deaths, lead the senior Author to suspect an occult SARS-CoV-2 infection. The patient underwent to resection of the fourth portion of the duodenum and the first jejunal loop, with subsequent duodenum-jejunal latero-lateral anastomosis and the direct suture of the aortic wall. The intestinal specimen was investigated as suspected SARS-CoV-2 bowel infection by the means of immune-histochemistry (IHC). An ileum sample obtained in the pre-COVID-19 era was used as a control tissue. Results: The histological analysis of the bowel revealed sustained wall ischemia and liponecrosis of the duodenal wall, with intramural blood vessels thrombosis. Blood vessel endotheliitis and neo-angiogenesis were also observed. Finally, the IHC was strongly positive for SARS-CoV-2 RNA and for HLA-G presence, with a particular concentration both in blood vessels and in the intestinal villi. The control tissue sample was not positive for both SARS-CoV-2 and HLA-G. Conclusions: Coronavirus pandemic continues to be an international challenge and more studies and trials must be done to learn its pathogenesis and its complications. As for thromboembolic events caused by SARS-COV-2, vascular surgeons are involved in treatment and prevention of the complications of this syndrome and must be ready with general surgeons to investigate atypical and particular cases such as the one discussed in this article.
MeSH term(s)	Male ; Humans ; COVID-19 ; SARS-CoV-2 ; HLA-G Antigens ; RNA, Viral ; Ischemia ; Fistula
Chemical Substances	HLA-G Antigens ; RNA, Viral
Language	English
Publishing date	2021-12-17
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2137151-9
ISSN	1708-539X ; 1708-5381
ISSN (online)	1708-539X
ISSN	1708-5381
DOI	10.1177/17085381211053695
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