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3. Humoral and T-Cell Immune Response After 3 Doses of Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines in Fragile Patients: The Italian VAX4FRAIL Study

Author

Corradini, P., Agrati, C., Apolone, G., Mantovani, A., Giannarelli, D., Marasco, V., Bordoni, V., Sacchi, A., Matusali, G., Salvarani, C., Zinzani, P. L., Mantegazza, R., Tagliavini, F., Lupo-Stanghellini, M. T., Ciceri, F., Damian, S., Uccelli, A., Fenoglio, D., Silvestris, N., Baldanti, F., Piaggio, G., Ciliberto, G., Morrone, A., Locatelli, Franco, Sinno, V., Rescigno, M., Costantini, M., Locatelli F. (ORCID:0000-0002-7976-3654), Corradini, P., Agrati, C., Apolone, G., Mantovani, A., Giannarelli, D., Marasco, V., Bordoni, V., Sacchi, A., Matusali, G., Salvarani, C., Zinzani, P. L., Mantegazza, R., Tagliavini, F., Lupo-Stanghellini, M. T., Ciceri, F., Damian, S., Uccelli, A., Fenoglio, D., Silvestris, N., Baldanti, F., Piaggio, G., Ciliberto, G., Morrone, A., Locatelli, Franco, Sinno, V., Rescigno, M., Costantini, M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

BACKGROUND: Patients with solid or hematological tumors or neurological and immune-inflammatory disorders are potentially fragile subjects at increased risk of experiencing severe coronavirus disease 2019 and an inadequate response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: We designed a prospective Italian multicenter study to assess humoral and T-cell responses to SARS-CoV-2 vaccination in patients (n = 378) with solid tumors (ST), hematological malignancies (HM), neurological disorders (ND), and immunorheumatological diseases (ID). A group of healthy controls was also included. We analyzed the immunogenicity of the primary vaccination schedule and booster dose. RESULTS: The overall seroconversion rate in patients after 2 doses was 62.1%. Significantly lower rates were observed in HM (52.4%) and ID (51.9%) than in ST (95.6%) and ND (70.7%); a lower median antibody level was detected in HM and ID versus ST and ND (P < .0001). Similar rates of patients with a positive SARS-CoV-2 T-cell response were found in all disease groups, with a higher level observed in ND. The booster dose improved the humoral response in all disease groups, although to a lesser extent in HM patients, whereas the T-cell response increased similarly in all groups. In the multivariable logistic model, independent predictors of seroconversion were disease subgroup, treatment type, and age. Ongoing treatment known to affect the immune system was associated with the worst humoral response to vaccination (P < .0001) but had no effect on T-cell responses. CONCLUSIONS: Immunosuppressive treatment more than disease type per se is a risk factor for a low humoral response after vaccination. The booster dose can improve both humoral and T-cell responses.

Published
2023

4. Inflammatory and senescence-associated mediators affect the persistence of humoral response to COVID-19 mRNA vaccination in transfusion-dependent beta-thalassemic patients

Author

Bordoni, V., Casale, M., Pinto, V. M., Carsetti, R., Gianesin, B., Gamberini, M. R., Mazdai, L., Barella, S., Denotti, A. R., Colavita, F., Perrotta, S., Maggio, A., Pitrolo, L., Quintino, S., Caminati, M., Mazzi, F., Ceolan, J., De Franceschi, L., Forni, G. L., Locatelli, Franco, Agrati, C., Locatelli F. (ORCID:0000-0002-7976-3654), Bordoni, V., Casale, M., Pinto, V. M., Carsetti, R., Gianesin, B., Gamberini, M. R., Mazdai, L., Barella, S., Denotti, A. R., Colavita, F., Perrotta, S., Maggio, A., Pitrolo, L., Quintino, S., Caminati, M., Mazzi, F., Ceolan, J., De Franceschi, L., Forni, G. L., Locatelli, Franco, Agrati, C., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

N/A

Published
2023

5. Emerging viral infections in immunocompromised patients: A great challenge to better define the role of immune response

Author

Agrati, C., Bartolini, B., Bordoni, V., Locatelli, Franco, Capobianchi, M. R., Di Caro, A., Castilletti, C., Ippolito, G., Locatelli F. (ORCID:0000-0002-7976-3654), Agrati, C., Bartolini, B., Bordoni, V., Locatelli, Franco, Capobianchi, M. R., Di Caro, A., Castilletti, C., Ippolito, G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

The immune response to invading pathogens is characterized by the rapid establishment of a complex network of cellular interactions and soluble signals. The correct balancing of activating and regulating pathways and tissue-homing signals determines its effectiveness and persistence over time. Emerging viral pathogens have always represented a great challenge to the immune system and an often uncontrolled/imbalanced immune response has been described (e.g. cytokine storm, immune paralysis), contributing to the severity of the disease. Several immune biomarkers and cell subsets have been identified as major players in the cascade of events leading to severe diseases, highlighting the rationale for host-directed intervention strategy. There are millions of immunocompromised pediatric and adult patients worldwide (e.g. transplant recipients, hematologic patients, subjects with primary immune-deficiencies), experiencing an impaired immune reactivity, due to diseases and/or to the medical treatments. The reduced immune reactivity could have two paradoxical non-exclusive effects: a weak protective immunity on one hand, and a reduced contribution to immune-mediated pathogenetic processes on the other hand. In these sensitive contexts, the impact of emerging infections represents a still open issue to be explored with several challenges for immunologists, virologists, physicians and epidemiologists. In this review, we will address emerging infections in immunocompromised hosts, to summarize the available data concerning the immune response profile, its influence on the clinical presentation, the possible contribution of persistent viral shedding in generating new viral variants with improved immune escape features, and the key role of vaccination.

Published
2023

6. The immune response as a double-edged sword: The lesson learnt during the COVID-19 pandemic

Author

Agrati, C., Carsetti, R., Bordoni, V., Sacchi, A., Quintarelli, C., Locatelli, Franco, Ippolito, G., Capobianchi, M. R., Locatelli F. (ORCID:0000-0002-7976-3654), Agrati, C., Carsetti, R., Bordoni, V., Sacchi, A., Quintarelli, C., Locatelli, Franco, Ippolito, G., Capobianchi, M. R., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

The COVID-19 pandemic has represented an unprecedented challenge for the humanity, and scientists around the world provided a huge effort to elucidate critical aspects in the fight against the pathogen, useful in designing public health strategies, vaccines and therapeutic approaches. One of the first pieces of evidence characterizing the SARS-CoV-2 infection has been its breadth of clinical presentation, ranging from asymptomatic to severe/deadly disease, and the indication of the key role played by the immune response in influencing disease severity. This review is aimed at summarizing what the SARS-CoV-2 infection taught us about the immune response, highlighting its features of a double-edged sword mediating both protective and pathogenic processes. We will discuss the protective role of soluble and cellular innate immunity and the detrimental power of a hyper-inflammation-shaped immune response, resulting in tissue injury and immunothrombotic events. We will review the importance of B- and T-cell immunity in reducing the clinical severity and their ability to cross-recognize viral variants.

Published
2022

7. The BNT162b2 vaccine induces humoral and cellular immune memory to SARS-CoV-2 Wuhan strain and the Omicron variant in children 5 to 11 years of age

Author

Cinicola, B. L., Piano Mortari, E., Zicari, A. M., Agrati, C., Bordoni, V., Albano, C., Fedele, G., Schiavoni, I., Leone, P., Fiore, S., Capponi, M., Conti, M. G., Petrarca, L., Stefanelli, P., Spalice, A., Midulla, F., Palamara, A. T., Quinti, I., Locatelli, Franco, Carsetti, R., Locatelli F. (ORCID:0000-0002-7976-3654), Cinicola, B. L., Piano Mortari, E., Zicari, A. M., Agrati, C., Bordoni, V., Albano, C., Fedele, G., Schiavoni, I., Leone, P., Fiore, S., Capponi, M., Conti, M. G., Petrarca, L., Stefanelli, P., Spalice, A., Midulla, F., Palamara, A. T., Quinti, I., Locatelli, Franco, Carsetti, R., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

SARS-CoV-2 mRNA vaccines prevent severe COVID-19 by generating immune memory, comprising specific antibodies and memory B and T cells. Although children are at low risk of severe COVID-19, the spreading of highly transmissible variants has led to increasing in COVID-19 cases and hospitalizations also in the youngest, but vaccine coverage remains low. Immunogenicity to mRNA vaccines has not been extensively studied in children 5 to 11 years old. In particular, cellular immunity to the wild-type strain (Wuhan) and the cross-reactive response to the Omicron variant of concern has not been investigated. We assessed the humoral and cellular immune response to the SARS-CoV-2 BNT162b2 vaccine in 27 healthy children. We demonstrated that vaccination induced a potent humoral and cellular immune response in all vaccinees. By using spike-specific memory B cells as a measurable imprint of a previous infection, we found that 50% of the children had signs of a past, undiagnosed infection before vaccination. Children with pre-existent immune memory generated significantly increased levels of specific antibodies, and memory T and B cells, directed against not only the wild type virus but also the omicron variant.

Published
2022

8. Elevated P-selectin in severe Covid-19: Considerations for therapeutic options

Author

Agrati C., Bordoni V., Sacchi A., Petrosillo N., Nicastri E., Del Nonno F., D'Offizi G., Palmieri F., Marchioni L., Capobianchi M. R., Antinori A., Ippolito G., Bibas M., Agrati, C., Bordoni, V., Sacchi, A., Petrosillo, N., Nicastri, E., Del Nonno, F., D'Offizi, G., Palmieri, F., Marchioni, L., Capobianchi, M. R., Antinori, A., Ippolito, G., and Bibas, M.

Subjects
Platelets, Endothelium, P-selectin, Covid-19
Abstract

Background: Coronavirus disease 2019 (COVID-19) is mainly a respiratory tract disease and acute respiratory failure with diffuse microvascular pulmonary thrombosis are critical aspects of the morbidity and mortality of this new syndrome. Purpose: The aim of our study was to investigate, in severe COVID-19 hospitalized patients, the P-selectin plasma concentration as a biomarker of endothelial dysfunction and platelet activation. Methods: 46 patients with severe or critical SARS-CoV-2 infection were included in the study. Age-matched patients then were divided in those requiring admission to the intensive care unit (ICU, ICU cases) vs those not requiring ICU hospitalization (non-ICU cases). Blood samples of severe COVID-19 patients were collected at the time of hospital admission. The quantification of soluble P-selectin was performed by ELI, assay. Results: Our study showed a higher P-selectin plasma concentration in patients with Covid-19, regardless of ICU admission, compared to the normal reference values and compared to ten contextually sampled healthy donors (HD); (COVID-19): median 65.2 (IQRs: 45.1-81.1) vs. HD: 40.3 (IQRs: 24.3-48.7), p=0023. Moreover, results showed a significant reduction of P-sele din after platelets removal in HD, in contrast, both ICU and non-ICU COVID-19 patients showed similar high levels of P-selectin with and without platelets. Conclusion: Elevation of P-selectin suggests a central role of platelet endothelium interaction as part of the multifaced pathogenic mechanism of COVID-19 leading to the local activation of hemostatic system forming pulmonary thrombi. Further work is necessary to determine the therapeutic role of antiplatelets agents or of the anti P-selectin antibody Crizanlizumab.

Published
2021

9. Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia

Author

Vergori, A., Lorenzini, P., Cozzi-Lepri, A., Donno, D. R., Gualano, G., Nicastri, E., Iacomi, F., Marchioni, L., Campioni, P., Schinina, V., Cicalini, S., Agrati, C., Capobianchi, M. R., Girardi, E., Ippolito, G., Vaia, F., Petrosillo, N., Antinori, A., Taglietti, F., The ReCOVeRI Study Group: Abbonizio, M. A., Abdeddaim, A., Agostini, E., Albarello, F., Amadei, G., Amendola, A., Antonica, M. A., Antonini, M., Bartoli, T. A., Baldini, F., Barbaro, R., Bartolini, B., Bellagamba, R., Benigni, M., Bevilacqua, N., Biava, G., Bibas, M., Bordi, L., Bordoni, V., Boumis, E., Branca, M., Buonomo, R., Busso, D., Camici, M., Canichella, F., Capone, A., Caporale, C., Caraffa, E., Caravella, I., Carletti, F., Castilletti, C., Cataldo, A., Cerilli, S., Cerva, C., Chiappini, R., Chinello, P., Cianfarani, M. A., Ciaralli, C., Cimaglia, C., Cinicola, N., Ciotti, V., Colavita, F., Corpolongo, A., Cristofaro, M., Curiale, S., D'Abramo, A., Dantimi, C., De Angelis, A., De Angelis, G., De Palo, M. G., De Zottis, F., Di Bari, V., Di Lorenzo, R., Di Stefano, F., D'Offizi, G., Evangelista, F., Faraglia, F., Farina, A., Ferraro, F., Fiorentini, L., Frustaci, A., Fusetti, M., Fusto, M., Galati, V., Gagliardini, R., Galli, P., Garotto, G., Gaviano, I., Tekle, S. G., Giancola, M. L., Giansante, F., Giombini, E., Granata, G., Greci, M. C., Grilli, E., Grisetti, S., Iaconi, M., Iannicelli, G., Inversi, C., Lalle, E., Lamanna, M. E., Lanini, S., Lapa, D., Lepore, L., Libertone, R., Lionetti, R., Liuzzi, G., Loiacono, L., Lucia, A., Lufrani, F., Macchione, M., Maffongelli, G., Marani, A., Mariano, A., Marini, M. C., Maritti, M., Mastrobattista, A., Mastrorosa, I., Matusali, G., Mazzotta, V., Mencarini, P., Meschi, S., Messina, F., Micarelli, S., Mogavero, G., Mondi, A., Montalbano, M., Montaldo, C., Mosti, S., Murachelli, S., Musso, M., Nardi, M., Navarra, A., Nocioni, M., Noto, P., Noto, R., Oliva, A., Onnis, I., Ottou, S., Palazzolo, C., Pallini, E., Palmieri, F., Palombi, G., Pareo, C., Passeri, V., Pelliccioni, F., Penna, G., Petrecchia, A., Petrone, A., Pianura, E., Pinnetti, C., Pisciotta, M., Piselli, P., Pittalis, S., Pontarelli, A., Proietti, C., Puro, V., Ramazzini, P. M., Rianda, A., Rinonapoli, G., Rosati, S., Rubino, D., Rueca, M., Ruggeri, A., Sacchi, A., Sampaolesi, A., Sanasi, F., Santagata, C., Scarabello, A., Scarcia, S., Scognamiglio, P., Scorzolini, L., Stazi, G., Strano, G., Taibi, C., Taloni, G., Nardi, T., Tonnarini, R., Topino, S., Tozzi, M., Vairo, F., Valli, M. B., Vincenzi, L., Visco-Comandini, U., Vita, S., Vittozzi, P., Zaccarelli, M., Zanetti, A., Zito, S., Vergori, A., Lorenzini, P., Cozzi-Lepri, A., Donno, D. R., Gualano, G., Nicastri, E., Iacomi, F., Marchioni, L., Campioni, P., Schinina, V., Cicalini, S., Agrati, C., Capobianchi, M. R., Girardi, E., Ippolito, G., Vaia, F., Petrosillo, N., Antinori, A., Taglietti, F., Abbonizio, M. A., Abdeddaim, A., Agostini, E., Albarello, F., Amadei, G., Amendola, A., Antonica, M. A., Antonini, M., Bartoli, T. A., Baldini, F., Barbaro, R., Bartolini, B., Bellagamba, R., Benigni, M., Bevilacqua, N., Biava, G., Bibas, M., Bordi, L., Bordoni, V., Boumis, E., Branca, M., Buonomo, R., Busso, D., Camici, M., Canichella, F., Capone, A., Caporale, C., Caraffa, E., Caravella, I., Carletti, F., Castilletti, C., Cataldo, A., Cerilli, S., Cerva, C., Chiappini, R., Chinello, P., Cianfarani, M. A., Ciaralli, C., Cimaglia, C., Cinicola, N., Ciotti, V., Colavita, F., Corpolongo, A., Cristofaro, M., Curiale, S., D'Abramo, A., Dantimi, C., De Angelis, A., De Angelis, G., De Palo, M. G., De Zottis, F., Di Bari, V., Di Lorenzo, R., Di Stefano, F., D'Offizi, G., Evangelista, F., Faraglia, F., Farina, A., Ferraro, F., Fiorentini, L., Frustaci, A., Fusetti, M., Fusto, M., Galati, V., Gagliardini, R., Galli, P., Garotto, G., Gaviano, I., Tekle, S. G., Giancola, M. L., Giansante, F., Giombini, E., Granata, G., Greci, M. C., Grilli, E., Grisetti, S., Iaconi, M., Iannicelli, G., Inversi, C., Lalle, E., Lamanna, M. E., Lanini, S., Lapa, D., Lepore, L., Libertone, R., Lionetti, R., Liuzzi, G., Loiacono, L., Lucia, A., Lufrani, F., Macchione, M., Maffongelli, G., Marani, A., Mariano, A., Marini, M. C., Maritti, M., Mastrobattista, A., Mastrorosa, I., Matusali, G., Mazzotta, V., Mencarini, P., Meschi, S., Messina, F., Micarelli, S., Mogavero, G., Mondi, A., Montalbano, M., Montaldo, C., Mosti, S., Murachelli, S., Musso, M., Nardi, M., Navarra, A., Nocioni, M., Noto, P., Noto, R., Oliva, A., Onnis, I., Ottou, S., Palazzolo, C., Pallini, E., Palmieri, F., Palombi, G., Pareo, C., Passeri, V., Pelliccioni, F., Penna, G., Petrecchia, A., Petrone, A., Pianura, E., Pinnetti, C., Pisciotta, M., Piselli, P., Pittalis, S., Pontarelli, A., Proietti, C., Puro, V., Ramazzini, P. M., Rianda, A., Rinonapoli, G., Rosati, S., Rubino, D., Rueca, M., Ruggeri, A., Sacchi, A., Sampaolesi, A., Sanasi, F., Santagata, C., Scarabello, A., Scarcia, S., Scognamiglio, P., Scorzolini, L., Stazi, G., Strano, G., Taibi, C., Taloni, G., Nardi, T., Tonnarini, R., Topino, S., Tozzi, M., Vairo, F., Valli, M. B., Vincenzi, L., Visco-Comandini, U., Vita, S., Vittozzi, P., Zaccarelli, M., Zanetti, A., and Zito, S.

Subjects
Male, medicine.medical_treatment, Rome, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Severity of Illness Index, 0302 clinical medicine, Retrospective Studie, Coagulopathy, Clinical endpoint, Intubation, Respiratory function, 030212 general & internal medicine, Multidisciplinary, Middle Aged, Medicine, Female, Human, medicine.medical_specialty, Patients, medicine.drug_class, Science, Low molecular weight heparin, Risk Assessment, Article, NO, 03 medical and health sciences, Internal medicine, Severity of illness, medicine, Intubation, Intratracheal, Humans, Retrospective Studies, Aged, business.industry, SARS-CoV-2, COVID-19, Thrombocytopenia, Retrospective cohort study, Heparin, Low-Molecular-Weight, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, respiratory tract diseases, Pneumonia, Viral infection, business
Abstract

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50–77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2–26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7–15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51–3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03–2.18) for those with PaO2/FiO2 > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

Published
2021

10. SARS-CoV-2 isolation from ocular secretions of a patient with COVID-19 in Italy with prolonged viral RNA detection

Author

Colavita F., Lapa D., Carletti F., Lalle E., Bordi L., Marsella P., Nicastri E., Bevilacqua N., Giancola M. L., Corpolongo A., Ippolito G., Capobianchi M. R., Castilletti C., Abbonizio M. A., Agrati C., Albarello F., Amadei G., Amendola A., Antonini M., Barbaro R., Bartolini B., Benigni M., Bordoni V., Branca M., Campioni P., Caporale C., Caravella I., Chiappini R., Ciaralli C., Cristofaro M., Curiale S., D'Abramo A., Dantimi C., de Angelis A., de Angelis G., Di Lorenzo R., Di Stefano F., Ferraro F., Fiorentini L., Frustaci A., Galli P., Garotto G., Giansante F., Giombini E., Greci M. C., Lanini S., Lepore L., Lucia A., Lufrani F., Macchione M., Marani A., Marchioni L., Mariano A., Marini M. C., Maritti M., Matusali G., Meschi S., Messina F., Montaldo C., Murachelli S., Noto R., Palazzolo C., Pallini E., Passeri V., Pelliccioni F., Petrecchia A., Petrone A., Petrosillo N., Pianura E., Pisciotta M., Pittalis S., Proietti C., Puro V., Rinonapoli G., Rueca M., Sacchi A., Sanasi F., Santagata C., Scarcia S., Schinina V., Scognamiglio P., Scorzolini L., Stazi G., Vaia F., Vairo F., Valli M. B., Colavita, F., Lapa, D., Carletti, F., Lalle, E., Bordi, L., Marsella, P., Nicastri, E., Bevilacqua, N., Giancola, M. L., Corpolongo, A., Ippolito, G., Capobianchi, M. R., Castilletti, C., Abbonizio, M. A., Agrati, C., Albarello, F., Amadei, G., Amendola, A., Antonini, M., Barbaro, R., Bartolini, B., Benigni, M., Bordoni, V., Branca, M., Campioni, P., Caporale, C., Caravella, I., Chiappini, R., Ciaralli, C., Cristofaro, M., Curiale, S., D'Abramo, A., Dantimi, C., de Angelis, A., de Angelis, G., Di Lorenzo, R., Di Stefano, F., Ferraro, F., Fiorentini, L., Frustaci, A., Galli, P., Garotto, G., Giansante, F., Giombini, E., Greci, M. C., Lanini, S., Lepore, L., Lucia, A., Lufrani, F., Macchione, M., Marani, A., Marchioni, L., Mariano, A., Marini, M. C., Maritti, M., Matusali, G., Meschi, S., Messina, F., Montaldo, C., Murachelli, S., Noto, R., Palazzolo, C., Pallini, E., Passeri, V., Pelliccioni, F., Petrecchia, A., Petrone, A., Petrosillo, N., Pianura, E., Pisciotta, M., Pittalis, S., Proietti, C., Puro, V., Rinonapoli, G., Rueca, M., Sacchi, A., Sanasi, F., Santagata, C., Scarcia, S., Schinina, V., Scognamiglio, P., Scorzolini, L., Stazi, G., Vaia, F., Vairo, F., and Valli, M. B.

Subjects
Isolation (health care), Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Eye, NO, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, Medicine, Viral rna, 030304 developmental biology, 0303 health sciences, SARS-CoV-2, business.industry, COVID-19, RNA, Pneumonia, General Medicine, Conjunctivitis, medicine.disease, Letters: Observations, Virology, 3. Good health, Viral replication, 030221 ophthalmology & optometry, business, Viral load, COVID-19, Conjunctivitis, Eye, Pneumonia, SARS-CoV-2
Abstract

Background: Coronavirus disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in China in December 2019, was recently recognized as pandemic threat by the World Health Organization, with the potential of rapidly overloading health care systems and causing substantial mortality worldwide (www.who.int/dg/speeches/detail/who-director-general -s-opening-remarks-at-the-media-briefing-on-covid-19 —11-march -2020). Human-to-human transmission occurs mainly through respiratory droplets, but other routes are under investigation, because SARS-CoV-2 has been detected in several body fluids (1). So far, few data are available on ocular samples from patients with COVID-19, although conjunctivitis has been occasionally reported among COVID-19 symptoms, similar to infections caused by other human coronaviruses (2, 3). During the SARS epidemic, eye exposure to infectious fluids was associated with an increased risk for SARS-CoV transmission to health care workers (3, 4). Although SARS-CoV RNA was occasionally found in ocular specimens during the early phase of illness, its infectivity is unknown (2, 3). With regard to COVID-19, unprotected ocular exposure was thought to be responsible for infections that occurred in the Wuhan Fever Clinic in January 2020 (3, 4); in addition, SARS-CoV-2 RNA was detected in conjunctival secretions collected from the only patient with conjunctivitis out of 30 patients with COVID-19 from a hospital in China (5). However, further studies are needed to evaluate the infectious potential of the SARS-CoV-2 RNA detected in the ocular specimens and to determine whether transmission may occur through ocular secretions (3, 4). Objective: To present the early detection of infectious SARS-CoV-2 in ocular fluids from a patient with the first confirmed case of COVID-19 in Italy, who had been hospitalized at the National Institute for Infectious Diseases “L. Spallanzani” (INMI) in Rome. Methods and Findings: The patient, a 65-year-old woman, travelled from Wuhan, China, to Italy on 23 January 2020 and was admitted on 29 January 2020, 1 day after symptom onset. At admission to the high isolation unit at INMI, she presented with nonproductive cough, sore throat, coryza, and bilateral conjunctivitis. She had no fever until day 4, when fever (38 °C), nausea, and vomiting began. Infection with SARS-CoV-2 was confirmed by performing real-time reverse transcription polymerase chain reaction (RT-PCR) assay on sputum samples (cycle threshold value [Ct], 16.1) on the admission day, followed by viral M gene sequencing (GenBank accession number MT008022), and virus isolation on Vero E6 cell line (2019-nCoV/Italy-INMI1). The full genome sequence was obtained from either clinical sample or culture isolate (GISAID accession numbers EPI_ISL_410545 and EPI_ISL_410546). At admission, no other respiratory infections were detected (QIAstat-Dx Respiratory Panel; Qiagen).

Published
2020

11. Synergy between vitamin D and sex hormones in respiratory functionality of patients affected by COVID-19

Author

Peruzzu, D., Pagano, M. T., Pierdominici, M., Ruggieri, A., Antinori, A., D'Offizi, G., Petrosillo, N., Palmieri, F., Piselli, P., Boumis, E., Notari, S., Nicastri, E., Agrati, C., Ippolito, G., Gagliardi, M. C., Capobianchi, M. R., Ortona, E., Anticoli, S., Bellenghi, M., Bordoni, V., Camici1, M., Casetti, R., Cerva, C., Chinello, P., Imini, E., Donno, D. R., Dupuis, M. L., Faraglia, F., Fecchi, K., Gagliardini, R., Grassi, G., Di Lorenzo, R., Macchione, M., Maffongelli, G., Mattia, G., Milozzi, E., Pontecorvi, G., Puglisi, R., Sacchi, A., Tartaglia, E., and Vita, S.

Subjects
0301 basic medicine, sex differences, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Population, Physiology, vitamin D, RM1-950, sex hormones, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, Vitamin D and neurology, gender, Medicine, Pharmacology (medical), Respiratory system, education, Testosterone, Pharmacology, education.field_of_study, 030219 obstetrics & reproductive medicine, business.industry, SARS-CoV-2, Plasma levels, 030104 developmental biology, Perspective, Therapeutics. Pharmacology, business, Hormone
Abstract

The outcome of COVID-19 appears to be influenced by vitamin D status of population. Although epidemiological data indicate that COVID-19 produces more severe symptoms and higher mortality in elderly in comparison to young patients and in men in comparison to women to date sex and age differences in vitamin D status in infected patients have not been evaluated yet. In this study we evaluated the levels of circulating 25(OH)D in patients hospitalized for COVID-19 divided accordingly to their sex and age. We also correlated 25(OH)D levels with patient’s respiratory status (i.e., PaO2/FiO2 ratio) and with sex hormones plasma levels to analyze the potential relationship of these parameters. We found no significant differences in plasma levels of 25(OH)D between pre- and post-menopausal female patients and age matched male patients. Interestingly, the 25(OH)D plasma levels positively correlated to PaO2/FiO2 ratio only in young patients, regardless of their sex. We also found a significantly positive correlation between 17β-estradiol and 25(OH)D in elderly women and between testosterone and 25(OH)D in elderly men, supporting the role of sex hormones in maintaining 25(OH)D levels. In conclusion, we suggest that a synergy between vitamin D and sex hormones could contribute to the age-related outcome of COVID-19.

Published
2021

12. An inflammatory profile correlates with decreased frequency of cytotoxic cells in coronavirus disease 2019

Author

Bordoni, V., Sacchi, A., Cimini, E., Notari, S., Grassi, G., Tartaglia, E., Casetti, R., Giancola, M. L., Bevilacqua, N., Maeurer, M., Zumla, A., Locatelli, Franco, De Benedetti, F., Palmieri, F., Marchioni, L., Capobianchi, M. R., D'Offizi, G., Petrosillo, N., Antinori, A., Nicastri, E., Ippolito, G., Agrati, C., Locatelli F. (ORCID:0000-0002-7976-3654), Bordoni, V., Sacchi, A., Cimini, E., Notari, S., Grassi, G., Tartaglia, E., Casetti, R., Giancola, M. L., Bevilacqua, N., Maeurer, M., Zumla, A., Locatelli, Franco, De Benedetti, F., Palmieri, F., Marchioni, L., Capobianchi, M. R., D'Offizi, G., Petrosillo, N., Antinori, A., Nicastri, E., Ippolito, G., Agrati, C., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

Published
2020

16. 'Verteporfin exhibits anti-proliferative activity in embryonal and alveolar rhabdomyosarcoma cell lines'

Author

Sanna, L, Piredda, R, Marchesi, I, Bordoni, V, Forcales, SV, Calvisi, DF, and Bagella, L

Subjects
TAZ, Anti-proliferation, Rhabdomyosarcoma, Verteporfin, YAP, Cancer
Abstract

Rhabdomyosarcoma (RMS) is a pediatric tumor, which arises from muscle precursor cells. Recently, it has been demonstrated that Hippo Pathway (Hpo), a pathway that regulates several physiological and biological features, is involved in RMS tumorigenesis. For instance, an upregulation of the Hpo downstream effector Yes-Associated Protein 1 (YAP) leads to the development of embryonal rhabdomyosarcoma (eRMS) in murine activated muscle satellite cells. On the other hand, the YAP paralog transcriptional co-activator with PDZ-binding motif (TAZ) is overexpressed in alveolar rhabdomyosarcoma (aRMS) patients with poor survival. YAP and TAZ exhibit both cytoplasmic and nuclear functions. In the nucleus, YAP binds TEADs (TEA domain family members) factors and together they constitute a complex that is able either to activate the transcription of several genes such as MYC, Tbx5 and PAX8 or to maintain the stability of others like p73. Due to the key role of YAP and TAZ in cancer, the identification and/or development of new compounds able to block their activity might be an effective antineoplastic strategy. Verteporfin (VP) is a molecule able to stop the formation of YAP/TEAD complex in the nucleus. The aim of this study is to evaluate the action of VP on RMS cell lines. This work shows that VP has an anti-proliferative activity on all RMS cell lines analyzed. Depending on RMS cell lines, VP affects cell cycle differently. Moreover, VP is able to decrease YAP protein levels, and to induce the activation of apoptosis mechanism through the cleavage of PARP-1. In addition, Annexin V assay showed the activation of apoptosis and necrosis after VP treatment. In summary, the ability of VP to disrupt RMS cell proliferation could be a novel and valuable strategy to improve the therapeutic approaches in treating rhabdomyosarcoma.

Published
2019

21. Pulse high volume hemofiltration

Author

BRENDOLAN, A., DʼINTINI, V., RICCI, Z., BONELLO, M., RATANARAT, R., SALVATORI, G., BORDONI, V., DE CAL, M., ANDRIKOS, E., and RONCO, C.

Published
2004

26. JCV-specific T-cells producing IFN-gamma are differently associated with PmL occurrence in HIV patients and liver transplant recipients

Author

Chiara Agrati, Izzo, L., Berno, G., Cimini, E., Bordoni, V., Giancola, M. L., Baldini, F., Colasanti, M., Ettorre, G. M., Izzo, P., Pugliese, F., Angrisani, M., Di Cello, P., Capobianchi, M. R., and Bolognese, A.

Subjects
Adult, Male, complications, isolation & purification, etiology, T-Lymphocytes, HIV Infections, Progressive Multifocal, HIV Infections, complications, HIV Infections, immunology, HIV Infections, surgery, HIV Infections, virology, HIV-1, genetics, HIV-1, immunology, Interferon-gamma, genetics, Interferon-gamma,immunology, JC Virus, genetics, JC Virus, immunology, JC Virus, isolation & purification, Leukoencephalopathy, Progressive Multifocal, etiology, Leukoencephalopathy, Progressive Multifocal, immunology, Leukoencephalopathy, Progressive Multifocal, virology, Liver Transplantation, T-Lymphocytes, immunology, T-Lymphocytes, virology, Transplant Recipients, surgery, immunology, Interferon-gamma, Leukoencephalopathy, Humans, genetics, Aged, Leukoencephalopathy, Progressive Multifocal, Middle Aged, JC Virus, virology, HIV-1, Female
Abstract

Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LTR.

Published
2014

27. Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection

Author

Agrati, C, primary, Castilletti, C, additional, Casetti, R, additional, Sacchi, A, additional, Falasca, L, additional, Turchi, F, additional, Tumino, N, additional, Bordoni, V, additional, Cimini, E, additional, Viola, D, additional, Lalle, E, additional, Bordi, L, additional, Lanini, S, additional, Martini, F, additional, Nicastri, E, additional, Petrosillo, N, additional, Puro, V, additional, Piacentini, M, additional, Di Caro, A, additional, Kobinger, G P, additional, Zumla, A, additional, Ippolito, G, additional, and Capobianchi, M R, additional

Published
2016
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43. Uremic toxins: A new focus on an old subject

Author

Yavuz, A, Tetta, C, Ersoy, Ff, D'Intini, V, Ratanarat, R, De Cal, M, Bonello, M, Bordoni, V, Salvatori, G, Andrikos, E, Yakupoglu, G, Levin, Nw, and Ronco, C

Published
2005

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