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194 results on '"Sanguinetti M (ORCID:0000-0002-9780-7059)"'

1. Enhancing fluconazole reactivation against Candida auris: efficacy of Cinnamomum zeylanicum essential oil versus cinnamaldehyde

Author: Di Vito, Maura, Rosato, Roberto, Rizzo, Silvia, Cacaci, Margherita, Urbani, Andrea, Sanguinetti, Maurizio, Bugli, Francesca, Di Vito, M (ORCID:0000-0002-2991-0855), Rosato, R, Rizzo, S, Cacaci, M (ORCID:0000-0002-5433-9400), Urbani, A (ORCID:0000-0001-9168-3174), Sanguinetti, M (ORCID:0000-0002-9780-7059), Bugli, F (ORCID:0000-0001-9038-3233), Di Vito, Maura, Rosato, Roberto, Rizzo, Silvia, Cacaci, Margherita, Urbani, Andrea, Sanguinetti, Maurizio, Bugli, Francesca, Di Vito, M (ORCID:0000-0002-2991-0855), Rosato, R, Rizzo, S, Cacaci, M (ORCID:0000-0002-5433-9400), Urbani, A (ORCID:0000-0001-9168-3174), Sanguinetti, M (ORCID:0000-0002-9780-7059), and Bugli, F (ORCID:0000-0001-9038-3233)
Abstract: n/a
Published: 2024

2. Slow and steady wins the race: Fractionated near-infrared treatment empowered by graphene-enhanced 3D scaffolds for precision oncology

Author: Perini, Giordano, Palmieri, V., Papait, Andrea, Augello, A., Fioretti, D., Iurescia, S., Rinaldi, M., Vertua, E., Silini, Antonietta Rosa, Torelli, R., Carlino, Anastasia, Musarra, T., Sanguinetti, Maurizio, Parolini, Ornella, De Spirito, Marco, Papi, Massimiliano, Perini G. (ORCID:0000-0001-9452-8479), Papait A. (ORCID:0000-0003-1229-9671), Silini A., Carlino A., Sanguinetti M. (ORCID:0000-0002-9780-7059), Parolini O. (ORCID:0000-0002-5211-6430), De Spirito M. (ORCID:0000-0003-4260-5107), Papi M. (ORCID:0000-0002-0029-1309), Perini, Giordano, Palmieri, V., Papait, Andrea, Augello, A., Fioretti, D., Iurescia, S., Rinaldi, M., Vertua, E., Silini, Antonietta Rosa, Torelli, R., Carlino, Anastasia, Musarra, T., Sanguinetti, Maurizio, Parolini, Ornella, De Spirito, Marco, Papi, Massimiliano, Perini G. (ORCID:0000-0001-9452-8479), Papait A. (ORCID:0000-0003-1229-9671), Silini A., Carlino A., Sanguinetti M. (ORCID:0000-0002-9780-7059), Parolini O. (ORCID:0000-0002-5211-6430), De Spirito M. (ORCID:0000-0003-4260-5107), and Papi M. (ORCID:0000-0002-0029-1309)
Abstract: Surgically addressing tumors poses a challenge, requiring a tailored, multidisciplinary approach for each patient based on the unique aspects of their case. Innovative therapeutic regimens combined to reliable reconstructive methods can contribute to an extended patient's life expectancy. This study presents a detailed comparative investigation of near-infrared therapy protocols, examining the impact of non-fractionated and fractionated irradiation regimens on cancer treatment. The therapy is based on the implantation of graphene oxide/poly(lactic-co-glycolic acid) three-dimensional printed scaffolds, exploring their versatile applications in oncology by the examination of pro-inflammatory cytokine secretion, immune response, and in vitro and in vivo tumor therapy. The investigation into cell death patterns (apoptosis vs necrosis) underlines the pivotal role of protocol selection underscores the critical influence of treatment duration on cell fate, establishing a crucial parameter in therapeutic decision-making. In vivo experiments corroborated the profound impact of protocol selection on tumor response. The fractionated regimen emerged as the standout performer, achieving a substantial reduction in tumor size over time, surpassing the efficacy of the non-fractionated approach. Additionally, the fractionated regimen exhibited efficacy also in targeting tumors in proximity but not in direct contact to the scaffolds. Our results address a critical gap in current research, highlighting the absence of a standardized protocol for optimizing the outcome of photodynamic therapy. The findings underscore the importance of personalized treatment strategies in achieving optimal therapeutic efficacy for precision cancer therapy.
Published: 2024

3. Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis

Author: Fragkou, P. C., Moschopoulos, C. D., Dimopoulou, D., Ong, D. S. Y., Dimopoulou, K., Nelson, P. P., Schweitzer, V. A., Janocha, H., Karofylakis, E., Papathanasiou, K. A., Tsiordras, S., De Angelis, Giulia, Tholken, C., Sanguinetti, Maurizio, Chung, H. -R., Skevaki, C., De Angelis G. (ORCID:0000-0002-7087-7399), Sanguinetti M. (ORCID:0000-0002-9780-7059), Fragkou, P. C., Moschopoulos, C. D., Dimopoulou, D., Ong, D. S. Y., Dimopoulou, K., Nelson, P. P., Schweitzer, V. A., Janocha, H., Karofylakis, E., Papathanasiou, K. A., Tsiordras, S., De Angelis, Giulia, Tholken, C., Sanguinetti, Maurizio, Chung, H. -R., Skevaki, C., De Angelis G. (ORCID:0000-0002-7087-7399), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Background: Molecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies. Objectives: The evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings. Data sources: MEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern. Study eligibility criteria: Peer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union. Participants: Close contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age. Test/s: Molecular and/or antigen-based SARS-CoV-2 POCTs. Reference standard: Laboratory-based SARS-CoV-2 RT-PCR. Assessment of risk of bias: Eligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Methods of data synthesis: Summary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome. Results: A total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9–95.4%) and 97.6% (95% CI, 96.6–98.3%), respectively. The sensitivity of antigen-based P
Published: 2023

4. EPI-Net One Health reporting guideline for antimicrobial consumption and resistance surveillance data: a Delphi approach

Author: Babu Rajendran, N., Arieti, F., Mena-Benitez, C. A., Galia, L., Tebon, M., Alvarez, J., Gladstone, B. P., Collineau, L., De Angelis, Giulia, Duro, R., Gaze, W., Gopel, S., Kanj, S. S., Kasbohrer, A., Limmathurotsakul, D., Lopez de Abechuco, E., Mazzolini, E., Mutters, N. T., Pezzani, M. D., Presterl, E., Renk, H., Rodriguez-Bano, J., Sandulescu, O., Scali, F., Skov, R., Velavan, T. P., Vuong, C., Tacconelli, Evelina, Adegnika, A. A., Avery, L., Bonten, M., Cassini, A., Chauvin, C., Compri, M., Damborg, P., De Greeff, S., Del Toro, M. D., Filter, M., Franklin, A., Gonzalez-Zorn, B., Grave, K., Hocquet, D., Hoelzle, L. E., Kalanxhi, E., Laxminarayan, R., Leibovici, L., Malhotra-Kumar, S., Mendelson, M., Paul, M., Munoz Madero, C., Murri, Rita, Piddock, L. J. V., Ruesen, C., Sanguinetti, Maurizio, Schilling, T., Schrijver, R., Schwaber, M. J., Scudeller, L., Torumkuney, D., Van Boeckel, T., Vanderhaeghen, W., Voss, A., Wozniak, T., De Angelis G. (ORCID:0000-0002-7087-7399), Tacconelli E. (ORCID:0000-0001-8722-5824), Murri R. (ORCID:0000-0003-4263-7854), Sanguinetti M. (ORCID:0000-0002-9780-7059), Babu Rajendran, N., Arieti, F., Mena-Benitez, C. A., Galia, L., Tebon, M., Alvarez, J., Gladstone, B. P., Collineau, L., De Angelis, Giulia, Duro, R., Gaze, W., Gopel, S., Kanj, S. S., Kasbohrer, A., Limmathurotsakul, D., Lopez de Abechuco, E., Mazzolini, E., Mutters, N. T., Pezzani, M. D., Presterl, E., Renk, H., Rodriguez-Bano, J., Sandulescu, O., Scali, F., Skov, R., Velavan, T. P., Vuong, C., Tacconelli, Evelina, Adegnika, A. A., Avery, L., Bonten, M., Cassini, A., Chauvin, C., Compri, M., Damborg, P., De Greeff, S., Del Toro, M. D., Filter, M., Franklin, A., Gonzalez-Zorn, B., Grave, K., Hocquet, D., Hoelzle, L. E., Kalanxhi, E., Laxminarayan, R., Leibovici, L., Malhotra-Kumar, S., Mendelson, M., Paul, M., Munoz Madero, C., Murri, Rita, Piddock, L. J. V., Ruesen, C., Sanguinetti, Maurizio, Schilling, T., Schrijver, R., Schwaber, M. J., Scudeller, L., Torumkuney, D., Van Boeckel, T., Vanderhaeghen, W., Voss, A., Wozniak, T., De Angelis G. (ORCID:0000-0002-7087-7399), Tacconelli E. (ORCID:0000-0001-8722-5824), Murri R. (ORCID:0000-0003-4263-7854), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries—52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach.
Published: 2023

5. Graphene–Curcumin Coatings Resistant to SARS-CoV-2 and Mycobacteria for the Production of Personal Protective Equipment

Author: De Maio, Flavio, Santarelli, Giulia, Palmieri, V., Perini, Giordano, Salustri, Alessandro, Palucci, Ivana, Delli Carpini, Giovanni, Augello, A., Sanguinetti, Maurizio, De Spirito, Marco, Sali, M., Delogu, Giovanni, Papi, Massimiliano, De Maio F., Santarelli G., Perini G. (ORCID:0000-0001-9452-8479), Salustri A., Palucci I., Delli Carpini G., Sanguinetti M. (ORCID:0000-0002-9780-7059), De Spirito M. (ORCID:0000-0003-4260-5107), Delogu G. (ORCID:0000-0003-0182-8267), Papi M. (ORCID:0000-0002-0029-1309), De Maio, Flavio, Santarelli, Giulia, Palmieri, V., Perini, Giordano, Salustri, Alessandro, Palucci, Ivana, Delli Carpini, Giovanni, Augello, A., Sanguinetti, Maurizio, De Spirito, Marco, Sali, M., Delogu, Giovanni, Papi, Massimiliano, De Maio F., Santarelli G., Perini G. (ORCID:0000-0001-9452-8479), Salustri A., Palucci I., Delli Carpini G., Sanguinetti M. (ORCID:0000-0002-9780-7059), De Spirito M. (ORCID:0000-0003-4260-5107), Delogu G. (ORCID:0000-0003-0182-8267), and Papi M. (ORCID:0000-0002-0029-1309)
Abstract: Respiratory tract infections represent the main cause of death from infectious diseases worldwide. SARS-CoV-2 infection (i.e. COVID-19) added to the existing global burden of respiratory tract infections, including tuberculosis. Among nanomaterials for fabric functionalization, graphene, in combination with hydrophobic molecules such as phytochemicals, represents a promising low-cost alternative to antibiotics. In this work, we used graphene and curcumin to create fabric coatings on cotton and polyester for the production of personal protective equipment resistant to infective agents. These coatings ensure the trapping of microorganisms via interaction with SARS-CoV-2 or mycobacteria surface and inhibit microbial infections.
Published: 2023

6. “CORE” a new assay for rapid identification of Klebsiella pneumoniae COlistin REsistant strains by MALDI-TOF MS in positive-ion mode

Author: Foglietta, G., De Carolis, Elena, Mattana, G., Onori, M., Agosta, M., Niccolai, C., Di Pilato, V., Rossolini, G. M., Sanguinetti, Maurizio, Perno, C. F., Bernaschi, P., De Carolis E. (ORCID:0000-0003-4757-7256), Sanguinetti M. (ORCID:0000-0002-9780-7059), Foglietta, G., De Carolis, Elena, Mattana, G., Onori, M., Agosta, M., Niccolai, C., Di Pilato, V., Rossolini, G. M., Sanguinetti, Maurizio, Perno, C. F., Bernaschi, P., De Carolis E. (ORCID:0000-0003-4757-7256), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Due to the global spread of pan resistant organisms, colistin is actually considered as one of the last resort antibiotics against MDR and XDR bacterial infections. The emergence of colistin resistant strains has been observed worldwide in Gram-negative bacteria, such as Enterobacteriaceae and especially in K. pneumoniae, in association with increased morbidity and mortality. This landscape implies the exploration of novel assays able to target colistin resistant strains rapidly. In this study, we developed and evaluated a new MALDI-TOF MS assay in positive-ion mode that allows quantitative or qualitative discrimination between colistin susceptible (18) or resistant (32) K. pneumoniae strains in 3 h by using the “Autof MS 1000” mass spectrometer. The proposed assay, if integrated in the diagnostic workflow, may be of help for the antimicrobial stewardship and the control of the spread of K. pneumoniae colistin resistant isolates in hospital settings.
Published: 2023

7. Curcumin-Functionalized Graphene Oxide Strongly Prevents Candida parapsilosis Adhesion and Biofilm Formation

Author: Cacaci, Margherita, Squitieri, Damiano, Palmieri, Valentina, Torelli, Riccardo, Perini, Giordano, Campolo, M, Di Vito, Maura, Papi, Massimiliano, Posteraro, Brunella, Sanguinetti, Maurizio, Bugli, Francesca, Cacaci, M (ORCID:0000-0002-5433-9400), Squitieri, D, Palmieri, V, Torelli, R, Perini, G (ORCID:0000-0001-9452-8479), Di Vito, M (ORCID:0000-0002-2991-0855), Papi, M (ORCID:0000-0002-0029-1309), Posteraro, B (ORCID:0000-0002-1663-7546), Sanguinetti, M (ORCID:0000-0002-9780-7059), Bugli, F (ORCID:0000-0001-9038-3233), Cacaci, Margherita, Squitieri, Damiano, Palmieri, Valentina, Torelli, Riccardo, Perini, Giordano, Campolo, M, Di Vito, Maura, Papi, Massimiliano, Posteraro, Brunella, Sanguinetti, Maurizio, Bugli, Francesca, Cacaci, M (ORCID:0000-0002-5433-9400), Squitieri, D, Palmieri, V, Torelli, R, Perini, G (ORCID:0000-0001-9452-8479), Di Vito, M (ORCID:0000-0002-2991-0855), Papi, M (ORCID:0000-0002-0029-1309), Posteraro, B (ORCID:0000-0002-1663-7546), Sanguinetti, M (ORCID:0000-0002-9780-7059), and Bugli, F (ORCID:0000-0001-9038-3233)
Abstract: Candida parapsilosis is the major non-C. albicans species involved in the colonization of central venous catheters, causing bloodstream infections. Biofilm formation on medical devices is considered one of the main causes of healthcare-associated infections and represents a global public health problem. In this context, the development of new nanomaterials that exhibit anti-adhesive and anti-biofilm properties for the coating of medical devices is crucial. In this work, we aimed to characterize the antimicrobial activity of two different coated-surfaces, graphene oxide (GO) and curcumin-graphene oxide (GO/CU) for the first time, against C. parapsilosis. We report the capacity of GO to bind and stabilize CU molecules, realizing a homogenous coated surface. We tested the anti-planktonic activity of GO and GO/CU by growth curve analysis and quantification of Reactive Oxigen Species( ROS) production. Then, we tested the antibiofilm activity by adhesion assay, crystal violet assay, and live and dead assay; moreover, the inhibition of the formation of a mature biofilm was investigated by a viability test and the use of specific dyes for the visualization of the cells and the extra-polymeric substances. Our data report that GO/CU has anti-planktonic, anti-adhesive, and anti-biofilm properties, showing a 72% cell viability reduction and a decrease of 85% in the secretion of extra-cellular substances (EPS) after 72 h of incubation. In conclusion, we show that the GO/CU conjugate is a promising material for the development of medical devices that are refractory to microbial colonization, thus leading to a decrease in the impact of biofilm-related infections.
Published: 2023

8. Identification of early predictors of clinical outcomes of COVID-19 outbreak in an Italian single center using a machine-learning approach

Author: Rando, Maria Margherita, Biscetti, Federico, Masciocchi, Carlotta, Capocchiano, Nikola Dino, Nicolazzi, Maria Anna, Nardella, Elisabetta, Cecchini, Andrea Leonardo, Pecorini, Giovanni, Colosimo, C, Sanguinetti, Maurizio, Massetti, Massimo, Gasbarrini, Antonio, Flex, Andrea, Rando, M M, Biscetti, F (ORCID:0000-0001-7449-657X), Masciocchi, C, Capocchiano, N D, Nicolazzi, M A, Nardella, E, Cecchini, A L, Pecorini, G (ORCID:0000-0002-0729-6719), Sanguinetti, M (ORCID:0000-0002-9780-7059), Massetti, M (ORCID:0000-0002-7100-8478), Gasbarrini, A (ORCID:0000-0002-7278-4823), Flex, A (ORCID:0000-0003-2664-4165), Rando, Maria Margherita, Biscetti, Federico, Masciocchi, Carlotta, Capocchiano, Nikola Dino, Nicolazzi, Maria Anna, Nardella, Elisabetta, Cecchini, Andrea Leonardo, Pecorini, Giovanni, Colosimo, C, Sanguinetti, Maurizio, Massetti, Massimo, Gasbarrini, Antonio, Flex, Andrea, Rando, M M, Biscetti, F (ORCID:0000-0001-7449-657X), Masciocchi, C, Capocchiano, N D, Nicolazzi, M A, Nardella, E, Cecchini, A L, Pecorini, G (ORCID:0000-0002-0729-6719), Sanguinetti, M (ORCID:0000-0002-9780-7059), Massetti, M (ORCID:0000-0002-7100-8478), Gasbarrini, A (ORCID:0000-0002-7278-4823), and Flex, A (ORCID:0000-0003-2664-4165)
Abstract: OBJECTIVE: SARS-CoV-2 disease (COVID-19) has become a pandemic disease, determining a public health emergency. The use of artificial intelligence in identifying easily available biomarkers capable of predicting the risk for severe disease may be helpful in guiding clinical decisions. The aim of the study was to investigate the ability of interleukin (IL)-6, troponin I, and D-dimer to identify patients with COVID-19 at risk for intensive care unit (ICU)-admission and death by using a machine-learning predictive model. PATIENTS AND METHODS: Data on demographic characteristics, underlying comorbidities, symptoms, physical and radiological findings, and laboratory tests have been retrospectively collected from electronic medical records of patients admitted to Policlinico A. Gemelli Foundation from March 1, 2020, to September 15, 2020, by using artificial intelligence techniques. RESULTS: From an initial cohort of 425 patients, 146 met the inclusion criteria and were enrolled in the study. The in-hospital mortality rate was 15%, and the ICU admission rate was 41%. Patients who died had higher troponin I (p-value<0.01) and IL -6 values (p-value=0.04), compared to those who survived. Patients admitted to ICU had higher lev- els of troponin I (p-value<0.01) and IL-6 (p-val- ue<0.01), compared to those not admitted to ICU. Threshold values to predict in-hospital mortality and ICU admission have been identified. IL-6 levels higher than 15.133 ng/L have been associated with a 22.91% risk of in-hospital mortality, and IL-6 levels higher than 25.65 ng/L have been as- sociated with a 56.16% risk of ICU admission. Troponin I levels higher than 12 ng/L have been associated with a 26.76% risk of in-hospital mortality and troponin I levels higher than 12 ng/L have been associated with a 52.11% risk of ICU admission. CONCLUSIONS: Levels of IL-6 and troponin I are associated with poor COVID-19 outcomes. Cut-off values capable of predicting in-hospi- tal mortality and ICU admi
Published: 2023

9. Cinnamaldehyde Loaded Poly(lactide-co-glycolide) (PLGA) Microparticles for Antifungal Delivery Application against Resistant Candida albicans and Candida glabrata

Author: Rizzo, Silvia, Di Vito, Maura, Mazzinelli, Elena, Favuzzi, Ilaria, Torelli, Riccardo, Cacaci, Margherita, Arcovito, Alessandro, Sanguinetti, Maurizio, Garzoli, Stefania, Nocca, Giuseppina, Bugli, Francesca, Rizzo S., Di Vito M. (ORCID:0000-0002-2991-0855), Mazzinelli E., Favuzzi I., Torelli R., Cacaci M. (ORCID:0000-0002-5433-9400), Arcovito A. (ORCID:0000-0002-8384-4844), Sanguinetti M. (ORCID:0000-0002-9780-7059), Garzoli S., Nocca G. (ORCID:0000-0002-2799-4557), Bugli F. (ORCID:0000-0001-9038-3233), Rizzo, Silvia, Di Vito, Maura, Mazzinelli, Elena, Favuzzi, Ilaria, Torelli, Riccardo, Cacaci, Margherita, Arcovito, Alessandro, Sanguinetti, Maurizio, Garzoli, Stefania, Nocca, Giuseppina, Bugli, Francesca, Rizzo S., Di Vito M. (ORCID:0000-0002-2991-0855), Mazzinelli E., Favuzzi I., Torelli R., Cacaci M. (ORCID:0000-0002-5433-9400), Arcovito A. (ORCID:0000-0002-8384-4844), Sanguinetti M. (ORCID:0000-0002-9780-7059), Garzoli S., Nocca G. (ORCID:0000-0002-2799-4557), and Bugli F. (ORCID:0000-0001-9038-3233)
Abstract: Researchers have explored natural products to combat the antibiotic resistance of various microorganisms. Cinnamaldehyde (CIN), a major component of cinnamon essential oil (CC-EO), has been found to effectively inhibit the growth of bacteria, fungi, and mildew, as well as their production of toxins. Therefore, this study aimed to create a delivery system for CIN using PLGA microparticles (CIN-MPs), and to compare the antifungal activity of the carried and free CIN, particularly against antibiotic-resistant strains of Candida spp. The first part of the study focused on synthesizing and characterizing the PLGA MPs, which had no toxic effects in vivo and produced results in line with the existing literature. The subsequent experiments analyzed the antifungal effects of MPs-CIN on Candida albicans and Candida glabrata, both resistant (R) and sensitive (S) strains and compared its efficacy with the conventional addition of free CIN to the culture medium. The results indicated that conveyed CIN increased the antifungal effects of the product, particularly towards C. albicans R. The slow and prolonged release of CIN from the PLGA MPs ensured a constant and uniform concentration of the active principle within the cells.
Published: 2023

10. Effect of acute histologic chorioamnionitis on bronchopulmonary dysplasia and mortality rate among extremely low gestational age neonates: A retrospective case–control study

Author: Costa, S., Fattore, Simona, De Santis, Marco, Lanzone, Antonio, Spanu Pennestri, Teresa, Arena, Vincenzo, Tana, Milena, Trapani, Mariarita, Sanguinetti, Maurizio, Barnea, E. R., Vento, Giovanni, Fattore S., De-Santis M. (ORCID:0000-0002-1388-0014), Lanzone A. (ORCID:0000-0003-4119-414X), Spanu T. (ORCID:0000-0003-1864-5184), Arena V. (ORCID:0000-0002-7562-223X), Tana M., Trapani M., Sanguinetti M. (ORCID:0000-0002-9780-7059), Vento G. (ORCID:0000-0002-8132-5127), Costa, S., Fattore, Simona, De Santis, Marco, Lanzone, Antonio, Spanu Pennestri, Teresa, Arena, Vincenzo, Tana, Milena, Trapani, Mariarita, Sanguinetti, Maurizio, Barnea, E. R., Vento, Giovanni, Fattore S., De-Santis M. (ORCID:0000-0002-1388-0014), Lanzone A. (ORCID:0000-0003-4119-414X), Spanu T. (ORCID:0000-0003-1864-5184), Arena V. (ORCID:0000-0002-7562-223X), Tana M., Trapani M., Sanguinetti M. (ORCID:0000-0002-9780-7059), and Vento G. (ORCID:0000-0002-8132-5127)
Abstract: ObjectiveTo evaluate whether acute histologic chorioamnionitis (HCA) diagnosed in the placenta may be associated with an increased occurrence of bronchopulmonary dysplasia (BPD) or death among extremely low gestational age neonates (ELGAN).MethodsThis Italian single-center case-control retrospective study involved ELGAN admitted to the neonatal intensive care unit between January 2019 and June 2022. Infants born from pregnant women with acute and severe HCA, identified as stage >= 2 and grade 2 HCA, (HCA-infants) were compared with infants of pregnant women without chorioamnionitis or with stage 1, grade 1 chorioamnionitis (no-HCA-infants).ResultsAmong 101 eligible ELGAN, 63 infants had complete clinical and histologic data relevant to the study: thirty infants were included in the HCA-infants group and 33 in the no-HCA-infants group. Neonatal and maternal demographic and clinical characteristics were similar between the two groups. Infants born from mothers with acute and severe HCA had significantly higher occurrence of composite BPD or death (18 [60%] vs. 9 [27%]; P = 0.012), as well as higher incidence of severe forms of BPD (6 [30%] vs. 2 [6%]; P = 0.045). In multiple logistic regression analysis, after adjustment for confounding covariates, HCA was an independent risk factor for BPD or death (OR, 4.49; 95% CI: 1.47-13.71).ConclusionsThis is the first study showing that in utero exposure to acute and severe HCA is an independent risk factor for the occurrence of composite BPD or death among ELGAN.Acute and severe histologic chorioamnionitis is an independent risk factor for the occurrence of bronchopulmonary dysplasia or death among extremely low gestational age neonates.
Published: 2023

11. Inactivation of the Response Regulator AgrA Has a Pleiotropic Effect on Biofilm Formation, Pathogenesis and Stress Response in Staphylococcus lugdunensis

Author: Aubourg, M., Pottier, M., Leon, A., Bernay, B., Dhalluin, A., Cacaci, M., Torelli, R. (ORCID:0000-0003-1956-3981), Ledormand, P., Martini, C., Sanguinetti, M. (ORCID:0000-0002-9780-7059), Auzou, M., Gravey, F., Giard, J. -C., Aubourg, M., Pottier, M., Leon, A., Bernay, B., Dhalluin, A., Cacaci, M., Torelli, R. (ORCID:0000-0003-1956-3981), Ledormand, P., Martini, C., Sanguinetti, M. (ORCID:0000-0002-9780-7059), Auzou, M., Gravey, F., and Giard, J. -C.
Abstract: Staphylococcus lugdunensis is a coagulase-negative Staphylococcus that emerges as an important opportunistic pathogen. However, little is known about the regulation underlying the transition from commensal to virulent state. Based on knowledge of S. aureus virulence, we suspected that the agr quorum sensing system may be an important determinant for the pathogenicity of S. lugdunensis. We investigated the functions of the transcriptional regulator AgrA using the agrA deletion mutant. AgrA played a role in cell pigmentation: DargA mutant colonies were white while the parental strains were slightly yellow. Compared with the wild-type strain, the DargA mutant was affected in its ability to form biofilm and was less able to survive in mice macrophages. Moreover, the growth of DagrA was significantly reduced by the addition of 10% NaCl or 0.4 mM H2O2 and its survival after 2 h in the presence of 1 mM H2O2 was more than 10-fold reduced. To explore the mechanisms involved beyond these phenotypes, the DagrA proteome and transcriptome were characterized by mass spectrometry and RNA-Seq. We found that AgrA controlled several virulence factors as well as stress-response factors, which are well correlated with the reduced resistance of the DagrA mutant to osmotic and oxidative stresses. These results were not the consequence of the deregulation of RNAIII of the agr system, since no phenotype or alteration of the proteomic profile has been observed for the DRNAIII mutant. Altogether, our results highlighted that the AgrA regulator of S. lugdunensis played a key role in its ability to become pathogenic.
Published: 2022

12. VERTICAL TRANSMISSION OF SARS-COV-2 DURING PREGNANCY : A PROSPECTIVE ITALIAN COHORT STUDY

Author: Costa, S, Giordano, Lucia, Bottoni, Rossella Alessandra, Tiberi, Eloisa, Fattore, Simona, Pastorino, Roberta, Di Simone, Nicoletta, Lanzone, Antonio, Buonsenso, Danilo, Valentini, Piero, Cattani, P, Santangelo, Rosaria, Sanguinetti, Maurizio, Scambia, Giovanni, Vento, Giovanni, COSTA S, GIORDANO L, BOTTONI A (ORCID:0000-0002-0155-2195), TIBERI E, FATTORE S, PASTORINO R (ORCID:0000-0001-5013-0733), DI SIMONE N (ORCID:0000-0003-1273-3335), LANZONE A (ORCID:0000-0003-4119-414X), BUONSENSO D, VALENTINI P (ORCID:0000-0001-6095-9510), CATTANI P, SANTANGELO R (ORCID:0000-0002-8056-218X), SANGUINETTI M (ORCID:0000-0002-9780-7059), SCAMBIA G (ORCID:0000-0003-2758-1063), VENTO G. (ORCID:0000-0002-8132-5127), Costa, S, Giordano, Lucia, Bottoni, Rossella Alessandra, Tiberi, Eloisa, Fattore, Simona, Pastorino, Roberta, Di Simone, Nicoletta, Lanzone, Antonio, Buonsenso, Danilo, Valentini, Piero, Cattani, P, Santangelo, Rosaria, Sanguinetti, Maurizio, Scambia, Giovanni, Vento, Giovanni, COSTA S, GIORDANO L, BOTTONI A (ORCID:0000-0002-0155-2195), TIBERI E, FATTORE S, PASTORINO R (ORCID:0000-0001-5013-0733), DI SIMONE N (ORCID:0000-0003-1273-3335), LANZONE A (ORCID:0000-0003-4119-414X), BUONSENSO D, VALENTINI P (ORCID:0000-0001-6095-9510), CATTANI P, SANTANGELO R (ORCID:0000-0002-8056-218X), SANGUINETTI M (ORCID:0000-0002-9780-7059), SCAMBIA G (ORCID:0000-0003-2758-1063), and VENTO G. (ORCID:0000-0002-8132-5127)
Abstract: OBJECTIVE: THE EXTENT OF VERTICAL TRANSMISSION ( VT ) OF SARS-COV-2 FROM MOTHERS TO NEONATES IS STILL UNCERTAIN. WE AIMED TO DETERMINE THE INCIDENCE OF VT. STUDY DESIGN: IN THIS PROSPECTIVE COHORT STUDY ALL MOTHER DIAGNOSED WITH SARS-COV-2 INFECTION AT TIME OF DELIVERY OR UP TO ONE WEEK PRIOR AND THEIR NEONATE MANAGED IN A TERTIARY REFERRAL HOSPITAL FOR PREGNANCY COMPLICATED BY COVID-19 IN ROME, FROM APRIL 2 TO DECEMBER 22,2020,WERE INCLUDED.MATERNAL INFECTION WAS DEFINED AS NASOPHARYNGEAL SWAB TEST RESULTS POSITIVE FOR SARS-COV-2 RT-PCR. BIOLOGICAL SAMPLES WERE COLLECTED BEFORE, AT, AND AFTER DELIVERY TO TEST POSITIVITY FOR SARS-COV-2 RT-PCR AND ANTI SARS-COV-2 SPECIFIC ANTIBODIES. RESULTS: THE COHORT INCLUDED 95 WOMEN AND 96 NEONATES WITH DOCUMENTED SARS-COV-2 TEST RESULTS. FOUR NEONATES ( 4.2% ) TESTED POSITIVE. THE INCIDENCE OF VT, ACCORDING TO THE GUIDANCE CRITERIA FOR DIAGNOSING PERNATAL SARS-COV-2 INFECTION,WAS 5.2%. NEONATAL SYMPTOMS WERE DUE TO PREMATURITY OR FETAL DISTRESS: SYMPTOMATIC INFANTS HAD LOWER MEDIAN [ MIN-MAX ] GESTATIONAL AGE ( 38.1 [29.3-40.6] VS 39.3 [33.9-41.9] WEEKS ; P= .036), 1-MIN ( 9[3-9]VS 9[7-10]; P= .036), AND 5-MIN APGAR SCORES (10[6-10] VS 10[8-10]; P= .012) THAN ASYMPTOMATIC INFANTS, AND NEEDED MORE FREQUENTLY ASSISTANCE IN THE DELIVERY ROOM ( 22.2% VS 2.5%; P= .0089. ONLY 6(7.1%) NEONATES HAD ANTI SARS-COV-2 SPECIFIC ANTIBODIES,DESPITE THE ONGOING MATERNAL INFECTION. CONCLUSIONS: THE INCIDENCE OF VT IS LOW AS IS THE DETECTION OF SPECIFIC ANTI SARS-COV-2 ANTIBODIES IN CORD BLOOD WHEN INFECTION IS CONTRACTED LATE IN PREGNANCY.THIS WOULD SUGGEST POOR PROTECTION OF INFANTS AGAINST HORIZONTAL TRANSMISSION OF THE VIRUS
Published: 2022

13. Gut Dysbiosis and Fecal Calprotectin Predict Response to Immune Checkpoint Inhibitors in Patients With Hepatocellular Carcinoma

Author: Ponziani, Francesca Romana, De Luca, A., Picca, A., Marzetti, Emanuele, Petito, Valentina, Del Chierico, F., Reddel, S., Paroni Sterbini, F., Sanguinetti, Maurizio, Putignani, Lorenza, Gasbarrini, Antonio, Pompili, Maurizio, Ponziani F. R. (ORCID:0000-0002-5924-6238), Marzetti E. (ORCID:0000-0001-9567-6983), Petito V., Sanguinetti M. (ORCID:0000-0002-9780-7059), Putignani L., Gasbarrini A. (ORCID:0000-0002-7278-4823), Pompili M. (ORCID:0000-0001-6699-7980), Ponziani, Francesca Romana, De Luca, A., Picca, A., Marzetti, Emanuele, Petito, Valentina, Del Chierico, F., Reddel, S., Paroni Sterbini, F., Sanguinetti, Maurizio, Putignani, Lorenza, Gasbarrini, Antonio, Pompili, Maurizio, Ponziani F. R. (ORCID:0000-0002-5924-6238), Marzetti E. (ORCID:0000-0001-9567-6983), Petito V., Sanguinetti M. (ORCID:0000-0002-9780-7059), Putignani L., Gasbarrini A. (ORCID:0000-0002-7278-4823), and Pompili M. (ORCID:0000-0001-6699-7980)
Abstract: The gut microbiota is a well-known prognostic factor and a modulator of treatment sensitivity in patients with cancers treated with immune checkpoint inhibitors. However, data on hepatocellular carcinoma (HCC) are lacking. This study aimed to evaluate the prognostic role of the gut microbiota and changes produced by immunotherapy on the intestinal environment in patients with cirrhosis and HCC. Eleven patients treated with Tremelimumab and/or Durvalumab were included in the analysis. All study participants underwent gut microbiota profiling, quantification of fecal calprotectin, serum levels of zonulin-1, lipopolysaccharide binding protein (LBP), and programmed death-ligand 1 (PD-L1) at baseline and at each treatment cycle until the third cycle, then every three cycles until treatment discontinuation or last visit. The 6 patients who achieved disease control (DC) showed lower pretreatment fecal calprotectin (median, 12.5; interquartile range [IQR], 5-29 vs. median, 116; IQR, 59-129 µg/g; P = 0.047) and PD-L1 serum levels (median, 0.08; IQR, 0.07-0.09 vs. median, 1.04; IQR, 0.17-1.95 ng/mL; P = 0.02) than nonresponders. The relative abundance of Akkermansia (log2 fold change [FC], 2.72; adjusted P [Padj] = 0.012) was increased, whereas that of Enterobacteriaceae (log2 FC, −2.34; Padj = 0.04) was reduced in the DC group. During treatment, fecal calprotectin showed a temporal evolution opposite to the Akkermansia to Enterobacteriaceae ratio and gut microbiota alpha diversity, but similar to zonulin-1 and LBP. Bifidobacterium had a stable behavior in patients with a long follow-up, while Akkermansia was more variable. Akkermansia and Bifidobacterium showed similar temporal patterns and causative relationships with Prevotella, Veillonella, Ruminococcus, Roseburia, Lachnospira, Faecalibacterium, and Clostridium. Conclusion: A favorable composition of the gut microbiota and low intestinal inflammation are associated with ac
Published: 2022

14. Multiplex PCR Detection of Respiratory Tract Infections in SARS-CoV-2-Negative Patients Admitted to the Emergency Department: an International Multicenter Study during the COVID-19 Pandemic

Author: Duclos, M., Hommel, B., Allantaz, F., Powell, M., Posteraro, Brunella, Sanguinetti, Maurizio, Habous, M., Dabal, L., Kilercik, M., Uyar, N. Y., Bozdayi, G., Caglar, K., Otlu, B., Yakupogullari, Y., Karalti, I., Tagiyev, B., Almaghrabi, R. S., Althawadi, S., Qasem, M. G., Alzahrani, A., Streinu-Cercel, A., Schvoerer, E., Hartard, C., Thibault, V., Pronier, C., Henquell, C., Brebion, A., Pillet, S., Labetoulle, R., Silke, P., Ganzenmueller, T., Schmauder, K., Munoz, P., Albizua, A. B., Kabera, B., Maranga, J., Wolter, N., Du Plessis, M., Famoroti, T., Wadula, J., Nunes, M. C., Rashed, H. G., Elkholy, M. M., Yahia, M. B., Elfattah, N. A., Ferjani, A., Boutiba-Ben, I., Hamammi, A., Hakim, H. K., Gdoura, M., Henda, T., Posteraro B. (ORCID:0000-0002-1663-7546), Sanguinetti M. (ORCID:0000-0002-9780-7059), Duclos, M., Hommel, B., Allantaz, F., Powell, M., Posteraro, Brunella, Sanguinetti, Maurizio, Habous, M., Dabal, L., Kilercik, M., Uyar, N. Y., Bozdayi, G., Caglar, K., Otlu, B., Yakupogullari, Y., Karalti, I., Tagiyev, B., Almaghrabi, R. S., Althawadi, S., Qasem, M. G., Alzahrani, A., Streinu-Cercel, A., Schvoerer, E., Hartard, C., Thibault, V., Pronier, C., Henquell, C., Brebion, A., Pillet, S., Labetoulle, R., Silke, P., Ganzenmueller, T., Schmauder, K., Munoz, P., Albizua, A. B., Kabera, B., Maranga, J., Wolter, N., Du Plessis, M., Famoroti, T., Wadula, J., Nunes, M. C., Rashed, H. G., Elkholy, M. M., Yahia, M. B., Elfattah, N. A., Ferjani, A., Boutiba-Ben, I., Hamammi, A., Hakim, H. K., Gdoura, M., Henda, T., Posteraro B. (ORCID:0000-0002-1663-7546), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Respiratory tract infection (RTI) is a common cause of visits to the hospital emergency department. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nonpharmaceutical intervention has influenced the rates of circulating respiratory viruses. In this study, we sought to detect RTI etiological agents other than SARS-CoV-2 in emergency department patients from 13 countries in Europe, the Middle East, and Africa from December 2020 to March 2021. We sought to measure the impact of patient characteristics and national-level behavioral restrictions on the positivity rate for RTI agents. Using the BioFire Respiratory Panel 2.0 Plus, 1,334 nasopharyngeal swabs from patients with RTI symptoms who were negative for SARS-CoV-2 were tested. The rate of positivity for viral or bacterial targets was 36.3%. Regarding viral targets, human rhinovirus or enterovirus was the most prevalent (56.5%), followed by human coronaviruses (11.0%) and adenoviruses (9.9%). Interestingly, age stratification showed that the positivity rate was significantly higher in the children's group than in the adults' group (68.8% versus 28.2%). In particular, human rhinovirus or enterovirus, the respiratory syncytial virus, and other viruses, such as the human metapneumovirus, were more frequently detected in children than in adults. A logistic regression model was also used to determine an association between the rate of positivity for viral agents with each country's behavioral restrictions or with patients' age and sex. Despite the impact of behavioral restrictions, various RTI pathogens were actively circulating, particularly in children, across the 13 countries.
Published: 2022

15. Performance of existing definitions and tests for the diagnosis of invasive aspergillosis in critically ill, non-neutropenic, adult patients: An update including COVID-19 data

Author: Bassetti, M., Zuccaro, V., Asperges, E., Scudeller, L., Giacobbe, D. R., Akova, M., Alastruey-Izquierdo, A., Arikan-Akdagli, S., Azoulay, E., Blot, S., Cortegiani, A., Cornely, O. A., Grecchi, C., Lass-Florl, C., Koehler, P., Cuenca-Estrella, M., de Lange, D. W., De Rosa, F. G., De Waele, J. J., Dimopoulos, G., Garnacho-Montero, J., Hoenigl, M., Kanj, S. S., Lamoth, F., Maertens, J., Martin-Loeches, I., Munoz, P., Kullberg, B. J., Agvald-Ohman, C., Poulakou, G., Rebuffi, C., Rello, J., Sanguinetti, Maurizio, Taccone, F. S., Timsit, J. -F., Torres, A., Vazquez, J. A., Wauters, J., Calandra, T., Tejada, S., Karaiskos, I., Peghin, M., Vena, A., Mortensen, K. L., Lebihan, C., Mercier, T., Sanguinetti M. (ORCID:0000-0002-9780-7059), Bassetti, M., Zuccaro, V., Asperges, E., Scudeller, L., Giacobbe, D. R., Akova, M., Alastruey-Izquierdo, A., Arikan-Akdagli, S., Azoulay, E., Blot, S., Cortegiani, A., Cornely, O. A., Grecchi, C., Lass-Florl, C., Koehler, P., Cuenca-Estrella, M., de Lange, D. W., De Rosa, F. G., De Waele, J. J., Dimopoulos, G., Garnacho-Montero, J., Hoenigl, M., Kanj, S. S., Lamoth, F., Maertens, J., Martin-Loeches, I., Munoz, P., Kullberg, B. J., Agvald-Ohman, C., Poulakou, G., Rebuffi, C., Rello, J., Sanguinetti, Maurizio, Taccone, F. S., Timsit, J. -F., Torres, A., Vazquez, J. A., Wauters, J., Calandra, T., Tejada, S., Karaiskos, I., Peghin, M., Vena, A., Mortensen, K. L., Lebihan, C., Mercier, T., and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Not available
Published: 2022

16. Diagnosis and management of infections caused by multidrug-resistant bacteria: guideline endorsed by the Italian Society of Infection and Tropical Diseases (SIMIT), the Italian Society of Anti-Infective Therapy (SITA), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Association of Clinical Microbiologists (AMCLI) and the Italian Society of Microbiology (SIM)

Author: Tiseo, G., Brigante, G., Giacobbe, D. R., Maraolo, A. E., Gona, F., Falcone, Marco, Giannella, M., Grossi, Paolo, Pea, Federico, Rossolini, G. M., Sanguinetti, Maurizio, Sarti, Daniela Maria, Scarparo, C., Tumbarello, Mario, Venditti, Mario, Viale, P., Bassetti, M., Luzzaro, F., Menichetti, F., Stefani, S., Tinelli, M., Falcone M., Grossi P., Pea F., Sanguinetti M. (ORCID:0000-0002-9780-7059), Sarti M., Tumbarello M. (ORCID:0000-0002-9519-8552), Venditti M., Tiseo, G., Brigante, G., Giacobbe, D. R., Maraolo, A. E., Gona, F., Falcone, Marco, Giannella, M., Grossi, Paolo, Pea, Federico, Rossolini, G. M., Sanguinetti, Maurizio, Sarti, Daniela Maria, Scarparo, C., Tumbarello, Mario, Venditti, Mario, Viale, P., Bassetti, M., Luzzaro, F., Menichetti, F., Stefani, S., Tinelli, M., Falcone M., Grossi P., Pea F., Sanguinetti M. (ORCID:0000-0002-9780-7059), Sarti M., Tumbarello M. (ORCID:0000-0002-9519-8552), and Venditti M.
Abstract: Management of patients with infections caused by multidrug-resistant organisms is challenging and requires a multidisciplinary approach to achieve successful clinical outcomes. The aim of this paper is to provide recommendations for the diagnosis and optimal management of these infections, with a focus on targeted antibiotic therapy. The document was produced by a panel of experts nominated by the five endorsing Italian societies, namely the Italian Association of Clinical Microbiologists (AMCLI), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Society of Microbiology (SIM), the Italian Society of Infectious and Tropical Diseases (SIMIT) and the Italian Society of Anti-Infective Therapy (SITA). Population, Intervention, Comparison and Outcomes (PICO) questions about microbiological diagnosis, pharmacological strategies and targeted antibiotic therapy were addressed for the following pathogens: carbapenem-resistant Enterobacterales; carbapenem-resistant Pseudomonas aeruginosa; carbapenem-resistant Acinetobacter baumannii; and methicillin-resistant Staphylococcus aureus. A systematic review of the literature published from January 2011 to November 2020 was guided by the PICO strategy. As data from randomised controlled trials (RCTs) were expected to be limited, observational studies were also reviewed. The certainty of evidence was classified using the GRADE approach. Recommendations were classified as strong or conditional. Detailed recommendations were formulated for each pathogen. The majority of available RCTs have serious risk of bias, and many observational studies have several limitations, including small sample size, retrospective design and presence of confounders. Thus, some recommendations are based on low or very-low certainty of evidence. Importantly, these recommendations should be continually updated to reflect emerging evidence from clinical studies and real-world experience.
Published: 2022

17. Rapid Detection of the Omicron (B.1.1.529) SARS-CoV-2 Variant Using a COVID-19 Diagnostic PCR Assay

Author: Ippoliti, Chiara, De Maio, Flavio, Santarelli, Giulia, Marchetti, Simona, Vella, Antonietta, Santangelo, Rosaria, Sanguinetti, Maurizio, Posteraro, Brunella, Ippoliti C., De Maio F., Santarelli G., Marchetti S., Vella A., Santangelo R. (ORCID:0000-0002-8056-218X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Posteraro B. (ORCID:0000-0002-1663-7546), Ippoliti, Chiara, De Maio, Flavio, Santarelli, Giulia, Marchetti, Simona, Vella, Antonietta, Santangelo, Rosaria, Sanguinetti, Maurizio, Posteraro, Brunella, Ippoliti C., De Maio F., Santarelli G., Marchetti S., Vella A., Santangelo R. (ORCID:0000-0002-8056-218X), Sanguinetti M. (ORCID:0000-0002-9780-7059), and Posteraro B. (ORCID:0000-0002-1663-7546)
Abstract: The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the last variant of concern (VOC) identified to date. Compared to whole-genome or gene-specific sequencing methods, reverse-transcription PCR assays may be a simpler approach to study VOCs. We used a point-of-care COVID-19 diagnostic PCR assay to detect the Omicron SARS-CoV-2 variant in the respiratory tract samples of COVID-19 patients who had tested positive for SARS-CoV-2 RNA between April 2021 and January 2022. Sequencing analyses had shown that 87 samples were positive for the Omicron variant and 43 samples were positive for a non-Omicron variant (Delta, 18 samples; Alpha, 13 samples; Gamma, 10 samples; Beta, 1 sample; or Epsilon, 1 sample). According to results by the PCR assay, whose primers anneal a nucleocapsid (N) gene region that comprises the E31/R32/S33 deletion (also termed the del31/33 mutation), we found that N gene target failure/dropout (i.e., a negative/low result) occurred in 86 (98.8%) of 87 Omicron variant-positive samples tested. These results were assessed in relation to those of the spike (S) gene, which expectedly, was detected in all (100%) 130 samples. A total of 43 (100%) of 43 Delta, Alpha, Gamma, Beta, or Epsilon variant-positive samples had a positive result with the N gene. Importantly, in 86 of 87 Omicron variant-positive samples, the del31/33 mutation was detected together with a P13L mutation, which was, instead, detected alone in the Omicron variant-positive sample that had a positive N-gene result. IMPORTANCE Rapid detection of the Omicron SARS-CoV-2 variant in patients’ respiratory tract samples may influence therapeutic choices, because this variant is known to escape from certain monoclonal antibodies. Our findings strengthen the importance of manufacturers’ efforts to improve the existing COVID-19 diagnostic PCR assays and/or to develop novel variant-specific PCR assays. Furthermore, our findings show that only a small fraction
Published: 2022

18. Two-Period Study Results from a Large Italian Hospital Laboratory Attesting SARS-CoV-2 Variant PCR Assay Evolution

Author: Liotti, Flora Marzia, De Maio, Flavio, Ippoliti, Chiara, Santarelli, Giulia, Monzo, F. R., Sali, Michela, Santangelo, Rosaria, Ceccherini-Silberstein, F., Sanguinetti, Maurizio, Posteraro, Brunella, Liotti F. M., De Maio F., Ippoliti C., Santarelli G., Sali M. (ORCID:0000-0003-3609-2990), Santangelo R. (ORCID:0000-0002-8056-218X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Posteraro B. (ORCID:0000-0002-1663-7546), Liotti, Flora Marzia, De Maio, Flavio, Ippoliti, Chiara, Santarelli, Giulia, Monzo, F. R., Sali, Michela, Santangelo, Rosaria, Ceccherini-Silberstein, F., Sanguinetti, Maurizio, Posteraro, Brunella, Liotti F. M., De Maio F., Ippoliti C., Santarelli G., Sali M. (ORCID:0000-0003-3609-2990), Santangelo R. (ORCID:0000-0002-8056-218X), Sanguinetti M. (ORCID:0000-0002-9780-7059), and Posteraro B. (ORCID:0000-0002-1663-7546)
Abstract: In keeping with the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 causative agent, PCR assays have been developed to rapidly detect SARS-CoV-2 variants, which have emerged since the first (Alpha) variant was identified. Based on specific assortment of SARS-CoV-2 spike-protein mutations (DH69/V70, E484K, N501Y, W152C, L452R, K417N, and K417T) among the major variants known to date, Seegene Allplex SARS-CoV-2 Variants I and Variants II assays have been available since a few months before the last (Omicron) variant became predominant. Using S gene next-generation sequencing (NGS) as the SARS-CoV-2 variant identification reference method, we assessed the results of SARS-CoV-2-positive nasopharyngeal swab samples from two testing periods, before (n = 288, using only Variants I) and after (n = 77, using both Variants I and Variants II) the appearance of Omicron. The Variants I assay allowed correct identification for Alpha (37/37), Beta/Gamma (28/ 30), or Delta (220/221) variant-positive samples. The combination of the Variants I and Variants II assays allowed correct identification for 61/77 Omicron variant-positive samples. While 16 samples had the K417N mutation undetected with the Variants II assay, 74/77 samples had both DH69/V70 and N501Y mutations detected with the Variants I assay. If considering only the results by the Variants I assay, 6 (2 Beta variant positive, 1 Delta variant positive, and 3 Omicron variant positive) of 365 samples tested in total provided incorrect identification. We showed that the Variants I assay alone might be more suitable than both the Variants I and Variants II assays to identify currently circulating SARS-CoV-2 variants. Inclusion of additional variant-specific mutations should be expected in the development of future assays.
Published: 2022

19. SARS-CoV-2 Antigen Test Results to Infer Active or Non-Active Virus Replication Status in COVID-19 Patients

Author: De Angelis, Giulia, Menchinelli, Giulia, Liotti, Flora Marzia, Marchetti, Simona, Salustri, Alessandro, Vella, Antonietta, Santangelo, Rosaria, Posteraro, Brunella, Sanguinetti, Maurizio, De Angelis G. (ORCID:0000-0002-7087-7399), Menchinelli G., Liotti F. M., Marchetti S., Salustri A., Vella A., Santangelo R. (ORCID:0000-0002-8056-218X), Posteraro B. (ORCID:0000-0002-1663-7546), Sanguinetti M. (ORCID:0000-0002-9780-7059), De Angelis, Giulia, Menchinelli, Giulia, Liotti, Flora Marzia, Marchetti, Simona, Salustri, Alessandro, Vella, Antonietta, Santangelo, Rosaria, Posteraro, Brunella, Sanguinetti, Maurizio, De Angelis G. (ORCID:0000-0002-7087-7399), Menchinelli G., Liotti F. M., Marchetti S., Salustri A., Vella A., Santangelo R. (ORCID:0000-0002-8056-218X), Posteraro B. (ORCID:0000-0002-1663-7546), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: We used nasopharyngeal swab samples of patients with a symptomatic (n = 82) or asymp-tomatic (n = 20) coronavirus disease 2019 (COVID-19) diagnosis to assess the ability of antigen detection tests to infer active (potentially transmissible) or inactive (potentially non-transmissible) infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the subgenomic RNA (sgRNA) as an active replication marker of SARS-CoV-2, 48 (76.2%), 56 (88.9%), and 63 (100%) of 63 samples with sgRNA positive results tested positive with the SD BIOSENSOR STANDARD Q COVID-19 Ag (Standard Q), the SD BIOSENSOR STANDARD F COVID-19 Ag FIA (Standard F), or the Fujirebio LUMIPULSE G SARS-CoV-2 Ag (Lumipulse) assay, respectively. Conversely, 37 (94.9%), 29 (74.4%), and 7 (17.9%) of 39 samples with sgRNA negative results tested negative with Standard Q, Standard F, or Lumipulse, respectively. Stratifying results by the number of days of symptoms before testing revealed that most antigen positive/sgRNA positive results were among samples tested at 2–7 days regardless of the assay used. Conversely, most antigen negative/sgRNA negative results were among samples tested at 16–30 days only when Standard Q or Standard F were used. In conclusion, based on our findings, a negative antigen test, especially with the Lumipulse assay, or a positive antigen test, especially with the Standard F assay, may suggest, respectively, the absence or presence of replication-competent SARS-CoV-2.
Published: 2022

20. Whole-genome sequencing reveals host factors underlying critical COVID-19

Author: Kousathanas, A., Pairo-Castineira, E., Rawlik, K., Stuckey, A., Odhams, C. A., Walker, S., Russell, C. D., Malinauskas, T., Wu, Y., Millar, J., Shen, X., Elliott, K. S., Griffiths, F., Oosthuyzen, W., Morrice, K., Keating, S., Wang, B., Rhodes, D., Klaric, L., Zechner, M., Parkinson, N., Siddiq, A., Goddard, P., Donovan, S., Maslove, D., Nichol, A., Semple, M. G., Zainy, T., Maleady-Crowe, F., Todd, L., Salehi, S., Knight, J., Elgar, G., Chan, G., Arumugam, P., Patch, C., Rendon, A., Bentley, D., Kingsley, C., Kosmicki, J. A., Horowitz, J. E., Baras, A., Abecasis, G. R., Ferreira, M. A. R., Justice, A., Mirshahi, T., Oetjens, M., Rader, D. J., Ritchie, M. D., Verma, A., Fowler, T. A., Shankar-Hari, M., Summers, C., Hinds, C., Horby, P., Mcauley, D., Montgomery, H., Openshaw, P. J. M., Elliott, P., Walsh, T., Tenesa, A., Fawkes, A., Murphy, L., Rowan, K., Ponting, C. P., Vitart, V., Wilson, J. F., Yang, J., Bretherick, A. D., Scott, R. H., Hendry, S. C., Moutsianas, L., Law, A., Caulfield, M. J., Baillie, J. K., Begg, C., Ling, L., Pereira, A. C., Aravindan, L., Armstrong, R., Biggs, H., Boz, C., Brown, A., Clark, R., Coutts, A., Coyle, J., Cullum, L., Das, S., Day, N., Donnelly, L., Duncan, E., Finernan, P., Fourman, M. H., Furlong, A., Furniss, J., Gallagher, B., Gilchrist, T., Golightly, A., Hafezi, K., Hamilton, D., Hendry, R., Law, D., Law, R., Law, S., Lidstone-Scott, R., Macgillivray, L., Maclean, A., Mal, H., Mccafferty, S., Mcmaster, E., Meikle, J., Moore, S. C., Murphy, S., Hellen, M., Zheng, C., Chen, J., Paterson, T., Schon, K., Stenhouse, A., Das, M., Swets, M., Szoor-McElhinney, H., Taneski, F., Turtle, L., Wackett, T., Ward, M., Weaver, J., Wrobel, N., Arbane, G., Bociek, A., Campos, S., Grau, N., Jones, T. O., Lim, R., Marotti, M., Ostermann, M., Whitton, C., Alldis, Z., Astin-Chamberlain, R., Bibi, F., Biddle, J., Blow, S., Bolton, M., Borra, C., Bowles, R., Burton, M., Choudhury, Y., Collier, D., Cox, A., Easthope, A., Ebano, P., Fotiadis, S., Gurasashvili, J., Halls, R., Hartridge, P., Kallon, D., Kassam, J., Lancoma-Malcolm, I., Matharu, M., May, P., Mitchelmore, O., Newman, T., Patel, M., Pheby, J., Pinzuti, I., Prime, Z., Prysyazhna, O., Shiel, J., Taylor, M., Tierney, C., Wood, S., Zak, A., Zongo, O., Bonner, S., Hugill, K., Jones, J., Liggett, S., Headlam, E., Bandla, N., Gellamucho, M., Davies, M., Thompson, C., Abdelrazik, M., Bakthavatsalam, D., Elhassan, M., Ganesan, A., Haldeos, A., Moreno-Cuesta, J., Purohit, D., Vincent, R., Xavier, K., Kumar, R., Frater, Alessia, Saleem, M., Carter, D., Jenkins, S., Lamond, Z., Wall, A., Fernandez-Roman, J., Hamilton, D. O., Johnson, E., Johnston, B., Martinez Guzman, Maria Loreto, Mulla, S., Shaw, D., Waite, A. A. C., Waugh, V., Welters, I. D., Williams, K., Cavazza, A., Cockrell, M., Corcoran, E., Depante, M., Finney, C., Jerome, E., Mcphail, M., Nayak, M., Noble, H., O'Reilly, K., Pappa, E., Saha, R., Saha, S., Smith, Jenovia Amisti, Knighton, A., Antcliffe, D., Banach, D., Brett, S., Coghlan, P., Fernandez, Z., Gordon, A., Rojo, R., Arias, S. S., Templeton, M., Meredith, M., Morris, L., Ryan, L., Clark, A., Sampson, J., Peters, C., Dent, M., Langley, M., Ashraf, Sana, Wei, S., Andrew, A., Bashyal, A., Davidson, N., Hutton, P., Mckechnie, S., Wilson, J., Baptista, D., Crowe, R., Fernandes, R., Herdman-Grant, R., Joseph, A., O'Connor, D., Allen, M., Loveridge, A., Mckenley, I., Morino, E., Naranjo, A., Simms, R., Sollesta, K., Swain, A., Venkatesh, H., Khera, J., Fox, J., Andrew, G., Barclay, L., Callaghan, M., Campbell, R., Clark, S., Hope, D., Marshall, L., Mcculloch, C., Briton, K., Singleton, J., Birch, S., Brimfield, L., Daly, Z., Pogson, D., Rose, S., Nown, A., Battle, C., Brinkworth, E., Harford, R., Murphy, C., Newey, L., Rees, T., Williams, M., Arnold, S., Polgarova, P., Stroud, K., Meaney, E., Jones, M., Ng, A., Agrawal, S., Pathan, N., White, D., Daubney, E., Elston, K., Grauslyte, L., Hussain, M., Phull, M., Pogreban, T., Rosaroso, L., Salciute, E., Franke, G., Wong, J., George, A., de Gordoa, L. O. -R., Peasgood, E., Phillips, C., Bates, M., Dasgin, J., Gill, J., Nilsson, A., Scriven, J., Collins, A., Khaliq, W., Gude, E. T., Delgado, C. C., Dawson, D., Ding, L., Durrant, G., Ezeobu, O., Farnell-Ward, S., Harrison, A., Kanu, R., Leaver, S., Maccacari, E., Manna, S., Saluzzio, R. P., Queiroz, J., Samakomva, T., Sicat, C., Texeira, J., Da Gloria, E. F., Lisboa, A., Rawlins, J., Mathew, J., Kinch, A., Hurt, W. J., Shah, N., Clark, V., Thanasi, M., Yun, N., Patel, K., Bennett, S., Goodwin, E., Jackson, M., Kent, A., Tibke, C., Woodyatt, W., Zaki, A., Abraheem, A., Bamford, P., Cawley, K., Dunmore, C., Faulkner, M., Girach, R., Jeffrey, H., Jones, R., London, E., Nagra, I., Nasir, F., Sainsbury, H., Smedley, C., Patel, T., Smith, M., Chukkambotla, S., Kazi, A., Hartley, J., Dykes, J., Hijazi, M., Keith, S., Khan, M., Ryan-Smith, J., Springle, P., Thomas, J., Truman, N., Saad, S., Coleman, D., Fine, C., Matt, R., Gay, B., Dalziel, J., Ali, S., Goodchild, D., Harling, R., Bhatterjee, R., Goddard, W., Davison, C., Duberly, S., Hargreaves, J., Bolton, R., Davey, M., Golden, D., Seaman, R., Cherian, S., Cutler, S., Heron, A. E., Roynon-Reed, A., Szakmany, T., Williams, G., Richards, O., Cheema, Y., Brooke, H., Buckley, S., Suarez, J. C., Charlesworth, R., Hansson, K., Norris, J., Poole, A., Rose, A., Sandhu, R., Sloan, B., Smithson, E., Thirumaran, M., Wagstaff, V., Metcalfe, A., Brunton, M., Caterson, J., Coles, H., Frise, M., Rai, S. 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S., Singh, Jaywant, Turner, K., Ellis, H., Stroud, N., Hunt, J., Dearden, J., Dobson, E., Drummond, A., Mulcahy, M., Munt, S., O'Connor, G., Philbin, J., Rishton, C., Tully, R., Winnard, S., Cathcart, S., Duffy, K., Puxty, A., Puxty, K., Turner, L., Ireland, J., Semple, G., Long, K., Whiteley, S., Wilby, E., Ogg, B., Cowton, A., Kay, Abigail, Kent, M., Potts, K., Wilkinson, A., Campbell, S., Brown, E., Melville, J., Naisbitt, J., Joseph, R., Lazo, M., Walton, O., Neal, A., Alexander, P., Allen, S., Bradley-Potts, J., Brantwood, C., Egan, J., Felton, T., Padden, G., Ward, L., Moss, S., Glasgow, S., Abel, L., Brett, M., Digby, B., Gemmell, L., Hornsby, J., Macgoey, P., O'Neil, P., Price, R., Rodden, N., Rooney, K., Sundaram, R., Thomson, N., Hopkins, B., Thrasyvoulou, L., Willis, H., Clark, M., Coulding, M., Jude, E., Mccormick, J., Mercer, O., Potla, D., Rehman, H., Savill, H., Turner, V., Downes, C., Holding, K., Riches, K., Hilton, M., Hayman, M., Subramanian, D., Daniel, P., Adanini, O., Bhatia, N., Msiska, M., Collins, R., Clement, I., Patel, B., Gulati, A., Hays, C., Webster, K., Hudson, A., Webster, A., Stephenson, E., Mccormack, L., Slater, V., Nixon, R., Hanson, H., Fearby, M., Kelly, S., Bridgett, V., Robinson, P., Camsooksai, J., Humphrey, C., Reschreiter, H., Wadams, B., Death, Y., Bastion, V., Clarke, D., David, B., Kent, H., Lorusso, Riccardo, Lubimbi, G., Murdoch, S., Penacerrada, M., Thomas, A., Valentine, J., Vochin, A., Wulandari, R., Djeugam, B., Bell, G., English, K., Katary, A., Wilcox, L., Bruce, M., Connolly, K., Duncan, T., Michael, H. T., Lindergard, G., Hey, S., Fox, C., Alfonso, J., Durrans, L. 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A., Hasanato, R., Al-Awdah, L., Alghamdi, J., Alzahrani, D., Aljohani, S., Al-Afghani, H., Alrashed, M., Aldhawi, N., Albardis, H., Alkwai, S., Alswailm, M., Almalki, F., Albeladi, M., Almohammed, I., Barhoush, E., Albader, A., Massadeh, S., Almalik, A., Alotaibi, S., Alghamdi, B., Jung, J., Fawzy, M. S., Lee, Y., Magnus, P., Trogstad, L. -I. S., Helgeland, O., Harris, J. R., Mangino, M., Spector, T. D., Smieszek, S. P., Przychodzen, B. P., Polymeropoulos, C., Polymeropoulos, V., Polymeropoulos, M. H., Fernandez-Cadenas, I., Perez-Tur, J., Llucia-Carol, L., Cullell, N., Muino, E., Carcel-Marquez, J., Dediego, M. L., Iglesias, L. L., Planas, A. M., Soriano, A., Rico, V., Aguero, D., Bedini, J. L., Lozano, F., Domingo, C., Robles, V., Ruiz-Jaen, F., Marquez, L., Gomez, J., Coto, E., Albaiceta, G. M., Garcia-Clemente, M., Dalmau, D., Arranz, M. J., Dietl, B., Serra-Llovich, A., Soler, P., Colobran, R., Martin-Nalda, A., Martinez, A. P., Bernardo, D., Rojo, S., Fiz-Lopez, A., Arribas, E., de la Cal-Sabater, P., Segura, T., Gonzalez-Villa, E., Serrano-Heras, G., Marti-Fabregas, J., Jimenez-Xarrie, E., Mimbrera, A. F., Masjuan, J., Garcia-Madrona, S., Dominguez-Mayoral, A., Villalonga, J. M., Menendez-Valladares, P., Chasman, D. I., Buring, J. E., Ridker, P. M., Franco, G., Sesso, H. D., Manson, J. E., Glessner, J. R., Hakonarson, H., Medina-Gomez, C., Uitterlinden, A. G., Ikram, M. A., Kristiansson, K., Koskelainen, S., Perola, M., Donner, K., Kivinen, K., Palotie, A., Ripatti, S., Ruotsalainen, S., Kaunisto, M., Nakanishi, T., Butler-Laporte, G., Forgetta, V., Morrison, D. R., Ghosh, B., Laurent, L., Belisle, A., Henry, D., Abdullah, T., Adeleye, O., Mamlouk, N., Kimchi, N., Afrasiabi, Z., Rezk, N., Vulesevic, B., Bouab, M., Guzman, C., Petitjean, L., Tselios, C., Xue, X., Schurr, E., Afilalo, J., Afilalo, M., Oliveira, M., Brenner, B., Lepage, P., Ragoussis, J., Auld, D., Brassard, N., Durand, M., Chasse, M., Kaufmann, D. E., Lathrop, G. M., Mooser, V., Richards, J. B., Li, R., Adra, D., Rahmouni, S., Georges, M., Moutschen, M., Misset, B., Darcis, G., Guiot, J., Guntz, J., Azarzar, S., Gofflot, S., Beguin, Y., Claassen, S., Malaise, O., Huynen, P., Meuris, C., Thys, M., Jacques, J., Leonar, P., Frippiat, F., Giot, J. -B., Sauvage, A. -S., von Frenckell, C., Belhaj, Y., Lambermont, B., Pigazzini, S., Daya, M., Shortt, J., Rafaels, N., Wicks, S. J., Crooks, K., Barnes, K. C., Gignoux, C. R., Chavan, S., Laisk, T., Lall, K., Lepamets, M., Magi, R., Esko, T., Reimann, E., Milani, Luca, Alavere, H., Metsalu, K., Puusepp, M., Metspalu, A., Naaber, P., Laane, E., Pesukova, J., Peterson, P., Kisand, K., Tabri, J., Allos, R., Hensen, K., Starkopf, J., Ringmets, I., Tamm, A., Kallaste, A., Bochud, P. -Y., Rivolta, C., Bibert, S., Quinodoz, M., Kamdar, D., Boillat, N., Nussle, S. G., Albrich, W., Suh, N., Neofytos, D., Erard, V., Voide, C., de Cid, R., Galvan-Femenia, I., Blay, N., Carreras, A., Cortes, B., Farre, X., Sumoy, L., Moreno, V., Mercader, J. M., Guindo-Martinez, M., Torrents, D., Kogevinas, M., Garcia-Aymerich, J., Castano-Vinyals, G., Dobano, C., Renieri, A., Mari, F., Fallerini, C., Daga, S., Benetti, E., Baldassarri, M., Fava, F., Frullanti, E., Valentino, Francesca, Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Beligni, G., Tommasi, A., Sarno, L. D., Palmieri, Marco, Carriero, M. L., Alaverdian, D., Busani, S., Bruno, R., Vecchia, M., Belli, M. A., Picchiotti, N., Sanarico, M., Gori, Mario, Furini, S., Mantovani, Susanna, Ludovisi, S., Mondelli, M. U., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Vaghi, M., Rusconi, S., Siano, M., Montagnani, F., Emiliozzi, A., Fabbiani, M., Rossetti, Barbara, Bargagli, E., Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Bandini, M., Caldarelli, G. P., Piacentini, P., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Pancrazzi, A., Lorubbio, M., Monforte, A. D., Miraglia, F. G., Girardis, M., Venturelli, S., Cossarizza, A., Antinori, Armando, Vergori, A., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Baratti, S., Monica, M. D., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Merla, G., Squeo, G. M., Aucella, F., Raggi, P., Marciano, C., Perna, Raffaella, Bassetti, M., Biagio, A. D., Sanguinetti, Maurizio, Masucci, Luca, Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Coviello, D. A., Mussini, C., Martinelli, E., Mancarella, S., Tavecchia, L., Crotti, L., Gabbi, Chiara, Rizzi, M., Maggiolo, F., Ripamonti, D., Bachetti, T., Rovere, M. T. L., Sarzi-Braga, S., Bussotti, M., Ceri, S., Pinoli, P., Raimondi, F., Biscarini, F., Stella, A., Zguro, K., Capitani, K., Suardi, C., Dei, S., Parati, G., Ravaglia, S., Artuso, R., Botta, Giovanni, Di Domenico, Pasqualina, Rancan, I., Perrella, A., Bianchi, F., Romani, D., Bergomi, P., Catena, E., Colombo, R., Tanfoni, M., Vincenti, A., Ferri, C., Grassi, D., Pessina, Gloria, Tumbarello, Mario, Di Pietro, Maria Luisa, Sabrina, R., Luchi, S., Barbieri, Cristiano, Acquilini, D., Andreucci, E., Segala, F. V., Tiseo, G., Falcone, M., Lista, Maddalena, Poscente, M., De Vivo, O., Petrocelli, Paolo, Guarnaccia, A., Baroni, S., Smith, A. V., Boughton, A. P., Li, K. W., Lefaive, J., Annis, A., Chittoor, G., Josyula, N. S., Leader, J. B., Carey, D. J., Gass, M. C., Cantor, M. N., Yadav, A., van Heel, D. A., Hunt, K. A., Mason, D., Huang, Q. Q., Finer, S., Trivedi, B., Griffiths, C. J., Martin, H. C., Wright, J., Trembath, R. C., Soranzo, N., Zhao, J. H., Butterworth, A. S., Danesh, J., Di Angelantonio, E., Franke, L., Boezen, M., Deelen, P., Claringbould, A., Lopera, E., Warmerdam, R., Vonk, J. M., van Blokland, I., Lanting, P., Ori, A. P. S., Zollner, S., Wang, J., Beck, A., Peloso, G., Ho, Y. -L., Sun, Y. V., Huffman, J. E., O'Donnell, C. J., Cho, K., Tsao, P., Gaziano, J. M., Nivard, M., de Geus, E., Bartels, M., Hottenga, J. J., Weiss, S. T., Karlson, E. W., Smoller, J. W., Green, R. C., Feng, Y. -C. A., Mercader, J., Murphy, S. N., Meigs, J. B., Woolley, A. E., Perez, E. F., Rader, D., Li, B., Verma, S. S., Lucas, A., Bradford, Y., Zeberg, H., Frithiof, R., Hultstrom, M., Lipcsey, M., Tardif, N., Rooyackers, O., Grip, J., Maricic, T., Karczewski, K. J., Atkinson, E. G., Tsuo, K., Baya, N., Turley, P., Gupta, R., Callier, S., Walters, R. K., Palmer, D. S., Sarma, G., Cheng, N., Lu, W., Bryant, S., Churchhouse, C., Cusick, C., Goldstein, J. I., King, D., Seed, C., Finucane, H., Martin, A. R., Satterstrom, F. K., Wilson, D. J., Armstrong, J., Rudkin, J. K., Band, G., Earle, S. G., Lin, S. -K., Arning, N., Crook, D. W., Wyllie, D. H., O'Connell, A. M., Spencer, C. C. A., Koelling, N., Fowler, T., Pasko, D., Ball, C. A., Hong, E. L., Rand, K., Girshick, A., Guturu, H., Baltzell, A. H., Roberts, G., Park, D., Coignet, M., Mccurdy, S., Knight, S., Partha, R., Rhead, B., Zhang, M., Berkowitz, N., Gaddis, M., Noto, K., Ruiz, L., Pavlovic, M., Sloofman, L. G., Charney, A. W., Beckmann, N. D., Schadt, E. E., Jordan, D. M., Thompson, R. C., Gettler, K., Abul-Husn, N. S., Ascolillo, S., Buxbaum, J. D., Chaudhary, K., Cho, J. H., Itan, Y., Kenny, E. E., Belbin, G. M., Sealfon, S. C., Sebra, R. P., Salib, I., Collins, B. L., Levy, T., Britvan, B., Keller, K., Tang, L., Peruggia, M., Hiester, L. L., Niblo, K., Aksentijevich, A., Labkowsky, A., Karp, A., Zlatopolsky, M., Preuss, M., Loos, R. J. F., Nadkarni, G. N., Do, R., Hoggart, C., Choi, S., Underwood, S. J., O'Reilly, P., Huckins, L. M., Zyndorf, M., Daly, M. J., Neale, B. M., Ganna, A., Frater A., Martinez M. L., Smith J., Ashraf S., Singh J., Kay A., Lorusso R., Ali A., Williams H., Barberis L., Wood D. (ORCID:0000-0001-8588-8931), Latif M., Finn S., Taylor A., Tucci A., Adams E. L., Milani L. (ORCID:0000-0003-0218-458X), Valentino F., Mencarelli M. A., Palmieri M. (ORCID:0000-0001-8263-336X), Gori M., Mantovani S., Rossetti B., D'Alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Gabbi C., Botta G., Di Domenico P., Pessina G., Tumbarello M. (ORCID:0000-0002-9519-8552), Di Pietro M. (ORCID:0000-0002-3893-8788), Barbieri C., Lista M., and Petrocelli P.
Abstract: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
Published: 2022

21. Resistance and virulence features of hypermucoviscous Klebsiella pneumoniae from bloodstream infections: Results of a nationwide Italian surveillance study

Author: Arena, F., Menchinelli, Giulia, Di Pilato, V., Torelli, Riccardo, Antonelli, A., Henrici De Angelis, L., Coppi, M., Sanguinetti, Maurizio, Rossolini, G. M., Menchinelli G., Torelli R., Sanguinetti M. (ORCID:0000-0002-9780-7059), Arena, F., Menchinelli, Giulia, Di Pilato, V., Torelli, Riccardo, Antonelli, A., Henrici De Angelis, L., Coppi, M., Sanguinetti, Maurizio, Rossolini, G. M., Menchinelli G., Torelli R., and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Among Enterobacterales, Klebsiella pneumoniae (Kp) is one of the major opportunistic pathogens causing hospital-acquired infections. The most problematic phenomenon linked to Kp is related to the dissemination of multi-drug resistant (MDR) clones producing carbapenem-hydrolyzing enzymes, representing a clinical and public health threat at a global scale. Over the past decades, high-risk MDR clones (e.g., ST512, ST307, ST101 producing blaKPC–type carbepenemases) have become endemic in several countries, including Italy. Concurrently, the spread of highly virulent Kp lineages (e.g., ST23, ST86) able to cause severe, community-acquired, pyogenic infections with metastatic dissemination in immunocompetent subjects has started to be documented. These clones, designated as hypervirulent Kp (hvKp), produce an extensive array of virulence factors and are highly virulent in previously validated animal models. While the prevalence and distribution of MDR Kp has been previously assessed at local and national level knowledge about dissemination of hvKp remains scarce. In this work, we studied the phenotypic and genotypic features of hypermucoviscous (HMV, as possible marker of increased virulence) Kp isolates from bloodstream infections (BSI), obtained in 2016–17 from 43 Italian Laboratories. Antimicrobial susceptibility testing, whole genome sequencing and the use of two animal models (G. mellonella and murine) were employed to characterize collected isolates. Over 1502 BSI recorded in the study period, a total of 19 Kp were selected for further investigation based on their HMV phenotype. Results showed that hvKp isolates (ST5, ST8, ST11, ST25) are circulating in Italy, although with a low prevalence and in absence of a clonal expansion; convergence of virulence (yersiniabactin and/or salmochelin, aerobactin, regulators of mucoid phenotype) and antimicrobial-resistance (extended-spectrum beta-lactamases) features was observed in some cases. Conventional MDR Kp clones (ST307, S
Published: 2022

22. Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function

Author: Galluzzo, Vincenzo, Zazzara, Maria Beatrice, Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, G., Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, F., Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, L., Di Giorgio, A., Nesci, A., Popolla, Valentina, Galluzzo V., Zazzara M. B., Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Tupputi S., Cocchi C., Pirone F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), Popolla V., Galluzzo, Vincenzo, Zazzara, Maria Beatrice, Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, G., Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, F., Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, L., Di Giorgio, A., Nesci, A., Popolla, Valentina, Galluzzo V., Zazzara M. B., Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Tupputi S., Cocchi C., Pirone F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), and Popolla V.
Abstract: Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi-tamins, and plant extracts (Apportal (R)) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal (R) for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one -minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low -flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at
Published: 2022

23. When and which patients should receive remdesivir?

Author: Garcia-Vidal, C., Sanguinetti, Maurizio, Sanguinetti M. (ORCID:0000-0002-9780-7059), Garcia-Vidal, C., Sanguinetti, Maurizio, and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Not available
Published: 2022

24. An explainable model of host genetic interactions linked to COVID-19 severity

Author: Onoja, A., Picchiotti, N., Fallerini, C., Baldassarri, M., Fava, F., Mari, F., Daga, S., Benetti, E., Bruttini, M., Palmieri, Marco, Croci, S., Amitrano, S., Meloni, I., Frullanti, E., Doddato, G., Lista, Maddalena, Beligni, G., Valentino, Francesca, Zguro, K., Tita, R., Giliberti, A., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Ariani, F., Di Sarno, Lorenzo, Montagnani, F., Tumbarello, Mario, Rancan, I., Fabbiani, M., Rossetti, Barbara, Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Romani, D., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Pisani, M., Ognibene, A., Pancrazzi, A., Lorubbio, M., Vaghi, M., D'Arminio Monforte, A., Miraglia, F. G., Bruno, R., Vecchia, M., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Tommasi, A., Zuccon, U., Vietri, L., Scotton, P. G., Andretta, F., Panese, S., Baratti, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Della Monica, M., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Aucella, F., Raggi, P., Perna, Raffaella, Bassetti, M., Di Biagio, Anna, Sanguinetti, Maurizio, Masucci, Luca, Guarnaccia, A., Valente, S., De Vivo, O., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Lacerenza, G., Coviello, D. A., Mussini, C., Martinelli, E., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Sanarico, M., Biscarini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., La Rovere, M. T., Sarzi-Braga, S., Bussotti, M., Capitani, K., Dei, S., Ravaglia, S., Artuso, R., Andreucci, E., Gori, Giovanni Cristiano, Pagliazzi, A., Fiorentini, E., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Luchi, S., Morelli, G., Petrocelli, Paolo, Iacopini, S., Modica, S., Baroni, Silvia, Segala, F. V., Menichetti, F., Falcone, M., Tiseo, G., Barbieri, Cristiano, Matucci, T., Grassi, D., Ferri, C., Marinangeli, F., Brancati, F., Vincenti, A., Borgo, V., Lombardi, S., Lenzi, M., Di Pietro, Maria Luisa, Vichi, F., Romanin, B., Attala, L., Costa, C., Gabbuti, A., Mene, R., Colaneri, M., Casprini, P., Merla, G., Squeo, G. M., Maffezzoni, M., Mantovani, Susanna, Mondelli, M. U., Ludovisi, S., Colombo, F., Chiaromonte, F., Renieri, A., Furini, S., Raimondi, F., Palmieri M. (ORCID:0000-0001-8263-336X), Lista M., Valentino F., Mencarelli M. A., Di Sarno L., Tumbarello M. (ORCID:0000-0002-9519-8552), Rossetti B., D'Alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Di Biagio A., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Gori G. (ORCID:0000-0002-3308-5309), Petrocelli P., Barbieri C., Di Pietro M. A. (ORCID:0000-0002-3893-8788), Mantovani S., Onoja, A., Picchiotti, N., Fallerini, C., Baldassarri, M., Fava, F., Mari, F., Daga, S., Benetti, E., Bruttini, M., Palmieri, Marco, Croci, S., Amitrano, S., Meloni, I., Frullanti, E., Doddato, G., Lista, Maddalena, Beligni, G., Valentino, Francesca, Zguro, K., Tita, R., Giliberti, A., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Ariani, F., Di Sarno, Lorenzo, Montagnani, F., Tumbarello, Mario, Rancan, I., Fabbiani, M., Rossetti, Barbara, Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Romani, D., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Pisani, M., Ognibene, A., Pancrazzi, A., Lorubbio, M., Vaghi, M., D'Arminio Monforte, A., Miraglia, F. G., Bruno, R., Vecchia, M., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Paciosi, F., Tommasi, A., Zuccon, U., Vietri, L., Scotton, P. G., Andretta, F., Panese, S., Baratti, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Della Monica, M., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Aucella, F., Raggi, P., Perna, Raffaella, Bassetti, M., Di Biagio, Anna, Sanguinetti, Maurizio, Masucci, Luca, Guarnaccia, A., Valente, S., De Vivo, O., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Lacerenza, G., Coviello, D. A., Mussini, C., Martinelli, E., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Sanarico, M., Biscarini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., La Rovere, M. T., Sarzi-Braga, S., Bussotti, M., Capitani, K., Dei, S., Ravaglia, S., Artuso, R., Andreucci, E., Gori, Giovanni Cristiano, Pagliazzi, A., Fiorentini, E., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Luchi, S., Morelli, G., Petrocelli, Paolo, Iacopini, S., Modica, S., Baroni, Silvia, Segala, F. V., Menichetti, F., Falcone, M., Tiseo, G., Barbieri, Cristiano, Matucci, T., Grassi, D., Ferri, C., Marinangeli, F., Brancati, F., Vincenti, A., Borgo, V., Lombardi, S., Lenzi, M., Di Pietro, Maria Luisa, Vichi, F., Romanin, B., Attala, L., Costa, C., Gabbuti, A., Mene, R., Colaneri, M., Casprini, P., Merla, G., Squeo, G. M., Maffezzoni, M., Mantovani, Susanna, Mondelli, M. U., Ludovisi, S., Colombo, F., Chiaromonte, F., Renieri, A., Furini, S., Raimondi, F., Palmieri M. (ORCID:0000-0001-8263-336X), Lista M., Valentino F., Mencarelli M. A., Di Sarno L., Tumbarello M. (ORCID:0000-0002-9519-8552), Rossetti B., D'Alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Di Biagio A., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Gori G. (ORCID:0000-0002-3308-5309), Petrocelli P., Barbieri C., Di Pietro M. A. (ORCID:0000-0002-3893-8788), and Mantovani S.
Abstract: We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, supporting their link with COVID-19 severity outcome.
Published: 2022

25. Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function

Author: Galluzzo, Vincenzo, Zazzara, M. B., Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, Giovanni, Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, Federica, Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, Leonardo, Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, Michela, Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, Francesco, Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, Luca, Di Giorgio, Angela, Nesci, Antonio, Popolla, Valentina, Galluzzo V., Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Spaziani G., Tupputi S., Cocchi C., Pirone F., D'Ignazio F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Stella L., Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Sali M. (ORCID:0000-0003-3609-2990), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Lombardi F., Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), Santoro L., Di Giorgio A., Nesci A., Popolla V., Galluzzo, Vincenzo, Zazzara, M. B., Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, Giovanni, Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, Federica, Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, Leonardo, Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, Michela, Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, Francesco, Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, Luca, Di Giorgio, Angela, Nesci, Antonio, Popolla, Valentina, Galluzzo V., Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Spaziani G., Tupputi S., Cocchi C., Pirone F., D'Ignazio F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Stella L., Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Sali M. (ORCID:0000-0003-3609-2990), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Lombardi F., Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), Santoro L., Di Giorgio A., Nesci A., and Popolla V.
Abstract: Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected. Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi- tamins, and plant extracts (Apportal®) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue. Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal® for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one- minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low-flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at t1
Published: 2022

26. Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children

Author: Buonsenso, Danilo, Valentini, Piero, De Rose, Cristina, Tredicine, Maria, Pereyra Boza, Maria Del Carmen, Camponeschi, C., Morello, Rosa, Zampino, Giuseppe, Brooks, A. E. S., Rende, M., Ria, Francesco, Sanguinetti, Maurizio, Delogu, Giovanni, Sali, Michela, Di Sante, Gabriele, Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), De Rose C., Tredicine M., Pereyra Boza M. D. C., Morello R., Zampino G. (ORCID:0000-0003-3865-3253), Ria F. (ORCID:0000-0002-8444-0307), Sanguinetti M. (ORCID:0000-0002-9780-7059), Delogu G. (ORCID:0000-0003-0182-8267), Sali M. (ORCID:0000-0003-3609-2990), Di Sante G. (ORCID:0000-0001-6608-3388), Buonsenso, Danilo, Valentini, Piero, De Rose, Cristina, Tredicine, Maria, Pereyra Boza, Maria Del Carmen, Camponeschi, C., Morello, Rosa, Zampino, Giuseppe, Brooks, A. E. S., Rende, M., Ria, Francesco, Sanguinetti, Maurizio, Delogu, Giovanni, Sali, Michela, Di Sante, Gabriele, Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), De Rose C., Tredicine M., Pereyra Boza M. D. C., Morello R., Zampino G. (ORCID:0000-0003-3865-3253), Ria F. (ORCID:0000-0002-8444-0307), Sanguinetti M. (ORCID:0000-0002-9780-7059), Delogu G. (ORCID:0000-0003-0182-8267), Sali M. (ORCID:0000-0003-3609-2990), and Di Sante G. (ORCID:0000-0001-6608-3388)
Abstract: Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated. Methods. We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9). Results. In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27− naïve B cells, IgD+IgM+ and CD27−IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively). Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026). Conclusions. In this study, we suggest that children affected by Long COVID may have a compromised ability to s
Published: 2022

27. Anti CD20-based immunochemotherapy abolishes antibody response to Covid-19 mRNA vaccine in lymphoma patients vaccinated during active first line treatment

Author: Bellesi, Silvia, Sali, Michela, Maiolo, Maria Elisa, Pereyra Boza, Maria Del Carmen, Alma, Eleonora, Palucci, Ivana, Fatone, Federica, De Maio, Flavio, Viscovo, Marcello, D'Alo, F., De Stefano, Valerio, Hohaus, Stefan, Sanguinetti, Maurizio, Bellesi S., Sali M. (ORCID:0000-0003-3609-2990), Maiolo E., Pereyra Boza M. D. C., Alma E., Palucci I., Fatone F., De Maio F., Viscovo M., De Stefano V. (ORCID:0000-0002-5178-5827), Hohaus S. (ORCID:0000-0002-5534-7197), Sanguinetti M. (ORCID:0000-0002-9780-7059), Bellesi, Silvia, Sali, Michela, Maiolo, Maria Elisa, Pereyra Boza, Maria Del Carmen, Alma, Eleonora, Palucci, Ivana, Fatone, Federica, De Maio, Flavio, Viscovo, Marcello, D'Alo, F., De Stefano, Valerio, Hohaus, Stefan, Sanguinetti, Maurizio, Bellesi S., Sali M. (ORCID:0000-0003-3609-2990), Maiolo E., Pereyra Boza M. D. C., Alma E., Palucci I., Fatone F., De Maio F., Viscovo M., De Stefano V. (ORCID:0000-0002-5178-5827), Hohaus S. (ORCID:0000-0002-5534-7197), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: N/A
Published: 2022

28. Short- and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 in utero or during the perinatal period: preliminary findings

Author: Buonsenso, Danilo, Costa, Simonetta, Giordano, Lucia, Priolo, Francesca, Colonna, A. T., Morini, S., Sbarbati, Martina, Pata, D., Acampora, Anna, Conti, Guido, Crudo, Fabrizio, Cantiani, Alessandro, Martina, Bianca Maria, Amorelli, Giulia Maria, Orazi, Lorenzo, Petrianni, Maria, Ricci, Daniela, Lanzone, Antonio, Sanguinetti, Maurizio, Cattani Franchi, Paola, Sali, Michela, Romeo, Domenico Marco Maurizio, Zampino, Giuseppe, Vento, Giovanni, Valentini, Piero, Buonsenso D., Costa S., Giordano L., Priolo F., Sbarbati M., Acampora A., Conti G. (ORCID:0000-0003-2565-4206), Crudo F., Cantiani A., Martina B. M., Amorelli G. M., Orazi L., Petrianni M., Ricci D., Lanzone A. (ORCID:0000-0003-4119-414X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Sali M. (ORCID:0000-0003-3609-2990), Romeo D. (ORCID:0000-0002-6229-1208), Zampino G. (ORCID:0000-0003-3865-3253), Vento G. (ORCID:0000-0002-8132-5127), Valentini P. (ORCID:0000-0001-6095-9510), Buonsenso, Danilo, Costa, Simonetta, Giordano, Lucia, Priolo, Francesca, Colonna, A. T., Morini, S., Sbarbati, Martina, Pata, D., Acampora, Anna, Conti, Guido, Crudo, Fabrizio, Cantiani, Alessandro, Martina, Bianca Maria, Amorelli, Giulia Maria, Orazi, Lorenzo, Petrianni, Maria, Ricci, Daniela, Lanzone, Antonio, Sanguinetti, Maurizio, Cattani Franchi, Paola, Sali, Michela, Romeo, Domenico Marco Maurizio, Zampino, Giuseppe, Vento, Giovanni, Valentini, Piero, Buonsenso D., Costa S., Giordano L., Priolo F., Sbarbati M., Acampora A., Conti G. (ORCID:0000-0003-2565-4206), Crudo F., Cantiani A., Martina B. M., Amorelli G. M., Orazi L., Petrianni M., Ricci D., Lanzone A. (ORCID:0000-0003-4119-414X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Sali M. (ORCID:0000-0003-3609-2990), Romeo D. (ORCID:0000-0002-6229-1208), Zampino G. (ORCID:0000-0003-3865-3253), Vento G. (ORCID:0000-0002-8132-5127), and Valentini P. (ORCID:0000-0001-6095-9510)
Abstract: The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48–72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48–72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth (P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%). Conclusions: Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of
Published: 2022

29. A real-time integrated framework to support clinical decision making for covid-19 patients

Author: Murri, Rita, Masciocchi, Carlotta, Lenkowicz, Jacopo, Fantoni, Massimo, Damiani, Andrea, Marchetti, A., Sergi, P. D. A., Arcuri, Giovanni, Cesario, Alfredo, Patarnello, S., Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Landolfi, Raffaele, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Murri R. (ORCID:0000-0003-4263-7854), Masciocchi C., Lenkowicz J., Fantoni M. (ORCID:0000-0001-6913-8460), Damiani A., Arcuri G., Cesario A. (ORCID:0000-0003-4687-0709), Antonelli M. (ORCID:0000-0003-3007-1670), Bellantone R. (ORCID:0000-0002-0844-3469), Bernabei R. (ORCID:0000-0002-9197-004X), Boccia S. (ORCID:0000-0002-1864-749X), Calabresi P. (ORCID:0000-0003-0326-5509), Cambieri A., Cauda R. (ORCID:0000-0002-1498-4229), Colosimo C. (ORCID:0000-0003-3800-3648), Crea F. (ORCID:0000-0001-9404-8846), De Maria R. (ORCID:0000-0003-2255-0583), De Stefano V. (ORCID:0000-0002-5178-5827), Franceschi F. (ORCID:0000-0001-6266-445X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Landolfi R. (ORCID:0000-0002-7913-8576), Parolini O. (ORCID:0000-0002-5211-6430), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Urbani A. (ORCID:0000-0001-9168-3174), Zega M. (ORCID:0000-0002-7821-2615), Scambia G. (ORCID:0000-0003-2758-1063), Valentini V. (ORCID:0000-0003-4637-6487), Murri, Rita, Masciocchi, Carlotta, Lenkowicz, Jacopo, Fantoni, Massimo, Damiani, Andrea, Marchetti, A., Sergi, P. D. A., Arcuri, Giovanni, Cesario, Alfredo, Patarnello, S., Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Landolfi, Raffaele, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Murri R. (ORCID:0000-0003-4263-7854), Masciocchi C., Lenkowicz J., Fantoni M. (ORCID:0000-0001-6913-8460), Damiani A., Arcuri G., Cesario A. (ORCID:0000-0003-4687-0709), Antonelli M. (ORCID:0000-0003-3007-1670), Bellantone R. (ORCID:0000-0002-0844-3469), Bernabei R. (ORCID:0000-0002-9197-004X), Boccia S. (ORCID:0000-0002-1864-749X), Calabresi P. (ORCID:0000-0003-0326-5509), Cambieri A., Cauda R. (ORCID:0000-0002-1498-4229), Colosimo C. (ORCID:0000-0003-3800-3648), Crea F. (ORCID:0000-0001-9404-8846), De Maria R. (ORCID:0000-0003-2255-0583), De Stefano V. (ORCID:0000-0002-5178-5827), Franceschi F. (ORCID:0000-0001-6266-445X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Landolfi R. (ORCID:0000-0002-7913-8576), Parolini O. (ORCID:0000-0002-5211-6430), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Urbani A. (ORCID:0000-0001-9168-3174), Zega M. (ORCID:0000-0002-7821-2615), Scambia G. (ORCID:0000-0003-2758-1063), and Valentini V. (ORCID:0000-0003-4637-6487)
Abstract: Background: The COVID-19 pandemic affected healthcare systems worldwide. Predictive models developed by Artificial Intelligence (AI) and based on timely, centralized and standardized real world patient data could improve management of COVID-19 to achieve better clinical outcomes. The objectives of this manuscript are to describe the structure and technologies used to construct a COVID-19 Data Mart architecture and to present how a large hospital has tackled the challenge of supporting daily management of COVID-19 pandemic emergency, by creating a strong retrospective knowledge base, a real time environment and integrated information dashboard for daily practice and early identification of critical condition at patient level. This framework is also used as an informative, continuously enriched data lake, which is a base for several on-going predictive studies. Methods: The information technology framework for clinical practice and research was described. It was developed using SAS Institute software analytics tool and SAS® Vyia® environment and Open-Source environment R ® and Python ® for fast prototyping and modeling. The included variables and the source extraction procedures were presented. Results: The Data Mart covers a retrospective cohort of 5528 patients with SARS-CoV-2 infection. People who died were older, had more comorbidities, reported more frequently dyspnea at onset, had higher D-dimer, C-reactive protein and urea nitrogen. The dashboard was developed to support the management of COVID-19 patients at three levels: hospital, single ward and individual care level. Interpretation: The COVID-19 Data Mart based on integration of a large collection of clinical data and an AI-based integrated framework has been developed, based on a set of automated procedures for data mining and retrieval, transformation and integration, and has been embedded in the clinical practice to help managing daily care. Benefits from the availability of a Data Mart include the oppor
Published: 2022

30. Comparative Fecal Microbiota Analysis of Infants With Acute Bronchiolitis Caused or Not Caused by Respiratory Syncytial Virus

Author: De Maio, Flavio, Buonsenso, Danilo, Bianco, D. M., Giaimo, M., Fosso, B., Monzo, F. R., Sali, Michela, Posteraro, Brunella, Valentini, Piero, Sanguinetti, Maurizio, De Maio F., Buonsenso D., Sali M. (ORCID:0000-0003-3609-2990), Posteraro B. (ORCID:0000-0002-1663-7546), Valentini P. (ORCID:0000-0001-6095-9510), Sanguinetti M. (ORCID:0000-0002-9780-7059), De Maio, Flavio, Buonsenso, Danilo, Bianco, D. M., Giaimo, M., Fosso, B., Monzo, F. R., Sali, Michela, Posteraro, Brunella, Valentini, Piero, Sanguinetti, Maurizio, De Maio F., Buonsenso D., Sali M. (ORCID:0000-0003-3609-2990), Posteraro B. (ORCID:0000-0002-1663-7546), Valentini P. (ORCID:0000-0001-6095-9510), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Bronchiolitis due to respiratory syncytial virus (RSV) or non-RSV agents is a health-menacing lower respiratory tract (LRT) disease of infants. Whereas RSV causes more severe disease than other viral agents may, genus-dominant fecal microbiota profiles have been identified in US hospitalized infants with bronchiolitis. We investigated the fecal microbiota composition of infants admitted to an Italian hospital with acute RSV (25/37 [67.6%]; group I) or non-RSV (12/37 [32.4%]; group II) bronchiolitis, and the relationship of fecal microbiota characteristics with the clinical characteristics of infants. Group I and group II infants differed significantly (24/25 [96.0%] versus 5/12 [41.7%]; P = 0.001) regarding 90% oxygen saturation (SpO2), which is an increased respiratory effort hallmark. Accordingly, impaired feeding in infants from group I was significantly more frequent than in infants from group II (19/25 [76.0%] versus 4/12 [33.3%]; P = 0.04). Conversely, the median (IQR) length of stay was not significantly different between the two groups (seven [3–14] for group I versus five [5–10] for group II; P = 0.11). The 16S ribosomal RNA V3–V4 region amplification of infants’ fecal samples resulted in 299 annotated amplicon sequence variants. Based on alpha- and beta-diversity microbiota downstream analyses, group I and group II infants had similar bacterial communities in their samples. Additionally, comparing infants having <90% SpO2 (n = 29) with infants having ≥90% SpO2 (n = 8) showed that well-known dominant genera (Bacteroides, Bifidobacterium, Escherichia/Shigella, and Enterobacter/Veillonella) were differently, but not significantly (P = 0.44, P = 0.71, P = 0.98, and P = 0.41, respectively) abundant between the two subgroups. Overall, we showed that, regardless of RSV or non-RSV bronchiolitis etiology, no fecal microbiota-composing bacteria could be associated with the severity of acute bronchiolitis in infants. Larger and longitudinally conducted studies wil
Published: 2022

31. 3D-printed graphene polylactic acid devices resistant to SARS-CoV-2: Sunlight-mediated sterilization of additive manufactured objects

Author: De Maio, Flavio, Rosa, Enrico, Perini, Giordano, Augello, A, Niccolini, Benedetta, Ciaiola, F, Santarelli, Giulia, Sciandra, Francesca, Bozzi, Manuela, Sanguinetti, Maurizio, Sali, Michela, De Spirito, Marco, Delogu, Giovanni, Palmieri, Valentina, Papi, Massimiliano, De Maio F, Rosa E, Perini G (ORCID:0000-0001-9452-8479), Niccolini B, Santarelli G, Sciandra F, Bozzi M (ORCID:0000-0002-2656-5849), Sanguinetti M (ORCID:0000-0002-9780-7059), Sali M (ORCID:0000-0003-3609-2990), De Spirito M (ORCID:0000-0003-4260-5107), Delogu G (ORCID:0000-0003-0182-8267), Palmieri V, Papi M (ORCID:0000-0002-0029-1309), De Maio, Flavio, Rosa, Enrico, Perini, Giordano, Augello, A, Niccolini, Benedetta, Ciaiola, F, Santarelli, Giulia, Sciandra, Francesca, Bozzi, Manuela, Sanguinetti, Maurizio, Sali, Michela, De Spirito, Marco, Delogu, Giovanni, Palmieri, Valentina, Papi, Massimiliano, De Maio F, Rosa E, Perini G (ORCID:0000-0001-9452-8479), Niccolini B, Santarelli G, Sciandra F, Bozzi M (ORCID:0000-0002-2656-5849), Sanguinetti M (ORCID:0000-0002-9780-7059), Sali M (ORCID:0000-0003-3609-2990), De Spirito M (ORCID:0000-0003-4260-5107), Delogu G (ORCID:0000-0003-0182-8267), Palmieri V, and Papi M (ORCID:0000-0002-0029-1309)
Abstract: Additive manufacturing has played a crucial role in the COVID-19 global emergency allowing for rapid production of medical devices, indispensable tools for hospitals, or personal protection equipment. However, medical devices, especially in nosocomial environments, represent high touch surfaces prone to viral infection and currently used filaments for 3D printing can't inhibit transmission of virus [1]. Graphene-family materials are capable of reinforcing mechanical, optical and thermal properties of 3D printed constructs. In particular, graphene can adsorb near-infrared light with high efficiency. Here we demonstrate that the addition of graphene nanoplatelets to PLA filaments (PLA-G) allows the creation of 3D-printed devices that can be sterilized by near-infrared light exposure at power density analog to sunlight. This method has been used to kill SARS-CoV-2 viral particles on the surface of 3D printed PLA-G by 3 min of exposure. 3D-printed PLA-G is highly biocompatible and can represent the ideal material for the production of sterilizable personal protective equipment and daily life objects intended for multiple users.
Published: 2022

32. Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates

Author: Bugli, Francesca, Massaro, F., Buonocore, F., Saraceni, P. R., Borocci, S., Ceccacci, F., Bombelli, C., Di Vito, Maura, Marchitiello, R., Mariotti, Melinda, Torelli, Riccardo, Sanguinetti, Maurizio, Porcelli, F., Bugli F. (ORCID:0000-0001-9038-3233), Di Vito M. (ORCID:0000-0002-2991-0855), Mariotti M., Torelli R., Sanguinetti M. (ORCID:0000-0002-9780-7059), Bugli, Francesca, Massaro, F., Buonocore, F., Saraceni, P. R., Borocci, S., Ceccacci, F., Bombelli, C., Di Vito, Maura, Marchitiello, R., Mariotti, Melinda, Torelli, Riccardo, Sanguinetti, Maurizio, Porcelli, F., Bugli F. (ORCID:0000-0001-9038-3233), Di Vito M. (ORCID:0000-0002-2991-0855), Mariotti M., Torelli R., and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and nonmyristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens.
Published: 2022

33. Validation of Two Commercial Multiplex Real-Time PCR Assays for Detection of SARS-CoV-2 in Stool Donors for Fecal Microbiota Transplantation

Author: Di Pilato, V., Morecchiato, F., Rizzato, C., Quaranta, Gianluigi, Fais, R., Gandolfo, Cinzia, Antonelli, A., Cusi, M. G., Pistello, M., Rossolini, G. M., Sanguinetti, Maurizio, Lupetti, A., Masucci, Luca, Quaranta G. (ORCID:0000-0002-8164-4857), Gandolfo C., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Di Pilato, V., Morecchiato, F., Rizzato, C., Quaranta, Gianluigi, Fais, R., Gandolfo, Cinzia, Antonelli, A., Cusi, M. G., Pistello, M., Rossolini, G. M., Sanguinetti, Maurizio, Lupetti, A., Masucci, Luca, Quaranta G. (ORCID:0000-0002-8164-4857), Gandolfo C., Sanguinetti M. (ORCID:0000-0002-9780-7059), and Masucci L. (ORCID:0000-0002-8358-6726)
Abstract: Recurrent infection by Clostridioides difficile has recently been treated by fecal microbiota transplantation (FMT). As viable SARS-CoV-2 was recovered from stool of asymptomatic individuals, the FMT procedure could be a potential risk of SARS-CoV-2 transmission, thus underlying the need to reliably detect SARS-CoV-2 in stool. Here, we performed a multicentric study to explore performances of two commercially available assays for detection of SARS-CoV-2 RNA in stool of potential FMT donors. In three hospitals, 180 stool samples were spiked with serial 10-fold dilutions of a SARS-CoV-2 inactivated lysate to evaluate the Seegene AllplexTM SARS-CoV-2 (SC2) and SARS-CoV-2/FluA/FluB/RSV (SC2FABR) Assays for the detection of viral RNA in stool of FMT donors. The results revealed that both assays detected down to 2 TCID50/mL with comparable limit of detection values, SC2 showing more consistent target positivity rate than SC2FABR. Beyond high amplification efficiency, correlation between CT values and log concentrations of inactivated viral lysates showed R2 values ranging from 0.88 to 0.90 and from 0.87 to 0.91 for the SC2 and SC2FABR assay, respectively. The present results demonstrate that both methods are highly reproducible, sensitive, and accurate for SARS-CoV-2 RNA detection in stool, suggesting a potential use in FMT-donor screening.
Published: 2022

34. Anti-Mold Effectiveness of a Green Emulsion Based on Citrus aurantium Hydrolate and Cinnamomum zeylanicum Essential Oil for the Modern Paintings Restoration

Author: Di Vito, Maura, Vergari, L., Mariotti, Melinda, Proto, M. R., Barbanti, L., Garzoli, S., Sanguinetti, Maurizio, Sabatini, L., Peduzzi, A., Bellardi, M. G., Mattarelli, P., Bugli, Francesca, De Luca, D., Di Vito M. (ORCID:0000-0002-2991-0855), Mariotti M., Sanguinetti M. (ORCID:0000-0002-9780-7059), Bugli F. (ORCID:0000-0001-9038-3233), Di Vito, Maura, Vergari, L., Mariotti, Melinda, Proto, M. R., Barbanti, L., Garzoli, S., Sanguinetti, Maurizio, Sabatini, L., Peduzzi, A., Bellardi, M. G., Mattarelli, P., Bugli, Francesca, De Luca, D., Di Vito M. (ORCID:0000-0002-2991-0855), Mariotti M., Sanguinetti M. (ORCID:0000-0002-9780-7059), and Bugli F. (ORCID:0000-0001-9038-3233)
Abstract: A modern painting is characterized by multi-material bases extremely exposed to biodeteri-ogenic attacks. The aim of this work was to test the antifungal effectiveness of a natural, eco-friendly, and safe emulsion based on Citrus aurantium L. var. amara hydrolate and Cinnamomum zeylanicum Blume (from bark) essential oil, named “Zeylantium green emulsion” (Zege), on modern paintings. Colored unaged and aged canvas samples, performed with modern techniques (acrylic, vinylic and alkyd), were used to test in vitro both the antifungal effectiveness of Zege and its impact on the chemical–physical characteristics. Microbiological tests were performed according to the EUCAST international guidelines. pH measurements and colorimetric analysis were performed on unaged and aged canvases before and after Zege spray treatment. Finally, in situ tests were performed using the spray emulsion on canvas samples obtained from Ilaria Margutti’s modern artwork, which had been colonized by molds. Microbiological tests on canvas prototypes showed a time-and dose-dependent effectiveness of the Zege spray. None of the techniques underwent relevant changes in pH. Only the acrylic colors were unaffected in the colorimetric analysis, among all colored unaged or aged canvases. Tests made with modern artwork samples confirmed the in situ antifungal effectiveness. The Zege spray showed encouraging results in regard to the use of this formulation in the restoration of modern paintings.
Published: 2022

35. Setting-specific variability of false-positive result rates with rapid testing for SARS-CoV-2 antigen

Author: Posteraro, P., Errico, F. M., De Carolis, A., Menchinelli, Giulia, Sanguinetti, Maurizio, Posteraro, Brunella, Menchinelli G., Sanguinetti M. (ORCID:0000-0002-9780-7059), Posteraro B. (ORCID:0000-0002-1663-7546), Posteraro, P., Errico, F. M., De Carolis, A., Menchinelli, Giulia, Sanguinetti, Maurizio, Posteraro, Brunella, Menchinelli G., Sanguinetti M. (ORCID:0000-0002-9780-7059), and Posteraro B. (ORCID:0000-0002-1663-7546)
Abstract: Not available
Published: 2022

36. Characteristic of IgA and IgG antibody response to SARS-CoV-2 infection in an Italian referral COVID-19 Hospital

Author: Carnicelli, A., Fiori, B., Ricci, Rosalba, Piano, A., Bonadia, N., Taddei, Eleonora, Fantoni, Massimo, Murri, Rita, Cingolani, Antonella, Barillaro, Christian, Cutuli, S. L., Marchesini, Debora, Della Polla, D. A., Forte, E., Fuorlo, M., Di Maurizio, L., Amorini, Paola, Cattani, P., Franceschi, Francesco, Sanguinetti, Maurizio, Ricci R., Taddei E., Fantoni M. (ORCID:0000-0001-6913-8460), Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Barillaro C., Marchesini D., Amorini P., Franceschi F. (ORCID:0000-0001-6266-445X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Carnicelli, A., Fiori, B., Ricci, Rosalba, Piano, A., Bonadia, N., Taddei, Eleonora, Fantoni, Massimo, Murri, Rita, Cingolani, Antonella, Barillaro, Christian, Cutuli, S. L., Marchesini, Debora, Della Polla, D. A., Forte, E., Fuorlo, M., Di Maurizio, L., Amorini, Paola, Cattani, P., Franceschi, Francesco, Sanguinetti, Maurizio, Ricci R., Taddei E., Fantoni M. (ORCID:0000-0001-6913-8460), Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Barillaro C., Marchesini D., Amorini P., Franceschi F. (ORCID:0000-0001-6266-445X), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Introduction: Antibody response plays a fundamental role in the natural history of infectious disease. A better understanding of the immune response in patients with SARS-CoV-2 infection could be important for identifying patients at greater risk of developing a more severe form of disease and with a worse prognosis. Methods: We performed a cross-sectional analysis to determine the presence and the levels of both anti-SARS-CoV-2 IgG and IgA in a cohort of hospitalized patients with confirmed infection at different times in the natural history of the disease. Patients enrolled when admitted at the emergency department were prospectively followed up during hospital stay. Results: Overall, 131 patients were considered with a total of 237 samples processed. Cross-sectional analysis showed that seroconversion for IgA seems to occur between days 6 and 15, while IgG response seems to occur slightly later, peaking at day 20 after symptoms onset. Both IgA and IgG were maintained beyond 2 months. Severe patients showed a higher IgA response compared with mild patients when analyzing optical density (8.3 versus 5.6, p < 0.001). Prospective analysis conducted on 55 patients confirmed that IgA appear slightly earlier than IgG. After stratifying for the severity of disease, both the IgA and IgG responses were more vigorous in severe cases. Moreover, while IgG tended to stabilize, there was a relevant decline after the first month of IgA levels in mild cases. Conclusion: IgA and IgG antibody response is closely related, although seroconversion for IgA occurs earlier. Both IgA and IgG are maintained beyond 2 months. Severe patients showed a more vigorous IgA and IgG response. IgA levels seem to decline after 1 month since the onset of symptoms in mild cases. Our results should be interpreted with cautions due to several limitations in our study, mainly the small number of cases, lack of data on viral load and clinical setting.
Published: 2022

37. Il Silenzio: The First Renaissance Oil Painting on Canvas from the Uffizi Museum Restored with a Safe, Green Antimicrobial Emulsion Based on Citrus aurantium var. amara Hydrolate and Cinnamomum zeylanicum Essential Oil

Author: Minotti, D., Vergari, L., Proto, M. R., Barbanti, L., Garzoli, S., Bugli, Francesca, Sanguinetti, Maurizio, Sabatini, L., Peduzzi, A., Rosato, R., Bellardi, M. G., Mattarelli, P., De Luca, D., Di Vito, Maura, Bugli F. (ORCID:0000-0001-9038-3233), Sanguinetti M. (ORCID:0000-0002-9780-7059), Di Vito M. (ORCID:0000-0002-2991-0855), Minotti, D., Vergari, L., Proto, M. R., Barbanti, L., Garzoli, S., Bugli, Francesca, Sanguinetti, Maurizio, Sabatini, L., Peduzzi, A., Rosato, R., Bellardi, M. G., Mattarelli, P., De Luca, D., Di Vito, Maura, Bugli F. (ORCID:0000-0001-9038-3233), Sanguinetti M. (ORCID:0000-0002-9780-7059), and Di Vito M. (ORCID:0000-0002-2991-0855)
Abstract: Preserving artworks from the attacks of biodeteriogens is a primary duty of humanity. Nowadays, restorers use chemicals potentially dangerous for both artworks and human health. The purpose of this work was to find a green and safe formulation based on natural substances with fungicidal activity to restore ancient oil paintings, particularly “Il Silenzio” (by Jacopo Zucchi) preserved at the Uffizi Museum in Florence, Italy. The study was divided into two phases. First phase (in vitro study): three essential oils (EOs) and four hydrolates (Hys) were analysed by GC-mass spectrometry and in vitro tested against six ATCC strains of molds. An emulsion based on the more active natural compounds was tested on aged and unaged canvases samples to evaluate both their fungicidal activity and the impact on chemical-physical parameters. Finally, an in vivo toxicity test performed on the Galleria mellonella model assessed the safety for health. Second phase (in situ application): the emulsion was sprayed on the back of the painting and left to act for 24 h. Biodeteriogens present on the “Il Silenzio” painting were microbiologically identified before and after the treatment. The emulsion formulated with C. zeylanicum EO and C. aurantium var. amara Hy showed the best antifungal activity both in vitro and in situ without altering the chemical-physical characteristics of paintings. Furthermore, no in vivo toxicity was shown. For the first time, a green antimicrobial emulsion based on Hy and EO, safe for operators, was used to decontaminate an artwork colonised by fungi before the restoration practices.
Published: 2022

38. SARS-CoV-2 viral load and replication in postmortem examinations

Author: Grassi, S., Arena, Vincenzo, Cattani, P., Dell'Aquila, Marco, Liotti, Flora Marzia, Sanguinetti, Maurizio, Oliva, Antonio, Arena V. (ORCID:0000-0002-7562-223X), Dell'Aquila M., Liotti F. M., Sanguinetti M. (ORCID:0000-0002-9780-7059), Oliva A. (ORCID:0000-0001-7120-616X), Grassi, S., Arena, Vincenzo, Cattani, P., Dell'Aquila, Marco, Liotti, Flora Marzia, Sanguinetti, Maurizio, Oliva, Antonio, Arena V. (ORCID:0000-0002-7562-223X), Dell'Aquila M., Liotti F. M., Sanguinetti M. (ORCID:0000-0002-9780-7059), and Oliva A. (ORCID:0000-0001-7120-616X)
Abstract: We examined 29 autopsy cases (investigated between October 2020 and February 2021) whose postmortem swabs tested positive for SARS-CoV-2. Twenty-two of 29 cases died while hospitalized (H), while the remaining 7 cases were not hospitalized (NH). Since we included only cases in which the time since death was known (excluding unwitnessed NH deaths), the interval between death and postmortem swab(s) was registered, with a mean NH value of 5.50 days and a mean H value of 3.98 days. The mean age of NH was 65 years, while H were older (mean age: 73 years). Twenty-eight nasopharyngeal and 27 lungs postmortem swabs were obtained and real-time reverse transcriptase‒polymerase chain reaction assay for total and replicative SARS-CoV-2 RNA and mRNA detection was performed. Although the mean death-postmortem swabs interval was higher in NH than in H, the mean viral load of NH was higher than that of H (2.53 × 1011 copies/mL vs 9.31 × 108 copies/mL). In 13/29 cases (6 NH and 7 H), indicators of active replication were found. The relationship between the presence of replicative mRNA and death without hospitalization and that between the minimum cycle threshold value of SARS-CoV-2 RNA and the cycle threshold value of replicative SARS-CoV-2 mRNA were found to be statistically significant (with respective P values of 0.013 and 0.000). Therefore, especially in NH, full compliance with guidelines on biological safety in the autopsy room is essential, and no autopsy can be performed on infected cases in a structure that does not meet the established safety criteria.
Published: 2022

39. Old and New Insights into Sporothrix schenckii Complex Biology and Identification

Author: De Carolis, Elena, Posteraro, Brunella, Sanguinetti, Maurizio, De Carolis E. (ORCID:0000-0003-4757-7256), Posteraro B. (ORCID:0000-0002-1663-7546), Sanguinetti M. (ORCID:0000-0002-9780-7059), De Carolis, Elena, Posteraro, Brunella, Sanguinetti, Maurizio, De Carolis E. (ORCID:0000-0003-4757-7256), Posteraro B. (ORCID:0000-0002-1663-7546), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Sporothrix schenckii is a worldwide-distributed thermally dimorphic fungus, which usually causes a subacute to chronic infection through traumatic implantation or inoculation of its infectious propagules. The fungus encompasses a group of phylogenetically closely related species, thus named the S. schenckii complex, of which S. schenckii sensu stricto and S. brasiliensis are main causative species of sporotrichosis. Owing to a multifaceted molecular dynamic, the S. schenckii complex can switch between the mycelium and the yeast form. This characteristic along with a varying cell wall composition account for significant species-specific differences in the host range, virulence, and susceptibility to antifungal drugs. While culture remains the gold standard to diagnose sporotrichosis, polymerase chain reaction (PCR) or matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry-based methods have become an essential for accurate species identification in many clinical laboratories. If directly applied on tissue samples, molecular methods are helpful to improve both sensitivity of and time to the etiological diagnosis of sporotrichosis. This mini-review aims to put together the old and new knowledge on the S. schenckii complex biology and identification, with particular emphasis on the laboratory diagnosis-related aspects of dis-ease.
Published: 2022

40. Inactivation of the Response Regulator AgrA Has a Pleiotropic Effect on Biofilm Formation, Pathogenesis and Stress Response in Staphylococcus lugdunensis

Author: Aubourg, M., Pottier, M., Leon, A., Bernay, B., Dhalluin, A., Cacaci, Margherita, Torelli, Riccardo, Ledormand, P., Martini, C., Sanguinetti, Maurizio, Auzou, M., Gravey, F., Giard, J. -C., Cacaci M. (ORCID:0000-0002-5433-9400), Torelli R. (ORCID:0000-0003-1956-3981), Sanguinetti M. (ORCID:0000-0002-9780-7059), Aubourg, M., Pottier, M., Leon, A., Bernay, B., Dhalluin, A., Cacaci, Margherita, Torelli, Riccardo, Ledormand, P., Martini, C., Sanguinetti, Maurizio, Auzou, M., Gravey, F., Giard, J. -C., Cacaci M. (ORCID:0000-0002-5433-9400), Torelli R. (ORCID:0000-0003-1956-3981), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Staphylococcus lugdunensis is a coagulase-negative Staphylococcus that emerges as an important opportunistic pathogen. However, little is known about the regulation underlying the transition from commensal to virulent state. Based on knowledge of S. aureus virulence, we suspected that the agr quorum sensing system may be an important determinant for the pathogenicity of S. lugdunensis. We investigated the functions of the transcriptional regulator AgrA using the agrA deletion mutant. AgrA played a role in cell pigmentation: DargA mutant colonies were white while the parental strains were slightly yellow. Compared with the wild-type strain, the DargA mutant was affected in its ability to form biofilm and was less able to survive in mice macrophages. Moreover, the growth of DagrA was significantly reduced by the addition of 10% NaCl or 0.4 mM H2O2 and its survival after 2 h in the presence of 1 mM H2O2 was more than 10-fold reduced. To explore the mechanisms involved beyond these phenotypes, the DagrA proteome and transcriptome were characterized by mass spectrometry and RNA-Seq. We found that AgrA controlled several virulence factors as well as stress-response factors, which are well correlated with the reduced resistance of the DagrA mutant to osmotic and oxidative stresses. These results were not the consequence of the deregulation of RNAIII of the agr system, since no phenotype or alteration of the proteomic profile has been observed for the DRNAIII mutant. Altogether, our results highlighted that the AgrA regulator of S. lugdunensis played a key role in its ability to become pathogenic.
Published: 2022

41. Identification and molecular characterization of Subramaniula asteroides causing human fungal keratitis: a case report

Author: Cultrera, R., Torelli, R. (ORCID:0000-0003-1956-3981), Sarnicola, C., Segala, D., Mengoli, A., Chiaretto, G., Perri, P., Sanguinetti, M. (ORCID:0000-0002-9780-7059), Cultrera, R., Torelli, R. (ORCID:0000-0003-1956-3981), Sarnicola, C., Segala, D., Mengoli, A., Chiaretto, G., Perri, P., and Sanguinetti, M. (ORCID:0000-0002-9780-7059)
Abstract: Background: Keratitis due to by filamentous fungi are not easy to diagnose thus causing a delay in correct therapy. There are many descriptions of keratitis due to Candida, Fusarium and Aspergillus genera. Subramaniula genus has only recently been reported to cause human infections and there are few descriptions of eye infections due to this filamentous fungus. Diagnosis of fungal keratitis is usually based on microscopic and cultural techniques of samples obtained by corneal swabbing or scraping. Considering the amount of time required to obtain culture results it is wise to use other diagnostic methods, such as molecular analyses. Therapeutic options against these fungi are limited by low tissue penetration in the eye due to ocular barriers. We describe the first case of S. asteroides human keratitis treated with isavuconazole. Case presentation: We describe a rare case of fungal keratitis unresponsive to antimicrobial treatment in a 65-year-old male patient without a history of diabetes or immunological diseases. He reported that the onset of symptoms occurred during a long holiday in Cape Verde Island. Initial treatment with topical antibiotics associated to steroids were ineffective, allowing a slow clinical progression of disease to corneal perforation. On admission in our Hospital, slit-lamp examination of the left eye showed conjunctival congestion and hyperemia, a large inferior corneal ulceration with brown pigment, corneal edema, about 3 mm of hypopyon and irido-lenticular synechiae. The slow clinical progression of the disease to corneal perforation and the aspect of the ulcer were consistent with a mycotic etiology. Molecular methods used on fungal colonies isolated by Sabouraud’s dextrose agar cultures allowed the identification of Subramaniula asteroids from corneal scraping. Antimicrobial test showed a good susceptibility of this filamentous fungus to voriconazole and isavuconazole. Moreover, this fungal keratitis was successfully treated with isavuc
Published: 2021

42. COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes

Author: MacDonald, L., Alivernini, S. (ORCID:0000-0002-7383-4212), Tolusso, B., Elmesmari, A., Somma, D., Perniola, S., Paglionico, A., Petricca, L., Bosello, S. L. (ORCID:0000-0002-4837-447X), Carfi, A., Sali, M., Stigliano, E., Cingolani, A. (ORCID:0000-0002-3793-2755), Murri, R. (ORCID:0000-0003-4263-7854), Arena, V. (ORCID:0000-0002-7562-223X), Fantoni, M., Antonelli, M. (ORCID:0000-0003-3007-1670), Landi, F. (ORCID:0000-0002-3472-1389), Franceschi, F., Sanguinetti, M. (ORCID:0000-0002-9780-7059), McInnes, I. B., McSharry, C., Gasbarrini, A. (ORCID:0000-0002-7278-4823), Otto, T. D., Kurowska-Stolarska, M., Gremese, E. (ORCID:0000-0002-2248-1058), MacDonald, L., Alivernini, S. (ORCID:0000-0002-7383-4212), Tolusso, B., Elmesmari, A., Somma, D., Perniola, S., Paglionico, A., Petricca, L., Bosello, S. L. (ORCID:0000-0002-4837-447X), Carfi, A., Sali, M., Stigliano, E., Cingolani, A. (ORCID:0000-0002-3793-2755), Murri, R. (ORCID:0000-0003-4263-7854), Arena, V. (ORCID:0000-0002-7562-223X), Fantoni, M., Antonelli, M. (ORCID:0000-0003-3007-1670), Landi, F. (ORCID:0000-0002-3472-1389), Franceschi, F., Sanguinetti, M. (ORCID:0000-0002-9780-7059), McInnes, I. B., McSharry, C., Gasbarrini, A. (ORCID:0000-0002-7278-4823), Otto, T. D., Kurowska-Stolarska, M., and Gremese, E. (ORCID:0000-0002-2248-1058)
Abstract: We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post–COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post–COVID-19 pathology.
Published: 2021

43. Vaccine-induced thrombotic thrombocytopenia, a rare but severe case of friendly fire in the battle against COVID-19 pandemic: What pathogenesis?

Author: De Cristofaro, R., Sanguinetti, M., De Cristofaro R. (ORCID:0000-0002-8066-8849), Sanguinetti M. (ORCID:0000-0002-9780-7059), De Cristofaro, R., Sanguinetti, M., De Cristofaro R. (ORCID:0000-0002-8066-8849), and Sanguinetti M. (ORCID:0000-0002-9780-7059)
Abstract: Not available
Published: 2021

44. Seroprevalence of sars-cov-2 antibodies in hiv-infected patients in rome, italy during the covid-19 outbreak

Author: Lombardi, F., Ricci, R., Belmonti, S., Fabbiani, M., Borghetti, A., Baldin, G., Ciccullo, A., Tamburrini, E., Visconti, E., Sanguinetti, M., Di Giambenedetto, S., Lombardi F. (ORCID:0000-0001-5757-8346), Ricci R., Borghetti A., Tamburrini E. (ORCID:0000-0003-4930-426X), Visconti E., Sanguinetti M. (ORCID:0000-0002-9780-7059), Di Giambenedetto S. (ORCID:0000-0001-6990-5076), Lombardi, F., Ricci, R., Belmonti, S., Fabbiani, M., Borghetti, A., Baldin, G., Ciccullo, A., Tamburrini, E., Visconti, E., Sanguinetti, M., Di Giambenedetto, S., Lombardi F. (ORCID:0000-0001-5757-8346), Ricci R., Borghetti A., Tamburrini E. (ORCID:0000-0003-4930-426X), Visconti E., Sanguinetti M. (ORCID:0000-0002-9780-7059), and Di Giambenedetto S. (ORCID:0000-0001-6990-5076)
Abstract: Background: this study aimed to determine the proportion of people living with HIV (PLWH) with anti-SARS-CoV-2 IgG antibodies in a large sample from a single HIV referral center in Rome, Italy; the time-frame included both the first and the second wave of the Italian COVID-19 pandemic; Methods: we conducted a cross-sectional study on stored cryopreserved samples from 1 March 2020 to 30 November 2020. Total antibodies against SARS-CoV-2 were preliminarily tested using a chemiluminescent immunoassay. Positive results were re-tested with an ELISA assay as an IgG confirmatory test; Results: overall, 1389 samples were analyzed from 1106 PLWH: 69% males, median age 53 years, 94% on antiretroviral treatment, 93% with HIV-RNA < 50 copies/mL, median CD4 cell count 610 cell/µL. Our analysis revealed a total of n = 8 patients who tested IgG positive during the study period. Seroprevalence was equal to 0% in the first months (March–June); this started to increase in July and reached a maximum rate of 1.59% in October 2020. The overall seroprevalence was 0.72% (8/1106, 95% CI 0.37–1.42). Conclusion: our findings from this setting show a low IgG SARS-CoV-2 prevalence among PLWH as compared to data available from the general population.
Published: 2021

45. C9orf72 intermediate repeats confer genetic risk for severe covid-19 pneumonia independently of age

Author: Zanella, I., Zacchi, E., Piva, S., Filosto, M., Beligni, G., Alaverdian, D., Amitrano, S., Fava, F., Baldassarri, M., Frullanti, E., Meloni, I., Renieri, A., Castelli, F., Quiros-Roldan, E., Mari, F., Daga, S., Benetti, E., Furini, S., Fallerini, C., Valentino, Francesca, Doddato, G., Giliberti, A., Tita, R., Bruttini, M., Croci, S., Pinto, A. M., Mencarelli, Marta, Rizzo, C. L., Montagnani, F., Tumbarello, Mario, Rancan, I., Sarno, L. D., Palmieri, Marco, Carriero, M. L., Fabbiani, M., Rossetti, Barbara, Bargagli, E., Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canac-Cini, A., Verzuri, A., Anemoli, V., Ognibene, A., Pancrazi, A., Lorubbio, M., Vaghi, M., Monforte, A. D., Miraglia, F. G., Mondelli, M. U., Bruno, R., Marco, V., Mantovani, Susanna, Ludovisi, S., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Tommasi, A., Paciosi, F., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Antoni, M. D., Monica, M. D., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Merla, G., Squeo, G. M., Aucella, F., Raggi, P., Marciano, C., Perna, Raffaella, Bassetti, M., Biagio, A. D., Sanguinetti, Maurizio, Masucci, Luca, Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Coviello, D. A., Mussini, C., Bosio, Giacomo, Martinelli, E., Mancarella, S., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Picchiotti, N., Gori, Mario, Gabbi, Chiara, Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Bis-Carini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., Rovere, M. T. L., Sarzi-Braga, S., Bussotti, M., Capitani, K., Zguro, K., Dei, S., Ravaglia, S., Artuso, R., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Perticaroli, V., Gennarelli, Massimo, Magri, Carlotta, Basiotto, G., Zizioli, D., Giliani, S., Monti, E., Foca, E., Carriero, C., Latronico, N., Padovani, A., Brugnoni, D., Valentino F., Mencarelli M. A., Tumbarello M. (ORCID:0000-0002-9519-8552), Palmieri M. (ORCID:0000-0001-8263-336X), Rossetti B., D'alessandro M., Franchi F., Donati A., Mantovani S., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Bosio G., Gori M., Gabbi C., Gennarelli M., Magri C., Zanella, I., Zacchi, E., Piva, S., Filosto, M., Beligni, G., Alaverdian, D., Amitrano, S., Fava, F., Baldassarri, M., Frullanti, E., Meloni, I., Renieri, A., Castelli, F., Quiros-Roldan, E., Mari, F., Daga, S., Benetti, E., Furini, S., Fallerini, C., Valentino, Francesca, Doddato, G., Giliberti, A., Tita, R., Bruttini, M., Croci, S., Pinto, A. M., Mencarelli, Marta, Rizzo, C. L., Montagnani, F., Tumbarello, Mario, Rancan, I., Sarno, L. D., Palmieri, Marco, Carriero, M. L., Fabbiani, M., Rossetti, Barbara, Bargagli, E., Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Raffaelli, C. S., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canac-Cini, A., Verzuri, A., Anemoli, V., Ognibene, A., Pancrazi, A., Lorubbio, M., Vaghi, M., Monforte, A. D., Miraglia, F. G., Mondelli, M. U., Bruno, R., Marco, V., Mantovani, Susanna, Ludovisi, S., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Tommasi, A., Paciosi, F., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Antoni, M. D., Monica, M. D., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Merla, G., Squeo, G. M., Aucella, F., Raggi, P., Marciano, C., Perna, Raffaella, Bassetti, M., Biagio, A. D., Sanguinetti, Maurizio, Masucci, Luca, Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Coviello, D. A., Mussini, C., Bosio, Giacomo, Martinelli, E., Mancarella, S., Tavecchia, L., Belli, M. A., Crotti, L., Parati, G., Picchiotti, N., Gori, Mario, Gabbi, Chiara, Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Bis-Carini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., Rovere, M. T. L., Sarzi-Braga, S., Bussotti, M., Capitani, K., Zguro, K., Dei, S., Ravaglia, S., Artuso, R., Perrella, A., Bianchi, F., Bergomi, P., Catena, E., Colombo, R., Perticaroli, V., Gennarelli, Massimo, Magri, Carlotta, Basiotto, G., Zizioli, D., Giliani, S., Monti, E., Foca, E., Carriero, C., Latronico, N., Padovani, A., Brugnoni, D., Valentino F., Mencarelli M. A., Tumbarello M. (ORCID:0000-0002-9519-8552), Palmieri M. (ORCID:0000-0001-8263-336X), Rossetti B., D'alessandro M., Franchi F., Donati A., Mantovani S., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Bosio G., Gori M., Gabbi C., Gennarelli M., and Magri C.
Abstract: A cytokine storm, autoimmune features and dysfunctions of myeloid cells significantly contribute to severe coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Genetic background of the host seems to be partly responsible for severe phenotype and genes related to innate immune response seem critical host determinants. The C9orf72 gene has a role in vesicular trafficking, autophagy regulation and lyso-some functions, is highly expressed in myeloid cells and is involved in immune functions, regulating the lysosomal degradation of mediators of innate immunity. A large non-coding hexanucleotide repeat expansion (HRE) in this gene is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), both characterized by neuroinflammation and high systemic levels of proinflammatory cytokines, while HREs of intermediate length, although rare, are more frequent in autoimmune disorders. C9orf72 full mutation results in haploinsufficiency and intermediate HREs seem to modulate gene expression as well and impair autophagy. Herein, we sought to explore whether intermediate HREs in C9orf72 may be a risk factor for severe COVID-19. Although we found intermediate HREs in only a small portion of 240 patients with severe COVID-19 pneumonia, the magnitude of risk for requiring non-invasive or mechanical ventilation conferred by harboring intermediate repeats >10 units in at least one C9orf72 allele was more than twice respect to having shorter expansions, when adjusted for age (odds ratio (OR) 2.36; 95% confidence interval (CI) 1.04–5.37, p = 0.040). The association between intermediate repeats >10 units and more severe clinical outcome (p = 0.025) was also validated in an independent cohort of 201 SARS-CoV-2 infected patients. These data suggest that C9orf72 HREs >10 units may influence the pathogenic process driving more severe COVID-19 phenotypes.
Published: 2021

46. Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study

Author: Fallerini, C., Daga, S., Mantovani, Susanna, Benetti, E., Picchiotti, N., Francisci, D., Paciosi, F., Schiaroli, E., Baldassarri, M., Fava, F., Palmieri, Marco, Ludovisi, S., Castelli, F., Quiros-Roldan, E., Vaghi, M., Rusconi, S., Siano, M., Bandini, M., Spiga, O., Capitani, K., Furini, S., Mari, F., Renieri, A., Mondelli, M. U., Frullanti, E., Valentino, Francesca, Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Sarno, L. D., Beligni, G., Tommasi, A., Iuso, N., Montagnani, F., Fabbiani, M., Rossetti, Barbara, Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Romani, D., Piacentini, P., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., D'Arminio Monforte, A., Miraglia, F. G., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Gabrieli, A., Riva, A., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Baratti, S., Antoni, M. D., Monica, M. D., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Merla, G., Squeo, G. M., Aucella, F., Raggi, P., Marciano, C., Perna, Raffaella, Bassetti, M., Biagio, A. D., Sanguinetti, Maurizio, Masucci, Luca, Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Coviello, D. A., Mussini, C., Bosio, Giacomo, Martinelli, E., Mancarella, S., Tavecchia, L., Gori, Mario, Crotti, L., Parati, G., Gabbi, Chiara, Zanella, I., Rizzi, M., Maggiolo, F., Ripamonti, D., Bachetti, T., Rovere, M. T. L., Sarzi-Braga, S., Bussotti, M., Chiariello, M., Belli, M. A., Dei, S., Mantovani S., Palmieri M. (ORCID:0000-0001-8263-336X), Valentino F., Mencarelli M. A., Rossetti B., D'alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Bosio G., Gori M., Gabbi C., Fallerini, C., Daga, S., Mantovani, Susanna, Benetti, E., Picchiotti, N., Francisci, D., Paciosi, F., Schiaroli, E., Baldassarri, M., Fava, F., Palmieri, Marco, Ludovisi, S., Castelli, F., Quiros-Roldan, E., Vaghi, M., Rusconi, S., Siano, M., Bandini, M., Spiga, O., Capitani, K., Furini, S., Mari, F., Renieri, A., Mondelli, M. U., Frullanti, E., Valentino, Francesca, Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Mencarelli, Marta, Rizzo, C. L., Pinto, A. M., Sarno, L. D., Beligni, G., Tommasi, A., Iuso, N., Montagnani, F., Fabbiani, M., Rossetti, Barbara, Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, Michele, Cameli, P., Bennett, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, Francesca, Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, Andrea, Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Romani, D., Piacentini, P., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., D'Arminio Monforte, A., Miraglia, F. G., Girardis, M., Venturelli, S., Busani, S., Cossarizza, A., Antinori, Armando, Vergori, A., Emiliozzi, A., Gabrieli, A., Riva, A., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Baratti, S., Antoni, M. D., Monica, M. D., Piscopo, C., Capasso, Monica, Russo, R., Andolfo, I., Iolascon, A., Fiorentino, Giuseppe, Carella, M., Castori, M., Merla, G., Squeo, G. M., Aucella, F., Raggi, P., Marciano, C., Perna, Raffaella, Bassetti, M., Biagio, A. D., Sanguinetti, Maurizio, Masucci, Luca, Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Trotta, T., Giannattasio, F., Coiro, G., Lena, Francesco, Coviello, D. A., Mussini, C., Bosio, Giacomo, Martinelli, E., Mancarella, S., Tavecchia, L., Gori, Mario, Crotti, L., Parati, G., Gabbi, Chiara, Zanella, I., Rizzi, M., Maggiolo, F., Ripamonti, D., Bachetti, T., Rovere, M. T. L., Sarzi-Braga, S., Bussotti, M., Chiariello, M., Belli, M. A., Dei, S., Mantovani S., Palmieri M. (ORCID:0000-0001-8263-336X), Valentino F., Mencarelli M. A., Rossetti B., D'alessandro M., Franchi F., Donati A., Antinori A. (ORCID:0000-0002-6019-2417), Capasso M., Fiorentino G., Perna R., Sanguinetti M. (ORCID:0000-0002-9780-7059), Masucci L. (ORCID:0000-0002-8358-6726), Lena F. (ORCID:0000-0001-5528-319X), Bosio G., Gori M., and Gabbi C.
Abstract: Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients. Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (<60 y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene.
Published: 2021

47. Residual respiratory impairment after COVID-19 pneumonia

Author: Lombardi, F., Calabrese, Anna Chiara, Iovene, Bruno, Pierandrei, C., Lerede, M., Varone, Francesco, Richeldi, Luca, Sgalla, Giacomo, Landi, Francesco, Gremese, Elisa, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Romano Settanni, C., Benvenuto, F., Bramato, Giulia, Carfi, A., Ciciarello, Francesca, Lo Monaco, Maria Rita, Maria Martone, A., Marzetti, Emanuele, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tosato, Matteo, Tritto, M., Calvani, Riccardo, Catalano, Lucio, Picca, A., Savera, Giulia, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Assunta Zocco, M., Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Bizzarro, Alessandra, Lauria, Alessandra, Rizzo, Stanislao, Cristina Savastano, M., Gambini, Gloria, Grazia Cozzupoli, M., Culiersi, Carola, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Sani, Gabriele, Janiri, Delfina, Giuseppin, G., Molinaro, M., Modica, Marco, Natale, Luigi, Rita Larici, A., Marano, Riccardo, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Laur, a. Fedele A., Maria Lizzio, M., Santoliquido, Angelo, Santoro, L., Nesci, A., Popolla, Valentina, Calabrese A., Iovene B., Varone F., Richeldi L. (ORCID:0000-0001-8594-1448), Sgalla G. (ORCID:0000-0003-3130-9388), Landi F. (ORCID:0000-0002-3472-1389), Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Bramato G., Ciciarello F., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Marzetti E. (ORCID:0000-0001-9567-6983), Pagano F., Rocchi S., Salerno A., Tosato M., Calvani R. (ORCID:0000-0001-5472-2365), Catalano L., Savera G., Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Gambini G., Culiersi C., Cesare Passali G. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Modica M., Natale L. (ORCID:0000-0002-7949-5119), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Santoliquido A. (ORCID:0000-0003-1539-4017), Popolla V., Lombardi, F., Calabrese, Anna Chiara, Iovene, Bruno, Pierandrei, C., Lerede, M., Varone, Francesco, Richeldi, Luca, Sgalla, Giacomo, Landi, Francesco, Gremese, Elisa, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Romano Settanni, C., Benvenuto, F., Bramato, Giulia, Carfi, A., Ciciarello, Francesca, Lo Monaco, Maria Rita, Maria Martone, A., Marzetti, Emanuele, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tosato, Matteo, Tritto, M., Calvani, Riccardo, Catalano, Lucio, Picca, A., Savera, Giulia, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Assunta Zocco, M., Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Bizzarro, Alessandra, Lauria, Alessandra, Rizzo, Stanislao, Cristina Savastano, M., Gambini, Gloria, Grazia Cozzupoli, M., Culiersi, Carola, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Sani, Gabriele, Janiri, Delfina, Giuseppin, G., Molinaro, M., Modica, Marco, Natale, Luigi, Rita Larici, A., Marano, Riccardo, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Laur, a. Fedele A., Maria Lizzio, M., Santoliquido, Angelo, Santoro, L., Nesci, A., Popolla, Valentina, Calabrese A., Iovene B., Varone F., Richeldi L. (ORCID:0000-0001-8594-1448), Sgalla G. (ORCID:0000-0003-3130-9388), Landi F. (ORCID:0000-0002-3472-1389), Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Bramato G., Ciciarello F., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Marzetti E. (ORCID:0000-0001-9567-6983), Pagano F., Rocchi S., Salerno A., Tosato M., Calvani R. (ORCID:0000-0001-5472-2365), Catalano L., Savera G., Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Gambini G., Culiersi C., Cesare Passali G. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Modica M., Natale L. (ORCID:0000-0002-7949-5119), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Santoliquido A. (ORCID:0000-0003-1539-4017), and Popolla V.
Abstract: Introduction: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. Method: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). Results: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. Conclusion: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.
Published: 2021

48. Lumipulse G SARS-CoV-2 Ag assay evaluation using clinical samples from different testing groups

Author: Menchinelli, Giulia, Bordi, L., Liotti, Flora Marzia, Palucci, Ivana, Capobianchi, M. R., Sberna, G., Lalle, E., Romano, Lucio, De Angelis, Giulia, Marchetti, Simona, Sanguinetti, Maurizio, Cattani, P., Posteraro, Brunella, Menchinelli G., Liotti F. M., Palucci I., Romano L., de Angelis G. (ORCID:0000-0002-7087-7399), Marchetti S., Sanguinetti M. (ORCID:0000-0002-9780-7059), Posteraro B. (ORCID:0000-0002-1663-7546), Menchinelli, Giulia, Bordi, L., Liotti, Flora Marzia, Palucci, Ivana, Capobianchi, M. R., Sberna, G., Lalle, E., Romano, Lucio, De Angelis, Giulia, Marchetti, Simona, Sanguinetti, Maurizio, Cattani, P., Posteraro, Brunella, Menchinelli G., Liotti F. M., Palucci I., Romano L., de Angelis G. (ORCID:0000-0002-7087-7399), Marchetti S., Sanguinetti M. (ORCID:0000-0002-9780-7059), and Posteraro B. (ORCID:0000-0002-1663-7546)
Abstract: Objectives: Compared to RT-PCR, lower performance of antigen detection assays, including the Lumipulse G SARS-CoV-2 Ag assay, may depend on specific testing scenarios. Methods: We tested 594 nasopharyngeal swab samples from individuals with COVID-19 (RT-PCR cycle threshold [Ct] values ≤ 40) or non-COVID-19 (Ct values > 40) diagnoses. RT-PCR positive samples were assigned to diagnostic, screening, or monitoring groups of testing. Results: With a limit of detection of 1.2 × 104 SARS-CoV-2 RNA copies/ml, Lumipulse showed positive percent agreement (PPA) of 79.9% (155/194) and negative percent agreement of 99.3% (397/400), whereas PPAs were 100% for samples with Ct values of <18 or 18–<25 and 92.5% for samples with Ct values of 25–<30. By three groups, Lumipulse showed PPA of 87.0% (60/69), 81.1% (43/53), or 72.2% (52/72), respectively, whereas PPA was 100% for samples with Ct values of <18 or 18–<25, and was 94.4, 80.0, or 100% for samples with Ct values of 25–<30, respectively. Additional testing of RT-PCR positive samples for SARS-CoV-2 subgenomic RNA showed that, by three groups, PPA was 63.8% (44/69), 62.3% (33/53), or 33.3% (24/72), respectively. PPAs dropped to 55.6, 20.0, or 41.7% for samples with Ct values of 25–<30, respectively. All 101 samples with a subgenomic RNA positive result had a Lumipulse assay’s antigen positive result, whereas only 54 (58.1%) of remaining 93 samples had a Lumipulse assay’s antigen positive result. Conclusions: Lumipulse assay was highly sensitive in samples with low RT-PCR Ct values, implying repeated testing to reduce consequences of false-negative results.
Published: 2021

49. Should face masks be worn to contain the spread of COVID-19 in the postlockdown phase?

Author: Landi, Francesco, Marzetti, Emanuele, Sanguinetti, Maurizio, Ciciarello, Francesca, Tritto, M., Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., D'Angelo, Emanuela, Fusco, Domenico, Lo Monaco, Maria Rita, Martone, Anna Maria, Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Russo, Andrea, Salerno, A., Cattani Franchi, Paola, Marchetti, S., Bernabei, Roberto, Landi F (ORCID:0000-0002-3472-1389), Marzetti E (ORCID:0000-0001-9567-6983), Sanguinetti M (ORCID:0000-0002-9780-7059), Ciciarello F, Bramato G., Brandi V., D'Angelo E., Fusco D., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F., Rocchi S., Russo A., Cattani P. (ORCID:0000-0003-4678-4763), Bernabei R (ORCID:0000-0002-9197-004X), Landi, Francesco, Marzetti, Emanuele, Sanguinetti, Maurizio, Ciciarello, Francesca, Tritto, M., Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., D'Angelo, Emanuela, Fusco, Domenico, Lo Monaco, Maria Rita, Martone, Anna Maria, Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Russo, Andrea, Salerno, A., Cattani Franchi, Paola, Marchetti, S., Bernabei, Roberto, Landi F (ORCID:0000-0002-3472-1389), Marzetti E (ORCID:0000-0001-9567-6983), Sanguinetti M (ORCID:0000-0002-9780-7059), Ciciarello F, Bramato G., Brandi V., D'Angelo E., Fusco D., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F., Rocchi S., Russo A., Cattani P. (ORCID:0000-0003-4678-4763), and Bernabei R (ORCID:0000-0002-9197-004X)
Abstract: Background: In East Asia, face masks are commonly worn to reduce viral spread. In Euope and North America, however, their use has been stigmatised for a long time, although this view has radically changed during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Notwithstanding this, it is still unclear whether face masks worn by COVID-19 carriers may indeed prevent viral transmission and environmental contamination. The objective of this study was to evaluate the effectiveness of surgical face masks in filtering SARS-CoV-2. Methods: Four male patients with COVID-19 were recruited for the study. Two patients wore a surgical mask for 5 h, while two others did not. The spread of the virus in the environment was evaluated through the approved Allplex 2019-nCoV assay. Results: In the room with the two patients without surgical masks, the swab performed on the headboard and sides of the beds was positive for SARS-CoV-2 contamination. In the other room, where two patients were wearing surgical masks, all of the swabs obtained after 5 h tested negative. Conclusions: The results of the current study add to the growing body of literature supporting the use of face masks as a measure to contain the spread of SARS-CoV-2 by retaining potentially contagious droplets that can infect other people and/or contaminate surfaces. Based on the current evidence, face masks should therefore be considered a useful and low-cost device in addition to social distancing and hand hygiene during the postlockdown phase.
Published: 2021

50. Reply to: Individuality of the composition of the human microbiota

Author: Natalello, G., Bosello, Silvia Laura, Sanguinetti, Maurizio, Gremese, Elisa, Bosello S. L. (ORCID:0000-0002-4837-447X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Gremese E. (ORCID:0000-0002-2248-1058), Natalello, G., Bosello, Silvia Laura, Sanguinetti, Maurizio, Gremese, Elisa, Bosello S. L. (ORCID:0000-0002-4837-447X), Sanguinetti M. (ORCID:0000-0002-9780-7059), and Gremese E. (ORCID:0000-0002-2248-1058)
Abstract: NA
Published: 2021

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