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Summary Background The emerging threat represented by SARS-CoV-2 variants, demands the development of therapies for better clinical management of COVID-19. MAD0004J08 is an extremely potent Fc-engineered monoclonal antibody (mAb) able to neutralise in vitro all current SARS-CoV-2 variants of concern (VoCs). This ongoing study, evaluates safety, pharmacokinetics and SARS-CoV-2 sera neutralization effect of MAD0004J08 when administered as single dose intramuscularly in healthy adults. Method We conducted a dose escalation study with sequential enrolment of three cohorts, each with an increasing dose level of MAD0004J08 (48mg, 100mg and 400mg). Within each cohort, 10 young healthy adults were randomized with 4:1 ratio to a single intramuscular (i.m.) injection of MAD0004J08 or placebo. The primary endpoint is the proportion of subjects with severe and/or serious treatment emergent adverse events (TEAEs) within 7 days post-treatment. Secondary endpoints reported in this paper are the proportion of subjects with solicited TEAEs up 7 days post dosing, MAD0004J08 serum concentrations and neutralising activity versus the original SARS-COV-2 Wuhan virus at different timepoints post-dosing. As post-hoc analyses, we compared the sera neutralising titres of subjects who received MAD0004J08 with those of people that had received the COVID-19 BNT162b2 mRNA vaccine in the previous sixty days (n=10) and COVID-19 convalescent patients (n=20), and assessed serum neutralisation activity against the B.1.1.7 (alpha), B.1.351 (beta) and B.1.1.248 (gamma) SARS-CoV-2 variants of concern. Findings A total of 30 subjects, 10 per cohort, were enrolled and randomized. Data up to 30 days were available and analysed in this report. No severe TEAEs were reported in any of the cohorts in the 7 days post-treatment. MAD0004J08 was detected in the sera of treated subjects within few hours post-administration and reached almost maximal levels on day 8. The geometric mean neutralising titres (GMT) assessed against the original Wuhan virus peaked on day 8 and ranged 226 – 905, 905 – 2,560, and 1,280 – 5,120 for cohort 1, 2 and 3 respectively. The sera neutralising GMT in MAD0004J08 treated subjects in all the three cohorts were found to be 1·5-54·5-fold higher compared to sera from convalescent patients and 1·83– 76·4-fold higher compared to sera from COVID-19 vaccinees. Finally, GMT in MAD0004J08 treated subjects showed high neutralising titres versus the B.1.1.7 (alpha), B.1.351 (beta) and B.1.1.248 (gamma) SARS-CoV-2 VoCs. Interpretation A single dose administration of MAD0004J08 via i.m. route is safe and well tolerated and results in a rapid systemic distribution of the MAD0004J08 and sera neutralising titres higher than COVID-19 convalescent and vaccinated subjects. A single dose administration of MAD0004J08 is also sufficient to effectively neutralise major SARS-CoV-2 variants of concern. Based on these results, a Phase 2-3 trial is ongoing to further assess the safety, dosage, and efficacy of MAD0004J08 in asymptomatic or mild-moderate symptomatic COVID-19 patients. Funding EU Malaria Fund, Ministero dello Sviluppo Economico, Ministero della Salute, Regione Toscana, Toscana Life Sciences Sviluppo and European Research Council. Research in context Evidence before this study We searched PUBMED, MEDLINE and MedRxiv for clinical trials, meta-analyses and randomized controlled trials evaluating the antibody neutralization titres vs. different SARS-CoV-2 variants of concern obtained from subjects who received monoclonal antibodies for the treatment of COVID-19 using the following search terms: (“COVID-19” OR “SARS-CoV-2”) AND (“monoclonal antibody” OR “neutralising antibody”) AND (“variants” OR “variants of concern”). No relevant studies were identified. Added value of this study This is the first human study assessing safety, PK and neutralising potential of MAD0004J08, a monoclonal antibody against SARS-CoV-2 wild type Wuhan virus and variants of concern, administered intramuscularly at low dosages (48, 100 and 400 mg). MAD0004J08 showed to be safe and well tolerated in the tested dose range. Anti-spike antibodies were detected in the sera of tested SARS-CoV-2 negative healthy adults few hours post-injection. In addition, the sera obtained from MAD0004J08treated subjects, showed to have high neutralisation titres against the Wuhan virus, the B.1.1.7 (alpha), B.1.351 (beta) and B.1.1.248 (gamma) variants of concern. Implications of all the available evidence A potent monoclonal antibody such as MAD0004J08, capable of neutralising multiple variants of concern of SARS-CoV-2 rapidly and long lastingly when given as a single intramuscular injection. The antibody, presently tested in a phase 2-3 efficacy trial, can be a major advancement in the prophylaxis and clinical management of COVID-19, because of its broad spectrum, ease of use in non-hospital settings and economic sustainability.
Simone Lanini; Stefano Milleri; Emanuele Andreano; Sarah Nosari; Ida Paciello; Giulia Piccini; Alessandra Gentili; Adhuna Phogat; Inesa Hyseni; Margherita Leonardi; Alessandro Torelli; Emanuele Montomoli; Andrea Paolini; Andrea Frosini; Andrea Antinori; Emanuele Nicastri; Enrico Girardi; Maria Maddalena Plazzi; Giuseppe Ippolito; Francesco Vaia; Giovanni Della Cioppa; Rino Rappuoli. A single intramuscular injection of monoclonal antibody MAD0004J08 induces in healthy adults SARS-CoV-2 neutralising antibody titres exceeding those induced by infection and vaccination. 2021, 1 .
AMA StyleSimone Lanini, Stefano Milleri, Emanuele Andreano, Sarah Nosari, Ida Paciello, Giulia Piccini, Alessandra Gentili, Adhuna Phogat, Inesa Hyseni, Margherita Leonardi, Alessandro Torelli, Emanuele Montomoli, Andrea Paolini, Andrea Frosini, Andrea Antinori, Emanuele Nicastri, Enrico Girardi, Maria Maddalena Plazzi, Giuseppe Ippolito, Francesco Vaia, Giovanni Della Cioppa, Rino Rappuoli. A single intramuscular injection of monoclonal antibody MAD0004J08 induces in healthy adults SARS-CoV-2 neutralising antibody titres exceeding those induced by infection and vaccination. . 2021; ():1.
Chicago/Turabian StyleSimone Lanini; Stefano Milleri; Emanuele Andreano; Sarah Nosari; Ida Paciello; Giulia Piccini; Alessandra Gentili; Adhuna Phogat; Inesa Hyseni; Margherita Leonardi; Alessandro Torelli; Emanuele Montomoli; Andrea Paolini; Andrea Frosini; Andrea Antinori; Emanuele Nicastri; Enrico Girardi; Maria Maddalena Plazzi; Giuseppe Ippolito; Francesco Vaia; Giovanni Della Cioppa; Rino Rappuoli. 2021. "A single intramuscular injection of monoclonal antibody MAD0004J08 induces in healthy adults SARS-CoV-2 neutralising antibody titres exceeding those induced by infection and vaccination." , no. : 1.
Background: The benefits and timing of percutaneous dilatational tracheostomy (PDT) in Intensive Care Unit (ICU) COVID-19 patients are still controversial. PDT is considered a high-risk procedure for the transmission of SARS-CoV-2 to healthcare workers (HCWs). The present study analyzed the optimal timing of PDT, the clinical outcomes of patients undergoing PDT, and the safety of HCWs performing PDT. Methods: Of the 133 COVID-19 patients who underwent PDT in our ICU from 1 April 2020 to 31 March 2021, 13 patients were excluded, and 120 patients were enrolled. A trained medical team was dedicated to the PDT procedure. Demographic, clinical history, and outcome data were collected. Patients who underwent PDT were stratified into two groups: an early group (PDT ≤ 12 days after orotracheal intubation (OTI) and a late group (>12 days after OTI). An HCW surveillance program was also performed. Results: The early group included 61 patients and the late group included 59 patients. The early group patients had a shorter ICU length of stay and fewer days of mechanical ventilation than the late group (p< 0.001). On day 7 after tracheostomy, early group patients required fewer intravenous anesthetic drugs and experienced an improvement of the ventilation parameters PaO2/FiO2 ratio, PEEP, and FiO2 (p< 0.001). No difference in the case fatality ratio between the two groups was observed. No SARS-CoV-2 infections were reported in the HCWs performing the PDTs. Conclusions: PDT was safe and effective for COVID-19 patients since it improved respiratory support parameters, reduced ICU length of stay and duration of mechanical ventilation, and optimized the weaning process. The procedure was safe for all HCWs involved in the dedicated medical team. The development of standardized early PDT protocols should be implemented, and PDT could be considered a first-line approach in ICU COVID-19 patients requiring prolonged mechanical ventilation.
Nardi Tetaj; Micaela Maritti; Giulia Stazi; Maria Marini; Daniele Centanni; Gabriele Garotto; Ilaria Caravella; Cristina Dantimi; Matteo Fusetti; Carmen Santagata; Manuela Macchione; Giada De Angelis; Filippo Giansante; Donatella Busso; Rachele Di Lorenzo; Silvana Scarcia; Alessandro Carucci; Ricardo Cabas; Ilaria Gaviano; Nicola Petrosillo; Andrea Antinori; Fabrizio Palmieri; Gianpiero D’Offizi; Stefania Ianniello; Paolo Campioni; Francesco Pugliese; Francesco Vaia; Emanuele Nicastri; Giuseppe Ippolito; Luisa Marchioni; ICU COVID-19 Study Group. Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients over a Year in the Intensive Care Unit. Journal of Clinical Medicine 2021, 10, 3335 .
AMA StyleNardi Tetaj, Micaela Maritti, Giulia Stazi, Maria Marini, Daniele Centanni, Gabriele Garotto, Ilaria Caravella, Cristina Dantimi, Matteo Fusetti, Carmen Santagata, Manuela Macchione, Giada De Angelis, Filippo Giansante, Donatella Busso, Rachele Di Lorenzo, Silvana Scarcia, Alessandro Carucci, Ricardo Cabas, Ilaria Gaviano, Nicola Petrosillo, Andrea Antinori, Fabrizio Palmieri, Gianpiero D’Offizi, Stefania Ianniello, Paolo Campioni, Francesco Pugliese, Francesco Vaia, Emanuele Nicastri, Giuseppe Ippolito, Luisa Marchioni, ICU COVID-19 Study Group. Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients over a Year in the Intensive Care Unit. Journal of Clinical Medicine. 2021; 10 (15):3335.
Chicago/Turabian StyleNardi Tetaj; Micaela Maritti; Giulia Stazi; Maria Marini; Daniele Centanni; Gabriele Garotto; Ilaria Caravella; Cristina Dantimi; Matteo Fusetti; Carmen Santagata; Manuela Macchione; Giada De Angelis; Filippo Giansante; Donatella Busso; Rachele Di Lorenzo; Silvana Scarcia; Alessandro Carucci; Ricardo Cabas; Ilaria Gaviano; Nicola Petrosillo; Andrea Antinori; Fabrizio Palmieri; Gianpiero D’Offizi; Stefania Ianniello; Paolo Campioni; Francesco Pugliese; Francesco Vaia; Emanuele Nicastri; Giuseppe Ippolito; Luisa Marchioni; ICU COVID-19 Study Group. 2021. "Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients over a Year in the Intensive Care Unit." Journal of Clinical Medicine 10, no. 15: 3335.
Introduction: The use of steroid therapy in patients within the context of SARS-CoV-2 infection is still a matter of debate. This study aimed to evaluate if potential steroid benefits could be predicted by the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2) (P/F) in COVID-19 patients at admission. Materials and Methods: Medical records were retrospectively collected from all adult patients admitted because of COVID-19 from 29 January to 31 July 2020. The association of steroid therapy with 28-day all-cause mortality outcome was analysed in a multivariable logistic regression model adjusted for confounding factors. Results: Overall, 511 patients were analysed, of which 39.1% underwent steroid therapy. Steroid treated patients were mostly male, older, and more frequently treated with antiviral drugs and aminoquinolines; the most common comorbidities were hypertension, followed by cardiovascular disease. Overall, 51 patients died within 28-days, and overall 28-days mortality was 19.5% in the cohort of patients exposed to steroids versus 3.9% mortality in unexposed patients (p< 0.001). Steroid therapy on patients with P/F ratio of 235 mmHg or higher at admission can be considered as detrimental, with an 8% increased probability of death. Conclusions: Steroid therapy is associated with increased 28-day mortality in COVID-19 in patients with mild or no ARDS.
Serena Vita; Daniele Centanni; Simone Lanini; Pierluca Piselli; Silvia Rosati; Maria Giancola; Annalisa Mondi; Carmela Pinnetti; Simone Topino; Pierangelo Chinello; Silvia Mosti; Gina Gualano; Francesca Faraglia; Fabio Iacomi; Luisa Marchioni; Micaela Maritti; Enrico Girardi; Giuseppe Ippolito; Emanuele Nicastri; on behalf of the ReCOVeRI Study Group. Benefits of Steroid Therapy in COVID-19 Patients with Different PaO2/FiO2 Ratio at Admission. Journal of Clinical Medicine 2021, 10, 3236 .
AMA StyleSerena Vita, Daniele Centanni, Simone Lanini, Pierluca Piselli, Silvia Rosati, Maria Giancola, Annalisa Mondi, Carmela Pinnetti, Simone Topino, Pierangelo Chinello, Silvia Mosti, Gina Gualano, Francesca Faraglia, Fabio Iacomi, Luisa Marchioni, Micaela Maritti, Enrico Girardi, Giuseppe Ippolito, Emanuele Nicastri, on behalf of the ReCOVeRI Study Group. Benefits of Steroid Therapy in COVID-19 Patients with Different PaO2/FiO2 Ratio at Admission. Journal of Clinical Medicine. 2021; 10 (15):3236.
Chicago/Turabian StyleSerena Vita; Daniele Centanni; Simone Lanini; Pierluca Piselli; Silvia Rosati; Maria Giancola; Annalisa Mondi; Carmela Pinnetti; Simone Topino; Pierangelo Chinello; Silvia Mosti; Gina Gualano; Francesca Faraglia; Fabio Iacomi; Luisa Marchioni; Micaela Maritti; Enrico Girardi; Giuseppe Ippolito; Emanuele Nicastri; on behalf of the ReCOVeRI Study Group. 2021. "Benefits of Steroid Therapy in COVID-19 Patients with Different PaO2/FiO2 Ratio at Admission." Journal of Clinical Medicine 10, no. 15: 3236.
The COVID-19 pandemic has produced an extraordinary care setting where physicians played, and continue to play, a critical role in containing viral spread and treating affected patients. Frontline workers have been receiving day-to-day new information about therapeutic advances. The purpose of the study is to analyse COVID-19 drug consumption trends in both acute and intensive care settings comparing Defined Daily Doses and the release of scientific clinical data from January to December 2020.
Serena Vita; Dora Forliano; Aldo De Luca; Alessia Beccacece; Luisa Marchioni; Emanuele Nicastri; on behalf of the COVID-19 INMI Study Group. Drug Policies Skyline during COVID-19 Pandemic. Journal of Clinical Medicine 2021, 10, 3117 .
AMA StyleSerena Vita, Dora Forliano, Aldo De Luca, Alessia Beccacece, Luisa Marchioni, Emanuele Nicastri, on behalf of the COVID-19 INMI Study Group. Drug Policies Skyline during COVID-19 Pandemic. Journal of Clinical Medicine. 2021; 10 (14):3117.
Chicago/Turabian StyleSerena Vita; Dora Forliano; Aldo De Luca; Alessia Beccacece; Luisa Marchioni; Emanuele Nicastri; on behalf of the COVID-19 INMI Study Group. 2021. "Drug Policies Skyline during COVID-19 Pandemic." Journal of Clinical Medicine 10, no. 14: 3117.
(1) Background: Benefits and timing of percutaneous dilatational tracheostomy (PDT) in Intensive Care Unit (ICU) COVID-19 patients are still controversial. PDT is considered a high risk procedure for transmission of SARS CoV-2 to health care workers (HCWs). The present study analyzed optimal timing of PDT, clinical outcomes of patients undergoing PDT and safety of HCWs performing PDT. (2) Methods: 133 COVID-19 patients underwent PDT in our ICU from April 1, 2020 to March 31, 2021, 23 patients were excluded and 110 patients were enrolled. A trained medical team was dedicated to the PDT procedure. Demographic, clinical history and outcome data were collected. Patients who underwent PDT were stratified into two groups: early group, PDT ≤ 12 days from orotracheal-intubation (OTI) and late group, >12 days from OTI; HCW surveillance program was performed. (3) Results: Early group included 57 patients and late group included 53 patients. Early group patients showed shorter ICU length of stay and fewer days of mechanical ventilation than the late group (p<0.001). At day 7 after tracheostomy, early group patients required fewer intravenous anesthetic drugs and experienced an improvement of ventilation parameters, PaO2/FiO2-Ratio, PEEP and FiO2 (p<0.001). No difference in case fatality ratio between the two groups was reported. No SARS-CoV-2 infection was reported in HCWs performing PDT. (4) Conclusions: PDT was safe and effective for COVID-19 patients, since it improved respiratory support parameters, reduced ICU length of stay and duration of mechanical ventilation, and optimized the weaning process. The procedure was safe for all HCWs involved in the dedicated medical team. The development of standardized early PDT protocols should be implemented and PDT procedure could be considered as first line approach in ICU COVID-19 requiring prolonged mechanical ventilation.
Nardi Tetaj; Micaela Maritti; Giulia Stazi; Maria Cristina Marini; Daniele Centanni; Gabriele Garotto; Ilaria Caravella; Cristina Dantimi; Matteo Fusetti; Carmen Santagata; Manuela Macchione; Giada De Angelis; Filippo Giansante; Donatella Busso; Rachele Di Lorenzo; Silvana Scarcia; Alessandro Carucci; Ricardo Cabas; Ilaria Gaviano; Nicola Petrosillo; Andrea Antinori; Fabrizio Palmieri; Gianpiero D'Offizi; Stefania Ianniello; Paolo Campioni; Francesco Pugliese; Francesco Vaia; Emanuele Nicastri; Giuseppe Ippolito; Luisa Marchioni. Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients Over a Year in Intensive Care Unit. 2021, 1 .
AMA StyleNardi Tetaj, Micaela Maritti, Giulia Stazi, Maria Cristina Marini, Daniele Centanni, Gabriele Garotto, Ilaria Caravella, Cristina Dantimi, Matteo Fusetti, Carmen Santagata, Manuela Macchione, Giada De Angelis, Filippo Giansante, Donatella Busso, Rachele Di Lorenzo, Silvana Scarcia, Alessandro Carucci, Ricardo Cabas, Ilaria Gaviano, Nicola Petrosillo, Andrea Antinori, Fabrizio Palmieri, Gianpiero D'Offizi, Stefania Ianniello, Paolo Campioni, Francesco Pugliese, Francesco Vaia, Emanuele Nicastri, Giuseppe Ippolito, Luisa Marchioni. Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients Over a Year in Intensive Care Unit. . 2021; ():1.
Chicago/Turabian StyleNardi Tetaj; Micaela Maritti; Giulia Stazi; Maria Cristina Marini; Daniele Centanni; Gabriele Garotto; Ilaria Caravella; Cristina Dantimi; Matteo Fusetti; Carmen Santagata; Manuela Macchione; Giada De Angelis; Filippo Giansante; Donatella Busso; Rachele Di Lorenzo; Silvana Scarcia; Alessandro Carucci; Ricardo Cabas; Ilaria Gaviano; Nicola Petrosillo; Andrea Antinori; Fabrizio Palmieri; Gianpiero D'Offizi; Stefania Ianniello; Paolo Campioni; Francesco Pugliese; Francesco Vaia; Emanuele Nicastri; Giuseppe Ippolito; Luisa Marchioni. 2021. "Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients Over a Year in Intensive Care Unit." , no. : 1.
Objectives To investigate the association between sex hormones and the severity of coronavirus disease 2019 (COVID-19). Furthermore, associations between sex hormones and systemic inflammation markers, viral shedding and length of hospital stay were studied. Design and methods This case–control study included a total of 48 male patients with COVID-19 admitted to an Italian reference hospital. The 24 cases were patients with PaO2/FiO2 300 mmHg at all times and who may have required low-flow oxygen supplementation during hospitalization (mild COVID-19). For each group, sex hormones were evaluated on hospital admission. Results Patients with severe COVID-19 (cases) had a significantly lower testosterone level compared with patients with mild COVID-19 (controls). Median total testosterone (TT) was 1.4 ng/mL in cases and 3.5 ng/mL in controls (P = 0.005); median bioavailable testosterone (BioT) was 0.49 and 1.21 in cases and controls, respectively (P = 0.008); and median calculated free testosterone (cFT) was 0.029 ng/mL and 0.058 ng/mL in cases and controls, respectively (P = 0.015). Low TT, low cFT and low BioT were correlated with hyperinflammatory syndrome (P = 0.018, P = 0.048 and P = 0.020, respectively) and associated with longer length of hospital stay (P = 0.052, P = 0.041 and P = 0.023, respectively). No association was found between sex hormone level and duration of viral shedding, or between sex hormone level and mortality rate. Conclusions A low level of testosterone was found to be a marker of clinical severity of COVID-19.
Marta Camici; Paolo Zuppi; Patrizia Lorenzini; Liliana Scarnecchia; Carmela Pinnetti; Stefania Cicalini; Emanuele Nicastri; Nicola Petrosillo; Fabrizio Palmieri; Gianpiero D’Offizi; Luisa Marchioni; Roberta Gagliardini; Roberto Baldelli; Vincenzo Schininà; Elisa Pianura; Federica Di Stefano; Stefano Curcio; Lucia Ciavarella; Giuseppe Ippolito; Enrico Girardi; Francesco Vaia; Andrea Antinori. Role of testosterone in SARS-CoV-2 infection: A key pathogenic factor and a biomarker for severe pneumonia. International Journal of Infectious Diseases 2021, 108, 244 -251.
AMA StyleMarta Camici, Paolo Zuppi, Patrizia Lorenzini, Liliana Scarnecchia, Carmela Pinnetti, Stefania Cicalini, Emanuele Nicastri, Nicola Petrosillo, Fabrizio Palmieri, Gianpiero D’Offizi, Luisa Marchioni, Roberta Gagliardini, Roberto Baldelli, Vincenzo Schininà, Elisa Pianura, Federica Di Stefano, Stefano Curcio, Lucia Ciavarella, Giuseppe Ippolito, Enrico Girardi, Francesco Vaia, Andrea Antinori. Role of testosterone in SARS-CoV-2 infection: A key pathogenic factor and a biomarker for severe pneumonia. International Journal of Infectious Diseases. 2021; 108 ():244-251.
Chicago/Turabian StyleMarta Camici; Paolo Zuppi; Patrizia Lorenzini; Liliana Scarnecchia; Carmela Pinnetti; Stefania Cicalini; Emanuele Nicastri; Nicola Petrosillo; Fabrizio Palmieri; Gianpiero D’Offizi; Luisa Marchioni; Roberta Gagliardini; Roberto Baldelli; Vincenzo Schininà; Elisa Pianura; Federica Di Stefano; Stefano Curcio; Lucia Ciavarella; Giuseppe Ippolito; Enrico Girardi; Francesco Vaia; Andrea Antinori. 2021. "Role of testosterone in SARS-CoV-2 infection: A key pathogenic factor and a biomarker for severe pneumonia." International Journal of Infectious Diseases 108, no. : 244-251.
Importance: Since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic, Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2) infection has been a serious challenge for immune-compromised patients with immune-mediated inflammatory diseases (IMIDs). Objective: Our aim was to investigate the impact of COVID-19 in terms of risks of infection, hospitalization and mortality in a cohort of patients with rheumatoid arthritis (RA), psoriasis (PSO) or inflammatory bowel disease (IBD). Furthermore, we studied the impact of SARS-CoV-2 infection on the prescribed drug regimen in these patients. Methods: Through the record linkage between health information systems, a cohort of patients, ≥18 years old, assisted in the Lazio region and who had suffered from immune-mediated inflammatory diseases (RA, PSO, IBD) between 2007 and 2019, was identified. The risk of infection, hospitalization or mortality for COVID-19, was assessed by logistic regression models, and reported in an Odds Ratio (ORs; CI 95%), adjusting for sex, age and the Charlson Comorbidity Index. We also estimated these risks separately by IMID and in the subgroup of prevalent biologic drug users. We investigated deferral of biological treatments in the study population by comparing the prevalence of weekly use of biologicals (2019–2020) before and during the pandemic periods. Findings: Within the 65,230 patients with IMIDs, the cumulative incidence for COVID-19 was 303/10,000 ab. In this cohort of patients, we observed a significantly higher risk of SARS-CoV-2 infection than the general population: OR = 1.17 (95% CI 1.12–1.22). The risk was higher even considering separately each disease and in the subgroup of prevalent biologic drug users. This last subgroup of patients showed a higher risk of death related to COVID-19 (OR 1.89; 95% CI 1.04–3.33) than the general population. However, no differences in terms of risks of hospitalization or death related to COVID-19 were recorded in patients with the IMIDs. Comparing the 2019–2020 prevalence of weekly biological drug treatments in prevalent biologic drug users, we found a decrease (−19.6%) during the lockdown, probably due to pandemic restrictions. Conclusions and Relevance: Patients with IMIDs seem to have a higher risk of SARS-CoV2 infection. However, other than for patients with prevalent biologic drug treatment, no significant differences in terms of hospitalization and mortality were reported compared to the general populations; further investigation is warranted on account of unmeasured confounding. In addition, during the lockdown period, the COVID-19 emergency highlighted a lower use of biologic drugs; this phenomenon requires strict pharmacological monitoring as it could be a proxy of forthcoming long-term clinical progression.
Valeria Belleudi; Alessandro Rosa; Francesca Poggi; Alessandro Armuzzi; Emanuele Nicastri; Delia Goletti; Andrea Diamanti; Marina Davoli; Nera Agabiti; Antonio Addis. Direct and Indirect Impact of COVID-19 for Patients with Immune-Mediated Inflammatory Diseases: A Retrospective Cohort Study. Journal of Clinical Medicine 2021, 10, 2388 .
AMA StyleValeria Belleudi, Alessandro Rosa, Francesca Poggi, Alessandro Armuzzi, Emanuele Nicastri, Delia Goletti, Andrea Diamanti, Marina Davoli, Nera Agabiti, Antonio Addis. Direct and Indirect Impact of COVID-19 for Patients with Immune-Mediated Inflammatory Diseases: A Retrospective Cohort Study. Journal of Clinical Medicine. 2021; 10 (11):2388.
Chicago/Turabian StyleValeria Belleudi; Alessandro Rosa; Francesca Poggi; Alessandro Armuzzi; Emanuele Nicastri; Delia Goletti; Andrea Diamanti; Marina Davoli; Nera Agabiti; Antonio Addis. 2021. "Direct and Indirect Impact of COVID-19 for Patients with Immune-Mediated Inflammatory Diseases: A Retrospective Cohort Study." Journal of Clinical Medicine 10, no. 11: 2388.
Prolonged B-cell depletion due to anti-CD20 monoclonal antibody (mAbs) therapy impairs the adaptive immune response, causing severe manifestations during COronaVIrus Disease-2019 (COVID-19). The cases of two patients under anti-CD20 therapy who experienced prolonged and severe COVID-19 successfully treated with mAbs against Severe Acute Respiratory Syndrome-CoV-2 spike proteins are reported.
Alessandra D’Abramo; Serena Vita; Gaetano Maffongelli; Andrea Mariano; Chiara Agrati; Concetta Castilletti; Delia Goletti; Giuseppe Ippolito; Emanuele Nicastri. Prolonged and severe SARS-CoV-2 infection in patients under B-cell-depleting drug successfully treated: A tailored approach. International Journal of Infectious Diseases 2021, 107, 247 -250.
AMA StyleAlessandra D’Abramo, Serena Vita, Gaetano Maffongelli, Andrea Mariano, Chiara Agrati, Concetta Castilletti, Delia Goletti, Giuseppe Ippolito, Emanuele Nicastri. Prolonged and severe SARS-CoV-2 infection in patients under B-cell-depleting drug successfully treated: A tailored approach. International Journal of Infectious Diseases. 2021; 107 ():247-250.
Chicago/Turabian StyleAlessandra D’Abramo; Serena Vita; Gaetano Maffongelli; Andrea Mariano; Chiara Agrati; Concetta Castilletti; Delia Goletti; Giuseppe Ippolito; Emanuele Nicastri. 2021. "Prolonged and severe SARS-CoV-2 infection in patients under B-cell-depleting drug successfully treated: A tailored approach." International Journal of Infectious Diseases 107, no. : 247-250.
SARS-CoV-2 serum neutralization assay represents the gold standard for assessing antibody-mediated protection in naturally infected and vaccinated individuals. In the present study, 662 serum samples collected from February 2020 to January 2021 from acute and convalescent COVID-19 patients were tested to determine neutralizing antibody (NAb) titers using a microneutralization test (MNT) for live SARS-CoV-2. Moreover, anti-SARS-CoV-2 IgG, IgA, and IgM directed against different viral antigens were measured by high-throughput automated platforms. We observed higher levels of NAbs in elderly (>60 years old) individuals and in patients presenting acute respiratory distress syndrome. SARS-CoV-2 NAbs develop as soon as five days from symptom onset and, despite a decline after the second month, persist for over 11 months, showing variable dynamics. Through correlation and receiver operating characteristic (ROC) curve analysis, we set up a testing algorithm, suitable for the laboratory workload, by establishing an optimal cutoff value of anti-SARS-CoV-2 IgG for convalescent plasma donors to exclude from MNT samples foreseen to have low/negative NAb titers and ineligible for plasma donation. Overall, MNT, although cumbersome and not suitable for routine testing of large sample sizes, remains the reference tool for the assessment of antibody-mediated immunity after SARS-CoV-2 infection. Smart testing algorithms may optimize the laboratory workflow to monitor antibody-mediated protection in COVID-19 patients, plasma donors, and vaccinated individuals.
Giulia Matusali; Francesca Colavita; Daniele Lapa; Silvia Meschi; Licia Bordi; Pierluca Piselli; Roberta Gagliardini; Angela Corpolongo; Emanuele Nicastri; Andrea Antinori; Giuseppe Ippolito; Maria Rosaria Capobianchi; Concetta Castilletti. SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus. Viruses 2021, 13, 655 .
AMA StyleGiulia Matusali, Francesca Colavita, Daniele Lapa, Silvia Meschi, Licia Bordi, Pierluca Piselli, Roberta Gagliardini, Angela Corpolongo, Emanuele Nicastri, Andrea Antinori, Giuseppe Ippolito, Maria Rosaria Capobianchi, Concetta Castilletti. SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus. Viruses. 2021; 13 (4):655.
Chicago/Turabian StyleGiulia Matusali; Francesca Colavita; Daniele Lapa; Silvia Meschi; Licia Bordi; Pierluca Piselli; Roberta Gagliardini; Angela Corpolongo; Emanuele Nicastri; Andrea Antinori; Giuseppe Ippolito; Maria Rosaria Capobianchi; Concetta Castilletti. 2021. "SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus." Viruses 13, no. 4: 655.
Since December 2019, SARS-CoV-2 infection has been still rapidly spreading, resulting in a pandemic, followed by an increasing number of cases in countries throughout the world. The severity of the disease depends on the patient’s overall medical condition but no appropriate markers are available to establish the prognosis of the patients. We performed a 16S rRNA gene sequencing, revealing an altered composition of the nasal/oropharyngeal (NOP) microbiota in 21 patients affected by COVID-19, paucisymptomatic or in an Intensive Care Unit (ICU), as compared to 10 controls negative for COVID-19 or eight affected by a different Human Coronavirus (HKU, NL63 and OC43). A significant decrease in Chao1 index was observed when patients affected by COVID-19 (in ICU) were compared to paucisymptomatic. Furthermore, patients who were in ICU, paucisymptomatic or affected by other Coronaviruses all displayed a decrease in the Chao1 index when compared to controls, while Shannon index significantly decreased only in patients under ICU as compared to controls and paucisymptomatic patients. At the phylum level, Deinococcus-Thermus was present only in controls as compared to SARS-CoV-2 patients admitted to ICU, paucisymptomatic or affected by other coronaviruses. Candidatus Saccharibacteria (formerly known as TM7) was strongly increased in negative controls and SARS-CoV-2 paucisymptomatic patients as compared to SARS-CoV-2 ICU patients. Other modifications were observed at a lower taxonomy level. Complete depletion of Bifidobacterium and Clostridium was exclusively observed in ICU SARS-CoV-2 patients, which was the only group characterized by the presence of Salmonella, Scardovia, Serratia and Pectobacteriaceae. In conclusion, our preliminary results showed that nasal/oropharyngeal microbiota profiles of patients affected with SARS-CoV-2 may provide valuable information in order to facilitate the stratification of patients and may open the way to new interventional strategies in order to ameliorate the outcome of the patients.
Martina Rueca; Andrea Fontana; Barbara Bartolini; Pierluca Piselli; Antonio Mazzarelli; Massimiliano Copetti; Elena Binda; Francesco Perri; Cesare Gruber; Emanuele Nicastri; Luisa Marchioni; Giuseppe Ippolito; Maria Capobianchi; Antonino Di Caro; Valerio Pazienza. Investigation of Nasal/Oropharyngeal Microbial Community of COVID-19 Patients by 16S rDNA Sequencing. International Journal of Environmental Research and Public Health 2021, 18, 2174 .
AMA StyleMartina Rueca, Andrea Fontana, Barbara Bartolini, Pierluca Piselli, Antonio Mazzarelli, Massimiliano Copetti, Elena Binda, Francesco Perri, Cesare Gruber, Emanuele Nicastri, Luisa Marchioni, Giuseppe Ippolito, Maria Capobianchi, Antonino Di Caro, Valerio Pazienza. Investigation of Nasal/Oropharyngeal Microbial Community of COVID-19 Patients by 16S rDNA Sequencing. International Journal of Environmental Research and Public Health. 2021; 18 (4):2174.
Chicago/Turabian StyleMartina Rueca; Andrea Fontana; Barbara Bartolini; Pierluca Piselli; Antonio Mazzarelli; Massimiliano Copetti; Elena Binda; Francesco Perri; Cesare Gruber; Emanuele Nicastri; Luisa Marchioni; Giuseppe Ippolito; Maria Capobianchi; Antonino Di Caro; Valerio Pazienza. 2021. "Investigation of Nasal/Oropharyngeal Microbial Community of COVID-19 Patients by 16S rDNA Sequencing." International Journal of Environmental Research and Public Health 18, no. 4: 2174.
Supplemental Digital Content is available in the text.
Franca del Nonno; Andrea Frustaci; Romina Verardo; Cristina Chimenti; Emanuele Nicastri; Andrea Antinori; Nicola Petrosillo; Eleonora Lalle; Chiara Agrati; Giuseppe Ippolito; and on behalf of the INMI COVID study group. Virus-Negative Myopericarditis in Human Coronavirus Infection. Circulation: Heart Failure 2020, 13, e007636 -e007636.
AMA StyleFranca del Nonno, Andrea Frustaci, Romina Verardo, Cristina Chimenti, Emanuele Nicastri, Andrea Antinori, Nicola Petrosillo, Eleonora Lalle, Chiara Agrati, Giuseppe Ippolito, and on behalf of the INMI COVID study group. Virus-Negative Myopericarditis in Human Coronavirus Infection. Circulation: Heart Failure. 2020; 13 (11):e007636-e007636.
Chicago/Turabian StyleFranca del Nonno; Andrea Frustaci; Romina Verardo; Cristina Chimenti; Emanuele Nicastri; Andrea Antinori; Nicola Petrosillo; Eleonora Lalle; Chiara Agrati; Giuseppe Ippolito; and on behalf of the INMI COVID study group. 2020. "Virus-Negative Myopericarditis in Human Coronavirus Infection." Circulation: Heart Failure 13, no. 11: e007636-e007636.
Background: RT-PCR on nasopharyngeal (NPS)/oropharyngeal swabs is the gold standard for diagnosis of SARS-CoV-2 infection and viral load monitoring. Oral fluid (OF) is an alternate clinical sample, easy and safer to collect and could be useful for COVID-19 diagnosis, monitoring viral load and shedding. Methods: Optimal assay conditions and analytical sensitivity were established for the commercial Simplexa™ COVID-19 Direct assay adapted to OF matrix. The assay was used to test 337 OF and NPS specimens collected in parallel from 164 hospitalized patients; 50 bronchoalveolar lavage (BAL) specimens from a subgroup of severe COVID-19 cases were also analysed. Results: Using Simplexa™ COVID-19 Direct on OF matrix, 100% analytical detection down to 1 TCID50/mL (corresponding to 4 × 103 copies (cp)/mL) was observed. No crossreaction with other viruses transmitted through the respiratory toute was observed. Parallel testing of 337 OF and NPS samples showed highly concordant results (κ = 0.831; 95 % CI = 0.771–0.891), and high correlation of Ct values (r = 0.921; p < 0.0001). High concordance and elevated correlation was observed also between OF and BAL. Prolonged viral RNA shedding was observed up to 100 days from symptoms onset (DSO), with 32% and 29% positivity observed in OF and NPS samples, respectively, collected between 60 and 100 DSO. Conclusions: Simplexa™ COVID-19 Direct assays on OF have high sensitivity and specificity to detect SARS-CoV-2 RNA and provide an alternative to NPS for diagnosis and monitoring SARS-CoV-2 shedding.
Licia Bordi; Giuseppe Sberna; Eleonora Lalle; Pierluca Piselli; Francesca Colavita; Emanuele Nicastri; Andrea Antinori; Evangelo Boumis; Nicola Petrosillo; Luisa Marchioni; Giulia Minnucci; Elena D’Agostini; Concetta Castilletti; Franco Locatelli; Alimuddin Zumla; Giuseppe Ippolito; Maria Capobianchi; on behalf of INMI ReCOVeRI Study Group. Frequency and Duration of SARS-CoV-2 Shedding in Oral Fluid Samples Assessed by a Modified Commercial Rapid Molecular Assay. Viruses 2020, 12, 1184 .
AMA StyleLicia Bordi, Giuseppe Sberna, Eleonora Lalle, Pierluca Piselli, Francesca Colavita, Emanuele Nicastri, Andrea Antinori, Evangelo Boumis, Nicola Petrosillo, Luisa Marchioni, Giulia Minnucci, Elena D’Agostini, Concetta Castilletti, Franco Locatelli, Alimuddin Zumla, Giuseppe Ippolito, Maria Capobianchi, on behalf of INMI ReCOVeRI Study Group. Frequency and Duration of SARS-CoV-2 Shedding in Oral Fluid Samples Assessed by a Modified Commercial Rapid Molecular Assay. Viruses. 2020; 12 (10):1184.
Chicago/Turabian StyleLicia Bordi; Giuseppe Sberna; Eleonora Lalle; Pierluca Piselli; Francesca Colavita; Emanuele Nicastri; Andrea Antinori; Evangelo Boumis; Nicola Petrosillo; Luisa Marchioni; Giulia Minnucci; Elena D’Agostini; Concetta Castilletti; Franco Locatelli; Alimuddin Zumla; Giuseppe Ippolito; Maria Capobianchi; on behalf of INMI ReCOVeRI Study Group. 2020. "Frequency and Duration of SARS-CoV-2 Shedding in Oral Fluid Samples Assessed by a Modified Commercial Rapid Molecular Assay." Viruses 12, no. 10: 1184.
Human monoclonal antibodies are safe, preventive and therapeutic tools, that can be rapidly developed to help restore the massive health and economic disruption caused by the Covid−19 pandemic. By single cell sorting 4277 SARS−CoV−2 spike protein specific memory B cells from 14 Covid−19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. Up to 65,9% of monoclonals neutralized the wild type virus at a concentration of >500 ng/mL, 23,6% neutralized the virus in the range of 100 − 500 ng/mL and 9,1% had a neutralization potency in the range of 10 − 100 ng/mL. Only 1,4% neutralized the authentic virus with a potency of 1−10 ng/mL. We found that the most potent neutralizing antibodies are extremely rare and recognize the RBD, followed in potency by antibodies that recognize the S1 domain, the S-protein trimeric structure and the S2 subunit. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS−CoV−2.
Emanuele Andreano; Emanuele Nicastri; Ida Paciello; Piero Pileri; Noemi Manganaro; Giulia Piccini; Alessandro Manenti; Elisa Pantano; Anna Kabanova; Marco Troisi; Fabiola Vacca; Dario Cardamone; Concetta De Santi; Linda Benincasa; Chiara Agrati; Maria Rosaria Capobianchi; Concetta Castilletti; Arianna Emiliozzi; Massimiliano Fabbiani; Francesca Montagnani; Lorenzo Depau; Jlenia Brunetti; Luisa Bracci; Emanuele Montomoli; Claudia Sala; Giuseppe Ippolito; Rino Rappuoli. Extremely potent human monoclonal antibodies from convalescent Covid-19 patients. 2020, 1 .
AMA StyleEmanuele Andreano, Emanuele Nicastri, Ida Paciello, Piero Pileri, Noemi Manganaro, Giulia Piccini, Alessandro Manenti, Elisa Pantano, Anna Kabanova, Marco Troisi, Fabiola Vacca, Dario Cardamone, Concetta De Santi, Linda Benincasa, Chiara Agrati, Maria Rosaria Capobianchi, Concetta Castilletti, Arianna Emiliozzi, Massimiliano Fabbiani, Francesca Montagnani, Lorenzo Depau, Jlenia Brunetti, Luisa Bracci, Emanuele Montomoli, Claudia Sala, Giuseppe Ippolito, Rino Rappuoli. Extremely potent human monoclonal antibodies from convalescent Covid-19 patients. . 2020; ():1.
Chicago/Turabian StyleEmanuele Andreano; Emanuele Nicastri; Ida Paciello; Piero Pileri; Noemi Manganaro; Giulia Piccini; Alessandro Manenti; Elisa Pantano; Anna Kabanova; Marco Troisi; Fabiola Vacca; Dario Cardamone; Concetta De Santi; Linda Benincasa; Chiara Agrati; Maria Rosaria Capobianchi; Concetta Castilletti; Arianna Emiliozzi; Massimiliano Fabbiani; Francesca Montagnani; Lorenzo Depau; Jlenia Brunetti; Luisa Bracci; Emanuele Montomoli; Claudia Sala; Giuseppe Ippolito; Rino Rappuoli. 2020. "Extremely potent human monoclonal antibodies from convalescent Covid-19 patients." , no. : 1.
The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti).
Francesco Vairo; Martin Aimè Coussoud-Mavoungou; Francine Ntoumi; Concetta Castilletti; Lambert Kitembo; Najmul Haider; Fabrizio Carletti; Francesca Colavita; Cesare Gruber; Marco Iannetta; Francesco Messina; Simone Lanini; Biez Ulrich Judicaël; Emanuela Giombini; Chiara Montaldo; Chantal Portella; Steve Diafouka-Diatela; Martina Rueca; Richard Kock; Barbara Bartolini; Leonard Mboera; Vincent Munster; Robert Fischer; Stephanie Seifert; César Muñoz-Fontela; Beatriz Escudero-Pérez; Sergio Gomez-Medina; Emily Nelson; Patrick Kjia Tungu; Emanuele Nicastri; Vincenzo Puro; Antonino Di Caro; Maria Capobianchi; Jacqueline Mikolo; Alimuddin Zumla; Giuseppe Ippolito; on behalf of the Pandora-ID-NET Consortium Chikungunya Outbreak Group Taskforce. Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation. Viruses 2020, 12, 1020 .
AMA StyleFrancesco Vairo, Martin Aimè Coussoud-Mavoungou, Francine Ntoumi, Concetta Castilletti, Lambert Kitembo, Najmul Haider, Fabrizio Carletti, Francesca Colavita, Cesare Gruber, Marco Iannetta, Francesco Messina, Simone Lanini, Biez Ulrich Judicaël, Emanuela Giombini, Chiara Montaldo, Chantal Portella, Steve Diafouka-Diatela, Martina Rueca, Richard Kock, Barbara Bartolini, Leonard Mboera, Vincent Munster, Robert Fischer, Stephanie Seifert, César Muñoz-Fontela, Beatriz Escudero-Pérez, Sergio Gomez-Medina, Emily Nelson, Patrick Kjia Tungu, Emanuele Nicastri, Vincenzo Puro, Antonino Di Caro, Maria Capobianchi, Jacqueline Mikolo, Alimuddin Zumla, Giuseppe Ippolito, on behalf of the Pandora-ID-NET Consortium Chikungunya Outbreak Group Taskforce. Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation. Viruses. 2020; 12 (9):1020.
Chicago/Turabian StyleFrancesco Vairo; Martin Aimè Coussoud-Mavoungou; Francine Ntoumi; Concetta Castilletti; Lambert Kitembo; Najmul Haider; Fabrizio Carletti; Francesca Colavita; Cesare Gruber; Marco Iannetta; Francesco Messina; Simone Lanini; Biez Ulrich Judicaël; Emanuela Giombini; Chiara Montaldo; Chantal Portella; Steve Diafouka-Diatela; Martina Rueca; Richard Kock; Barbara Bartolini; Leonard Mboera; Vincent Munster; Robert Fischer; Stephanie Seifert; César Muñoz-Fontela; Beatriz Escudero-Pérez; Sergio Gomez-Medina; Emily Nelson; Patrick Kjia Tungu; Emanuele Nicastri; Vincenzo Puro; Antonino Di Caro; Maria Capobianchi; Jacqueline Mikolo; Alimuddin Zumla; Giuseppe Ippolito; on behalf of the Pandora-ID-NET Consortium Chikungunya Outbreak Group Taskforce. 2020. "Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation." Viruses 12, no. 9: 1020.
As recently discussed in the Journal,1Cantini F. Niccoli L. Matarrese D. Nicastri E. Stobbione P. Goletti D Baricitinib therapy in COVID-19: a pilot study on safety and clinical impact.J Infect. 2020; (Apr 23Epub ahead of print])https://doi.org/10.1016/j.jinf.2020.04.017Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar baricitinib was safe and improved the clinical conditions in 12 patients with mild-moderate Coronavirus Disease 2019 (COVID-19) pneumonia. It is known that severe symptoms of COVID-19 may develop after a median of 8-days from illness-onset, with a median time to Intensive Care Unit (ICU) admission of 5 days from the dyspnea occurrence.2Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (6731) Google Scholar Currently, no antiviral therapies or vaccines are available. An uncontrolled immune response3Sun X. Wang T. Cai D. et al.Cytokine storm intervention in the early stages of COVID-19 pneumonia.Cytokine Growth Factor Rev. 2020; (Apr. 25)https://doi.org/10.1016/j.cytogfr.2020.04.002Crossref PubMed Scopus (34) Google Scholar is observed and is likely involved in tissues injury.4Adachi T. Chong J.M. Nakajima N. et al.Clinicopathological and immunohistochemical findings from autopsy of patient with COVID-19, Japan.Emerg Infect Dis. 2020; 26 (May 15[Epub ahead of print])https://doi.org/10.3201/eid2609.201353Crossref PubMed Scopus (14) Google Scholar Baricitinib is an anti-Janus kinase inhibitor-1 and −2, and has a dual action on COVID-19 therapy including the inhibition of cytokine release and SARS-CoV-2 endocytosis.5Stebbing J. Phelan A. Griffin I. Tucker C. Oechsle O. Richardson P COVID-19: combining antiviral and anti-inflammatory treatments.Lancet Infect Dis 2020. 2020; (Published online February 27https//doi.org/)https://doi.org/10.1016/51473-3099(20)30132-8Crossref Google Scholar Based on this evidence, we conducted an observational, retrospective, longitudinal multicenter-study in consecutive-hospitalized patients with COVID-19 moderate pneumonia to evaluate the 2-week effectiveness and safety of baricitinib combined with antivirals (lopinavir/ritonavir) compared with the standard of care therapy which was hydroxychloroquine and lopinavir/ritonavir. Primary aim was to evaluate the mortality rate; secondary aims were to evaluate the rate of ICU transfer, hospital discharge, improvement of respiratory parameters, adverse events (AEs) occurrence. Moreover, associations between therapy and modification of respiratory parameters and C-Reactive Protein (CRP), interleukin-6 (IL-6), lymphocyte percentage were evaluated.
Fabrizio Cantini; Laura Niccoli; Carlotta Nannini; Daniela Matarrese; Massimo Edoardo Di Natale; Pamela Lotti; Donatella Aquilini; Giancarlo Landini; Barbara Cimolato; Massimo Antonio Di Pietro; Michele Trezzi; Paolo Stobbione; Gabriele Frausini; Assunta Navarra; Emanuele Nicastri; Giovanni Sotgiu; Delia Goletti. Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study. Journal of Infection 2020, 81, 647 -679.
AMA StyleFabrizio Cantini, Laura Niccoli, Carlotta Nannini, Daniela Matarrese, Massimo Edoardo Di Natale, Pamela Lotti, Donatella Aquilini, Giancarlo Landini, Barbara Cimolato, Massimo Antonio Di Pietro, Michele Trezzi, Paolo Stobbione, Gabriele Frausini, Assunta Navarra, Emanuele Nicastri, Giovanni Sotgiu, Delia Goletti. Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study. Journal of Infection. 2020; 81 (4):647-679.
Chicago/Turabian StyleFabrizio Cantini; Laura Niccoli; Carlotta Nannini; Daniela Matarrese; Massimo Edoardo Di Natale; Pamela Lotti; Donatella Aquilini; Giancarlo Landini; Barbara Cimolato; Massimo Antonio Di Pietro; Michele Trezzi; Paolo Stobbione; Gabriele Frausini; Assunta Navarra; Emanuele Nicastri; Giovanni Sotgiu; Delia Goletti. 2020. "Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study." Journal of Infection 81, no. 4: 647-679.
Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)
Jonathan Grein; Norio Ohmagari; Daniel Shin; George Diaz; Erika Asperges; Antonella Castagna; Torsten Feldt; Gary Green; Margaret L. Green; Xavier Lescure; Emanuele Nicastri; Rentaro Oda; Kikuo Yo; Eugenia Quiros-Roldan; Alex Studemeister; John Redinski; Seema Ahmed; Jorge Bernett; Daniel Chelliah; Danny Chen; Shingo Chihara; Stuart H. Cohen; Jennifer Cunningham; Antonella D’Arminio Monforte; Saad Ismail; Hideaki Kato; Giuseppe Lapadula; Erwan L’Her; Toshitaka Maeno; Sumit Majumder; Marco Massari; Marta Mora-Rillo; Yoshikazu Mutoh; Duc Nguyen; Ewa Verweij; Alexander Zoufaly; Anu O. Osinusi; Adam DeZure; Yang Zhao; Lijie Zhong; Anand Chokkalingam; Emon Elboudwarej; Laura Telep; Leighann Timbs; Ilana Henne; Scott Sellers; Huyen Cao; Susanna K. Tan; Lucinda Winterbourne; Polly Desai; Robertino Mera; Anuj Gaggar; Robert P. Myers; Diana M. Brainard; Richard Childs; Timothy Flanigan. Compassionate Use of Remdesivir for Patients with Severe Covid-19. New England Journal of Medicine 2020, 382, 2327 -2336.
AMA StyleJonathan Grein, Norio Ohmagari, Daniel Shin, George Diaz, Erika Asperges, Antonella Castagna, Torsten Feldt, Gary Green, Margaret L. Green, Xavier Lescure, Emanuele Nicastri, Rentaro Oda, Kikuo Yo, Eugenia Quiros-Roldan, Alex Studemeister, John Redinski, Seema Ahmed, Jorge Bernett, Daniel Chelliah, Danny Chen, Shingo Chihara, Stuart H. Cohen, Jennifer Cunningham, Antonella D’Arminio Monforte, Saad Ismail, Hideaki Kato, Giuseppe Lapadula, Erwan L’Her, Toshitaka Maeno, Sumit Majumder, Marco Massari, Marta Mora-Rillo, Yoshikazu Mutoh, Duc Nguyen, Ewa Verweij, Alexander Zoufaly, Anu O. Osinusi, Adam DeZure, Yang Zhao, Lijie Zhong, Anand Chokkalingam, Emon Elboudwarej, Laura Telep, Leighann Timbs, Ilana Henne, Scott Sellers, Huyen Cao, Susanna K. Tan, Lucinda Winterbourne, Polly Desai, Robertino Mera, Anuj Gaggar, Robert P. Myers, Diana M. Brainard, Richard Childs, Timothy Flanigan. Compassionate Use of Remdesivir for Patients with Severe Covid-19. New England Journal of Medicine. 2020; 382 (24):2327-2336.
Chicago/Turabian StyleJonathan Grein; Norio Ohmagari; Daniel Shin; George Diaz; Erika Asperges; Antonella Castagna; Torsten Feldt; Gary Green; Margaret L. Green; Xavier Lescure; Emanuele Nicastri; Rentaro Oda; Kikuo Yo; Eugenia Quiros-Roldan; Alex Studemeister; John Redinski; Seema Ahmed; Jorge Bernett; Daniel Chelliah; Danny Chen; Shingo Chihara; Stuart H. Cohen; Jennifer Cunningham; Antonella D’Arminio Monforte; Saad Ismail; Hideaki Kato; Giuseppe Lapadula; Erwan L’Her; Toshitaka Maeno; Sumit Majumder; Marco Massari; Marta Mora-Rillo; Yoshikazu Mutoh; Duc Nguyen; Ewa Verweij; Alexander Zoufaly; Anu O. Osinusi; Adam DeZure; Yang Zhao; Lijie Zhong; Anand Chokkalingam; Emon Elboudwarej; Laura Telep; Leighann Timbs; Ilana Henne; Scott Sellers; Huyen Cao; Susanna K. Tan; Lucinda Winterbourne; Polly Desai; Robertino Mera; Anuj Gaggar; Robert P. Myers; Diana M. Brainard; Richard Childs; Timothy Flanigan. 2020. "Compassionate Use of Remdesivir for Patients with Severe Covid-19." New England Journal of Medicine 382, no. 24: 2327-2336.
Key pointsQuestionHow do nomograms and machine-learning algorithms of severity risk prediction and triage of COVID-19 patients at hospital admission perform?FindingsThis model was prospectively validated on six test datasets comprising of 426 patients and yielded AUCs ranging from 0.816 to 0.976, accuracies ranging from 70.8% to 93.8%, sensitivities ranging from 83.7% to 100%, and specificities ranging from 41.0% to 95.7%. The cut-off probability values for low, medium, and high-risk groups were 0.072 and 0.244.MeaningThe findings of this study suggest that our models performs well for the diagnosis and prediction of progression to severe or critical illness of COVID-19 patients and could be used for triage of COVID-19 patients at hospital admission.IMPORTANCEThe outbreak of the coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality for severely and critically ill patients. However, the availability of validated nomograms and the machine-learning model to predict severity risk and triage of affected patients is limited.OBJECTIVETo develop and validate nomograms and machine-learning models for severity risk assessment and triage for COVID-19 patients at hospital admission.DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort of 299 consecutively hospitalized COVID-19 patients at The Central Hospital of Wuhan, China, from December 23, 2019, to February 13, 2020, was used to train and validate the models. Six cohorts with 426 patients from eight centers in China, Italy, and Belgium, from February 20, 2020, to March 21, 2020, were used to prospectively validate the models.MAIN OUTCOME AND MEASURESThe main outcome was the onset of severe or critical illness during hospitalization. Model performances were quantified using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity.RESULTSOf the 299 hospitalized COVID-19 patients in the retrospective cohort, the median age was 50 years ((interquartile range, 35.5-63.0; range, 20–94 years) and 137 (45.8%) were men. Of the 426 hospitalized COVID-19 patients in the prospective cohorts, the median age was 62.0 years ((interquartile range, 50.0-72.0; range, 19-94 years) and 236 (55.4%) were men. The model was prospectively validated on six cohorts yielding AUCs ranging from 0.816 to 0.976, with accuracies ranging from 70.8% to 93.8%, sensitivities ranging from 83.7% to 100%, and specificities ranging from 41.0% to 95.7%. The cut-off values of the low, medium, and high-risk probabilities were 0.072 and 0.244. The developed online calculators can be found at https://covid19risk.ai/.CONCLUSION AND RELEVANCEThe machine learning models, nomograms, and online calculators might be useful for the prediction of onset of severe and critical illness among COVID-19 patients and triage at hospital admission. Further prospective research and clinical feedback are necessary to evaluate the clinical usefulness of this model and to determine whether these models can help optimize medical resources and reduce mortality rates compared with current clinical practices.
Guangyao Wu; Pei Yang; Henry C. Woodruff; Xiangang Rao; Julien Guiot; Anne-Noelle Frix; Michel Moutschen; Renaud Louis; Jiawei Li; Jing Li; Chenggong Yan; Dan Du; Shengchao Zhao; Yi Ding; Bin Liu; Wenwu Sun; Fabrizio Albarello; Alessandra D’Abramo; Vincenzo Schininà; Emanuele Nicastri; Mariaelena Occhipinti; Giovanni Barisione; Emanuela Barisione; Iva Halilaj; Yuanliang Xie; Xiang Wang; Pierre Lovinfosse; Jianlin Wu; Philippe Lambin. Development of a Clinical Decision Support System for Severity Risk Prediction and Triage of COVID-19 Patients at Hospital Admission: an International Multicenter Study. 2020, 1 .
AMA StyleGuangyao Wu, Pei Yang, Henry C. Woodruff, Xiangang Rao, Julien Guiot, Anne-Noelle Frix, Michel Moutschen, Renaud Louis, Jiawei Li, Jing Li, Chenggong Yan, Dan Du, Shengchao Zhao, Yi Ding, Bin Liu, Wenwu Sun, Fabrizio Albarello, Alessandra D’Abramo, Vincenzo Schininà, Emanuele Nicastri, Mariaelena Occhipinti, Giovanni Barisione, Emanuela Barisione, Iva Halilaj, Yuanliang Xie, Xiang Wang, Pierre Lovinfosse, Jianlin Wu, Philippe Lambin. Development of a Clinical Decision Support System for Severity Risk Prediction and Triage of COVID-19 Patients at Hospital Admission: an International Multicenter Study. . 2020; ():1.
Chicago/Turabian StyleGuangyao Wu; Pei Yang; Henry C. Woodruff; Xiangang Rao; Julien Guiot; Anne-Noelle Frix; Michel Moutschen; Renaud Louis; Jiawei Li; Jing Li; Chenggong Yan; Dan Du; Shengchao Zhao; Yi Ding; Bin Liu; Wenwu Sun; Fabrizio Albarello; Alessandra D’Abramo; Vincenzo Schininà; Emanuele Nicastri; Mariaelena Occhipinti; Giovanni Barisione; Emanuela Barisione; Iva Halilaj; Yuanliang Xie; Xiang Wang; Pierre Lovinfosse; Jianlin Wu; Philippe Lambin. 2020. "Development of a Clinical Decision Support System for Severity Risk Prediction and Triage of COVID-19 Patients at Hospital Admission: an International Multicenter Study." , no. : 1.
As discussed in the Journal recently1Li R. Qiao S. Zhang G Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV.J Infect. Apr 2020; 80: 469-496Scopus (24) Google Scholar the SARS-CoV-2, a new β-Coronavirus, uses the Angiotensin Converting Enzyme-2 Receptor to enter airway cells. Viral endocytosis is mediated by several factors, including clathrin, the adaptor protein-2 complex (AP2) and the adaptor-associated kinase-1 (AAK1).2Conner S.D. Schmid S.L Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis.J Cell Biol. 2002; 156: 921-929Crossref PubMed Scopus (186) Google Scholar
Fabrizio Cantini; Laura Niccoli; Daniela Matarrese; Emanuele Nicastri; Paolo Stobbione; Delia Goletti. Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact. Journal of Infection 2020, 81, 318 -356.
AMA StyleFabrizio Cantini, Laura Niccoli, Daniela Matarrese, Emanuele Nicastri, Paolo Stobbione, Delia Goletti. Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact. Journal of Infection. 2020; 81 (2):318-356.
Chicago/Turabian StyleFabrizio Cantini; Laura Niccoli; Daniela Matarrese; Emanuele Nicastri; Paolo Stobbione; Delia Goletti. 2020. "Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact." Journal of Infection 81, no. 2: 318-356.
Filoviruses have become a worldwide public health concern, especially during the 2013-2016 Western Africa Ebola virus disease (EVD) outbreak-the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. EVD is associated with pathologies in several organs, including the liver, kidney, and lung. During the 2013-2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, little is known about lung pathogenesis and the controversial issue of aerosol transmission in EVD. This review highlights the pulmonary involvement in EVD, with a special focus on the new data emerging from the 2013-2016 Ebola outbreak.
Eleonora Lalle; Mirella Biava; Emanuele Nicastri; Francesca Colavita; Antonino Di Caro; Francesco Vairo; Simone Lanini; Concetta Castilletti; Martin Langer; Alimuddin Zumla; Gary Kobinger; Maria R. Capobianchi; Giuseppe Ippolito. Pulmonary Involvement during the Ebola Virus Disease. Viruses 2019, 11, 780 .
AMA StyleEleonora Lalle, Mirella Biava, Emanuele Nicastri, Francesca Colavita, Antonino Di Caro, Francesco Vairo, Simone Lanini, Concetta Castilletti, Martin Langer, Alimuddin Zumla, Gary Kobinger, Maria R. Capobianchi, Giuseppe Ippolito. Pulmonary Involvement during the Ebola Virus Disease. Viruses. 2019; 11 (9):780.
Chicago/Turabian StyleEleonora Lalle; Mirella Biava; Emanuele Nicastri; Francesca Colavita; Antonino Di Caro; Francesco Vairo; Simone Lanini; Concetta Castilletti; Martin Langer; Alimuddin Zumla; Gary Kobinger; Maria R. Capobianchi; Giuseppe Ippolito. 2019. "Pulmonary Involvement during the Ebola Virus Disease." Viruses 11, no. 9: 780.
On September 7, 2017, three potentially autochthonous cases of chikungunya were notified in the Lazio region. An Outbreak investigation based on established surveillance system data and molecular analysis of viral variant(s) were conducted. Epidemiological analysis suggested the occurrence of 3 main foci of local transmission. The major focus involved 317 cases with epidemiological link with the area of Anzio. The other two foci occurred in Rome (80 cases) and Latina (8 cases). Cumulative incidence in Anzio and Latina were 331.4 and 7.13 per 100,000 residents, respectively. Cumulative incidences ranged from 1.4 to 14.3/100,000 residents in Rome. This is the first report of a chikungunya outbreak involving a densely populated urban area in a western country. The outbreak probably started in Anzio, spread by continuity to neighbouring villages, and then to the metropolitan area of Rome and to the Latina area favoured by the touristic nature of the Anzio area.
Francesco Vairo; Alessia Mammone; Simone Lanini; Emanuele Nicastri; Concetta Castilletti; Fabrizio Carletti; Vincenzo Puro; Domenico Di Lallo; Vincenzo Panella; Donatella Varrenti; Paola Scaramozzino; Antonino Di Caro; Paola Scognamiglio; Maria Rosaria Capobianchi; Giuseppe Ippolito; Chikungunya Lazio Outbreak Group. Local transmission of chikungunya in Rome and the Lazio region, Italy. PLOS ONE 2018, 13, e0208896 .
AMA StyleFrancesco Vairo, Alessia Mammone, Simone Lanini, Emanuele Nicastri, Concetta Castilletti, Fabrizio Carletti, Vincenzo Puro, Domenico Di Lallo, Vincenzo Panella, Donatella Varrenti, Paola Scaramozzino, Antonino Di Caro, Paola Scognamiglio, Maria Rosaria Capobianchi, Giuseppe Ippolito, Chikungunya Lazio Outbreak Group. Local transmission of chikungunya in Rome and the Lazio region, Italy. PLOS ONE. 2018; 13 (12):e0208896.
Chicago/Turabian StyleFrancesco Vairo; Alessia Mammone; Simone Lanini; Emanuele Nicastri; Concetta Castilletti; Fabrizio Carletti; Vincenzo Puro; Domenico Di Lallo; Vincenzo Panella; Donatella Varrenti; Paola Scaramozzino; Antonino Di Caro; Paola Scognamiglio; Maria Rosaria Capobianchi; Giuseppe Ippolito; Chikungunya Lazio Outbreak Group. 2018. "Local transmission of chikungunya in Rome and the Lazio region, Italy." PLOS ONE 13, no. 12: e0208896.