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Introduction: The clinical progression of severe coronavirus disease 2019 (COVID-19) is associated with uncontrolled activation of inflammatory cytokines that results in excessive tissue injury, among which is interleukin-8 (IL-8). Aim(s): To assess the efficacy and safety of reparixin, an inhibitor of IL-8 receptors, as add-on therapy to the standard of care for severe COVID-19 pneumonia. Method(s): This was a Phase 3, multicenter, randomized, placebo-controlled study in hospitalized adult patients with COVID-19 requiring oxygen support and/or noninvasive ventilation. From February to July 2021, patients were randomized 2:1 to oral reparixin or placebo in addition to the standard of care for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure. This study was funded by Dompe Farmaceutici SpA (ClinicalTrials.gov: NCT04878055). Result(s): Of the 278 randomized patients, 185 patients in the reparixin group and 94 patients in the placebo group were included in the primary intention-to-treat analysis. The proportion of patients alive and free of respiratory failure at day 28 was greater in the reparixin group but not statistically significant (n=152 (89.4%) vs. n=71 (85.5%), OR: 1.63, 95% CI: 0.75 - 3.51, p= 0.2). While time to recovery was not different between groups, patients who received reparixin had a lower intensive care unit admission rate. Reparixin was well-tolerated. Conclusion(s): This trial did not meet the primary efficacy endpoint due to the low mortality in both arms, yet reparixin showed a promising trend towards limiting disease progression. A confirmatory Phase 3 study is currently underway.
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Background: To validate an innovative eradication model for HCV infection in undocumented migrants and low-income refugees living Southern Italy. Method(s): a prospective, multicenter, collaborative study was started in June 2018 with The study was stopped in February 2020 due to the outbreak of SARS-CoV- 2 infection in Italy and was resumed in February 2021 until November 2021. At the six 1st level centers participating to the study volunteer associations that deal with the first needs of disadvantaged people performed the enrolment and the screening for anti-HCV, HBsAg and anti-HIV;epidemiological data were collected in an electronic database. Anti-HCV- positive subjects were sent to two 3rd level centers for the clinical, virological and therapeutic evaluation. For the HCV-RNA- positive subjects HCV genotyping and a clinical, biochemical and ultrasound staging was performed. The HCV RNA-positive subjects have been treated with sofosbuvir-velpatasvir for 12 weeks and followed for 12 months from the end of therapy Results: Of the 3,991 migrants observed in the study period, 3,897 (97.6%) accepted to be screened. They were young (median age 26 years), predominantly male (85.9%) and came from North Africa (3.8%), from Sub-Saharan Africa (68.4%), from Eastern Europe (8.1%), from Indo-Pakistan (17%) and from other countries (2.7%). Of the 3,897 enrolled subjects, 185 (4.7%) resulted anti-HCV positive. The Figure shows the HCV-cure cascade. All the 185 anti-HCV- positive subjects were linked to care at 3rdID and tested for HCV RNA and 53 (28.6%) resulted HCV-RNA positive. Of these, 48 (90.6%) started DAA regimen with sofosbuvir plus velpatasvir (16 with GT 1b, 11 with 1a, 16 with 3, 3 with 4 and 2 with 2). Of these 48 subjects, 47 (97.9%) showed a SVR12 and SVR 24, and one dropped-out in follow-up after the stop of DAA treatment. No subject had adverse event. Conclusion(s): This model seems to be effective to eradicate HCV infection among a difficult-to- manage population, such as undocumented migrants and low-income refugees. (Figure Presented).
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Introduction: SARS-Co-V2 neuroinvasive ability might be the basis for the onset of delirium and neuropsychiatric outcomes. Objective(s): We hypothesized that some infected patients with preexisting cognitive dysfunction may present delirium as unique manifestation of COVID-19 infection or as a prodrome of a new episode consistent with the psychiatric history. Method(s): We conducted a PubMed literature search to verify whether cognitive impairment might predispose to COVID-19. We included three patients with mild cognitive impairment and delirium at admission for SARS-Co-V2 suspected infection. Delirium was diagnosed according to DSM-5 criteria, Cognitive Assessment Method and Coma Glasgow Scale. Result(s): Literature analysis evidenced patients presenting delirium or delirium-like symptoms as clinical manifestation of COVID-19, plus a cognitive impairment, from mild to severe, which preexisted or was evidenced during the acute phase or after the infection. Most studies described delirium in patients with a past neurological/ psychiatric history. Contrasting data emerged on the potential link between COVID-19 and delirium in patients with cognitive impairment and without a past neuropsychiatric history. Our patients had no history of other medical complications. Our first patient had no psychiatric history, the second reported only a depressive episode, and the third had story of bipolar disorder. Delirium resolved completely after 2 days in the first patient. The other patients required 4 and 14 days to resolve: delirium appeared as the prodrome of a new psychiatric episode in line with their past history. Conclusion(s): Clinicians should acknowledge the possibility that COVID-19 infection may appear as delirium and acute psychiatric sequelae as unique manifestation.
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Introduction: Patients with Multiple Sclerosis (pwMS) treated with Ocrelizumab (OCR) and Fingolimod (FNG) have shown a blunted humoral response to the first two doses of the BNT162b2 mRNA Covid-19 vaccine. The assessment of the safety and the humoral response to a third booster dose of the same vaccine is therefore relevant within this population. Aim(s): To investigate the safety and the humoral response to a third booster dose of the BNT162b2 mRNA Covid-19 vaccine in pwMS on OCR/FNG, comparing it with age- and sex-matched healthy controls (HCs). Method(s): Serum samples were collected from HCs and pwMS treated with OCR or FNG at the following scheduled time points: before the first of two vaccine doses (T0);8 (T1), 16 (T2), 24 (T3) weeks after the first dose;within 8 weeks before (T0b) and after (T1b) the booster dose. IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) were quantified and expressed as binding antibody units (BAU)/mL. Result(s): 40 HCs and 47 pwMS (28 on OCR and 19 on FNG) were included in the study. All (100%) HCs mounted a positive (>33.8 BAU/mL) humoral response at T1 and preserved it until (T2-T3- T0b) and after (T1b) the third booster dose. At T0b only 12 (42.9%) pwMS on OCR and 6 (31.6%) on FNG were positive while, at T1b 16 (57.14%) pwMS on OCR and 16 (84.2%) on FNG, passed the threshold of positivity. Anti-TSP IgG titers in HCs were significantly higher than those of pwMS on OCR and on FNG at all time points, while no differences were found at all time points between pwMS on OCR and those on FNG. HCs showed a significant higher (relative) increase of Anti-TSP IgG levels at T1b with respect to OCR (p<.001) and FNG (p=.032) groups. The increase of Anti-TSP IgG levels in the pwMS on FNG was significantly higher than those in the OCR group (p<.001). No socio-demographic, clinical, or laboratory variables were able to predict the increase of anti-TSP IgG levels between T0b and T1b. Neither clinical relapses nor severe adverse events were reported in pwMS after each of the three doses of vaccine during the follow- up period. Conclusion(s): The administration of a third booster dose of BNT162b2 mRNA Covid-19 vaccine to OCR- and FNG-treated pwMS is able to revive the humoral response, independently of any demographic, clinical or laboratory variable, and confirms a good safety and tolerability profile, not only in terms of adverse events but also in terms of MS relapses.
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Background and aims: To validate an innovative eradication model for HCV infection in undocumented migrants and low-income refugees living Southern Italy. Method: a prospective, multicenter, collaborative study was started in June 2018 with The studywas stopped in February 2020 due to the outbreak of SARS-CoV-2 infection in Italy and was resumed in February 2021. At the six 1st level centers participating to the study volunteer associations that deal with the first needs of disadvantaged people performed the enrolment and the screening for anti-HCV, HBsAg and anti-HIV;epidemiological data were collected in an electronic database. Anti-HCV-positive subjects were sent to two 3rd level centers for the clinical, virological and therapeutic evaluation. For the HCV-RNA-positive subjects HCV genotyping and a clinical, biochemical and ultrasound staging was performed. The HCV RNApositive subjects have been treated with sofosbuvir-velpatasvir for 12 weeks and followed for 12 months from the end of therapy. Results: Of the 3, 991 migrants observed in the study period, 3, 897 (97.6%) accepted to be screened. They were young (median age 26 years), predominantly male (85.9%) and came from North Africa (3.8%), from Sub-Saharan Africa (68.4%), from Eastern Europe (8.1%), from Indo-Pakistan (17%) and from other countries (2.7%). Of the 3, 897 enrolled subjects, 185 (4.7%) resulted anti-HCV positive. The Figure shows the HCV-cure cascade. All the 185 anti-HCV-positive subjects were linked to care at 3rdID and tested for HCV RNA and 53 (28.6%) resulted HCV-RNA positive. Of these, 46 (86.8%) started DAA regimen with sofosbuvir plus velpatasvir (15 with GT 1b, 10 with 1a, 16 with 3, 3 with 4 and 2 with 2). Forty-two completed the follow-up and 4 was still pending. Of these 42 subjects, 41 (97.6%) showed a SVR12 and SVR 24, and one dropped-out in follow-up after the stop of DAA treatment. No subject had adverse event. (Figure Presented) Conclusion: This model seems to be effective to eradicate HCV infection among a difficult-to-manage population, such as undocumented migrants and low-income refugees
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The COVID-19 pandemic has emphasized the need for portable, small-size, low-cost, simple to use, and highly sensitive sensors able to measure a specific substance, with the capability of the transmission over the Internet of statistical data, such as in this specific case on the spread of the SARS-CoV-2 virions. Moreover, to resolve the COVID-19 emergency, the possibility of making selective SARS-CoV-2 measurements in different aqueous matrices could be advantageous. Thus, the realization of rapid and innovative point-of-care diagnostics tests has become a global priority. In response to the current need for quick, highly sensitive and on-site detection of the SARS-CoV-2 virions in different aqueous solutions, two different nanolayer biorecognition systems separately combined with an adaptable optical fiber sensor have been reported in this work. More specifically, two SARS-CoV-2 sensors have been developed and tested by exploiting a plasmonic plastic optical fiber (POF) sensor coupled with two different receptors, both designed for the specific recognition of the SARS-CoV-2 Spike protein;one is aptamer-based and the other one Molecular Imprinted Polymer-based. The preliminary tests on SARS-CoV-2 virions, performed on samples of nasopharyngeal (NP) swabs in universal transport medium (UTM), were compared with data obtained using reverse-transcription polymerase chain reaction (RT-PCR). According to these preliminary experimental results obtained exploiting both receptors, the sensitivity of the proposed SARS-CoV-2 optical fiber sensors proved to be high enough to detect virions. Furthermore, a relatively fast response time (a few minutes) to detect virions was obtained without additional reagents, with the capability to transmit the data via the Internet automatically. © 2021 The Authors
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Introduction: Since the worldwide launch of the SARS-CoV-2 vaccine campaign, there have been many uncertainties regarding the immune response to vaccination in patients with multiple sclerosis (pwMS), particularly those on high efficacy disease-modifying therapies (DMTs). Aim: To evaluate humoral response to NT162b2-mRNACovid- 19 vaccine in pwMS on high efficacy DMTs compared to healthy controls (HCs). Methods: We collected serum samples before the first dose and 7 days after the second dose of the NT162b2-mRNA-Covid-19 vaccine from 54 HCs and 93 pwMS on high efficacy DMTs (Ocrelizumab/OCR, Fingolimod/FNG, Natalizumab/NTZ). Exclusion criteria: history of Covid-19, baseline positive SARSCoV- 2 IgG antibodies, steroids administration within the month prior to the first dose of vaccine. Sera were tested using the LIAISONRSARS-CoV-2 TrimericSIgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The IgG-titers were expressed in Binding Antibody Units (BAU) with 33.8 BAU/mL as cut-off. Results: Sera of 51 HCs and 80pwMS (31 OCR, 25 FNG, 24 NTZ) were analyzed, while 3 HCs and 13 pwMS (4OCR, 5FNG, 4NTZ) were kept out due to exclusion criteria. Age, sex, and disease duration were similar across groups. Seven days after the second dose of the vaccine, SARS-CoV-2 IgG antibodies were detected in all HCs and pwMS on NTZ, in 17(54.8%) pwMS on OCR and 10(40%) pwMS on FNG. pwMS on OCR (median 59.8 BAU/mL;P25-75 4.81-598) and FNG (median 21.5;P25-75 7.49-116) showed a significant blunted response (p<0.0001, both) when compared with HCs (median 1860;P25-75 1180-4865) and NTZ patients (p<0.0001, both). pwMS on NTZ mounted a humoral response (median 3015;P25-75 1495-4905) similar to HCs (p=0.52). Interestingly, we observed a positive association between humoral response and time elapsed since the last OCR infusion (rho 0.46,p=0.001) and an inverse correlation between humoral response and treatment duration in pwMS on FTY (rho -0.57,p=0.004). No correlation was found with CD20 levels in the OCR group. Discussion: We found a clear blunted humoral response to NT162b2-mRNA-Covid-19 vaccine in pwMS treated with OCR and FNG, with a significant relationship with treatment duration in FNG-treated pwMS and time elapsed since the last infusion in the OCR-treated pwMS. Contrariwise, we found an efficient humoral response in NTZ-treated pwMS. Further data are needed to inform which strategy could optimize the response to vaccines in pwMS on OCR and FTY.
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In a time, where first solid oxide based systems enter demonstration and commercial markets, the European NewSOC project focuses on next generations. It aims at significantly improving performance, durability, and cost competitiveness of solid oxide cells and stacks compared to state-of-the-art (SoA). In order to achieve these goals, NewSOC investigates twelve innovative concepts in the following areas: (i) structural optimization and innovative architectures based on SoA materials, (ii) alternative materials, which allow for overcoming inherent challenges of SoA, (iii) innovative manufacturing to reduce critical raw materials and reduction of environmental footprint at improved performance and lifetime. The NewSOC unifies competences of 16 strong research and industry players. First scientific highlights were achieved despite the challenging working conditions under the European wide Covid-19 restrictions in the first year of the project. The presentation will provide a selection of these highlights. © 2021 Electrochemical Society Inc.. All rights reserved.
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Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.