• Fast and accurate genome-wide predictions and structural modeling of protein-protein interactions using Galaxy

      Institute for Genomics and Evolutionary Medicine (iGEM) (Temple University) (2021-04-14)
      Protein-protein interactions play a crucial role in almost all cellular processes. Identifying interacting proteins reveals insight into living organisms and yields novel drug targets for disease treatment. Here, we present a publicly available, automated pipeline to predict genome-wide protein-protein interactions and produce high-quality multimeric structural models. Application of our method to the Human and Yeast genomes yield protein-protein interaction networks similar in quality to common experimental methods. We identified and modeled Human proteins likely to interact with the papain-like protease of SARS-CoV2’s non-structural protein 3 (Nsp3). We also produced models of SARS-CoV2’s spike protein (S) interacting with myelin-oligodendrocyte glycoprotein receptor (MOG) and dipeptidyl peptidase-4 (DPP4). The presented method is capable of confidently identifying interactions while providing high-quality multimeric structural models for experimental validation. The interactome modeling pipeline is available at usegalaxy.org and usegalaxy.eu.
    • First-in-Human Trial of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine with Adjuvant of Aluminum Hydroxide and CpG 1018

      Hsieh, Szu-Min; Liu, Wang-Da; Huang, Yu-Shan; Lin, Yi-Jiun; Hsieh, Erh-Fang; Lian, Wei-Cheng; Chen, Charles; Tai, I-Chen; Chang, Shan-Chwen (2021-04-06)
      Design: This is a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a recombinant stabilized prefusion SARS-CoV-2 spike (S-2P) protein vaccine with adjuvant of aluminum hydroxide and CpG 1018. Methods: We enrolled 45 healthy adults from 20 to 49 years of age to be administered with two vaccinations of MVC-COV1901 in a low dose (LD), middle dose (MD), and high dose (HD) of spike protein at 28 days apart. There were 15 participants in each dose group, and all of them were followed up for 28 days after the second vaccination at the time of interim analysis. Adverse events (AEs) and laboratory data were recorded for safety evaluation. Blood samples were collected for wild-type SARS-CoV-2 and pseudovirus neutralization assays as well as SARS-CoV-2 spike-specific immunoglobulin G (IgG) at various times. Overall, the study duration will be 7 months. Results: Solicited events were mostly mild and similar in the participants of all three dose groups. No subject experienced fever. There were no serious nor adverse events of special interest at the time point of this interim report. After the second vaccination, the SARS-CoV-2 spike specific IgG titers increased with peak geometric mean titers at 7178.245 (LD), 7746.086 (MD), and 11220.58 (HD), respectively. Serum neutralizing activity was detected by two methods in all participants of MD and HD groups, with geometric mean values generally comparable to those of a panel of control convalescent serum specimens. All of the participants in the MD and HD groups were seroconverted after the second vaccination. Conclusions: The MVC-COV1901 vaccine is safe and elicits remarkable immune responses especially in the MD and HD groups.
    • Fondaparinux: Should It Be Studied in Patients with COVID-19 Disease?

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-10-01)
      We have read with interest the review article by Bikdeli et al recently published in Thrombosis and Haemostasis on the priority in planning studies on the different anticoagulants in coronavirus disease 2019 (COVID-19) infection.[1] The authors describe the characteristics of both the anticoagulants available today and in the future. Antiplatelets drugs have been also considered. Surprisingly, fondaparinux (FPX) has reached a lower priority research mean (4.89) than unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) at intermediate (7.82) or therapeutic (7.53) dosage for hospitalized ward and intensive care unit patients. We believe that properties of these drugs have been overlooked by the scientific panel of the Global COVID-19 Thrombosis Collaborative Group.
    • Freely accessible ready to use global infrastructure for SARS-CoV-2 monitoring

      Maier, Wolfgang; Bray, Simon; van den Beek, Marius; Bouvier, Dave; Coraor, Nathaniel; Miladi, Milad; Singh, Babita; Rambla De Argila, Jordi; Baker, Dannon; Roach, Nathan; Gladman, Simon; Coppens, Frederik; Martin, Darren P.; Lonie, Andrew; Grüning, Björn; Pond, Sergei; Nekrutenko, Anton; Pond|0000-0003-4817-4029 (2021-03-25)
      The COVID-19 pandemic is the first global health crisis to occur in the age of big genomic data. Although data generation capacity is well established and sufficiently standardized, analytical capacity is not. To establish analytical capacity it is necessary to pull together global computational resources and deliver the best open source tools and analysis workflows within a ready to use, universally accessible resource. Such a resource should not be controlled by a single research group, institution, or country. Instead it should be maintained by a community of users and developers who ensure that the system remains operational and populated with current tools. A community is also essential for facilitating the types of discourse needed to establish best analytical practices. Bringing together public computational research infrastructure from the USA, Europe, and Australia, we developed a distributed data analysis platform that accomplishes these goals. It is immediately accessible to anyone in the world and is designed for the analysis of rapidly growing collections of deep sequencing datasets. We demonstrate its utility by detecting allelic variants in high-quality existing SARS-CoV-2 sequencing datasets and by continuous reanalysis of COG-UK data. All workflows, data, and documentation is available at https://covid19.galaxyproject.org.
    • From examining the relationship between (corona)viral adhesins and galectins to glyco-perspectives

      Institute of Computational Molecular Science (Temple University) (2021-03-16)
      Glycan-lectin recognition is vital to processes that impact human health, including viral infections. Proceeding from crystallographical evidence of case studies on adeno-, corona-, and rotaviral spike proteins, the relationship of these adhesins to mammalian galectins was examined by computational similarity assessments. Intrafamily diversity among human galectins was in the range of that to these viral surface proteins. Our findings are offered to inspire the consideration of lectin-based approaches to thwart infection by present and future viral threats, also mentioning possible implications for vaccine development.
    • From loss to recovery: how to effectively assess chemosensory impairments during COVID-19 pandemic

      Cecchetto, Cinzia; Di Pizio, Antonella; Genovese, Federica; Calcinoni, Orietta; Macchi, Alberto; Dunkel, Andreas; Ohla, Kathrin; Spinelli, Sara; Farruggia, Michael C.; Joseph, Paule V.; Menini, Anna; Cantone, Elena; Dinnella, Caterina; Cecchini, Maria Paola; D’Errico, Anna; Mucignat-Caretta, Carla; Parma, Valentina; Dibattista, Michele; Parma|0000-0003-0276-7072 (2021-03-26)
      Chemosensory impairments have been established as a specific indicator of COVID-19. They affect most patients and may persist long past the resolution of respiratory symptoms, representing an unprecedented medical challenge. Since the SARS-CoV-2 pandemic started, we now know much more about smell, taste, and chemesthesis loss associated with COVID-19. However, the temporal dynamics and characteristics of recovery are still unknown. Here, capitalizing on data from the Global Consortium for Chemosensory Research (GCCR) crowdsourced survey, we assessed chemosensory abilities after the resolution of respiratory symptoms in participants diagnosed with COVID-19 during the first wave of the pandemic in Italy. This analysis led to the identification of two patterns of chemosensory recovery, limited (partial) and substantial, which were found to be associated with differential age, degrees of chemosensory loss, and regional patterns. Uncovering the self-reported phenomenology of recovery from smell, taste, and chemesthetic disorders is the first, yet essential step, to provide healthcare professionals with the tools to take purposeful and targeted action to address chemosensory disorders and its severe discomfort.
    • Genetic and Cell biology Discriminants of Sars-CoV2 Infection and Susceptibility to Covid-19 pulmonary complication

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-05-04)
      The agent of Covid19, Sars-CoV-2 has caused thousands of fatalities worldwide and overshadowed the number of deaths of other previous coronavirus outbreaks (Sars-CoV1 2002 and MERS-CoV 2012). Although the new coronavirus pathogenicity is actively under investigation, part of its infectious behavior can be linked to its higher binding affinity to the angiotensin-converting enzyme 2 (ACE2) in the respiratory tracts. However, the expression of ACE2 per se may not be sufficient to justify the individual variability observed among affected patients in terms of clinical outcome in apparently non-immune depressed, non-elders subjects. The present update provides an overview of the most recent scientific findings related to genetic factors involved in the Sars-CoV-2 infectious process and their potential role in affecting the virus pathogenicity. The present update can provide valuable hints towards developing a predictive screening/susceptibility profile testing on individuals not yet infected and/or in non symptomatic positive subjects towards managing the current morbidity and mortality risk and establishing personalized intervention protocols for the early treatment of the Sars-CoV-2-associated life-threatening pulmonary complication.
    • Genetic and non-genetic factors affecting the expression of COVID-19-relevant genes in the large airway epithelium

      NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study(SPIROMICS); NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium (2021-04-21)
      Background: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression. Methods: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with and without chronic obstructive pulmonary disease (COPD) and replicated these associations in two asthma cohorts, SARP and MAST. To identify airway biology beyond ACE2 binding that may contribute to increased susceptibility, we used gene set enrichment analyses to determine if gene expression changes indicative of a suppressed airway immune response observed early in SARS-CoV-2 infection are also observed in association with host factors. To identify host genetic variants affecting COVID-19 susceptibility in SPIROMICS, we performed expression quantitative trait (eQTL) mapping and investigated the phenotypic associations of the eQTL variants. Results: We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. Conclusions: These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.
    • Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

      Faria, Nuno R.; Mellan, Thomas A.; Whittaker, Charles; Claro, Ingra M.; Candido, Darlan da S.; Mishra, Swapnil; Crispim, Myuki A. E.; Sales, Flavia C.S.; Hawryluk, Iwona; McGrone, John T.; Hulswit, Ruben J.G.; Franco, Lucas A.M.; Ramundo, Mariana S.; De Jesus, Jaqueline G.; Andrade, Pamela S.; Coletti, Thais M.; Ferreira, Giulia M.; Silva, Camila A.M.; Manuli, Erika R.; Pereira, Rafael H.M.; Peixoto, Pedro S.; Kraemaer, Moritz U.G.; Gaburo Jr., Nelson; Camilo, Cecilia da C.; Hoeltgebaum, Henrique; Souza, William M.; Rocha, Esmenia C.; de Souza, Leandro M.; de Pinho, Mariana C.; Araujo, Leonardo J.T.; Malta, Frederico S.V.; de Lima, Aline B.; Silva, Joice do P.; Zauli, Danielle A.G.; Ferreira, Alessandro C. de S.; Schnekenberg, Ricardo P.; Laydon, Daniel J.; Walker, Patrick G.T.; Schluter, Hannah M.; dos Santos, Ana L.P.; Vidal, Maria S.; Del Caro, Valentina S.; Filho, Rosinaldo M.F.; dos Santos, Helem M.; Aguiar, Renato S.; Proenca-Modena, Jose L.; Nelson, Bruce; Hay, James A.; Monod, Melodie; Miscouridou, Xenia; Coupland, Helen; Sonabend, Raphael; Vollmer, Michaela; Gandy, Axel; Prete Jr., Carlos A.; Nascimento, Vitor H.; Suchard, Marc A.; Bowden, Thomas A.; Pond, Sergei; Wu, Chieh-Hsi; Ratmann, Oliver; Ferguson, Neil M.; Dye, Christopher; Loman, Nick J.; Lemey, Philippe; Rambaut, Andrew; Fraiji, Nelson A.; Carvalho, Maria do P.S.S.; Pybus, Oliver G.; Flaxman, Seth; Bhatt, Samir; Sabino, Ester C.; Pond|0000-0003-4817-4029 (2021-05-21)
      Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.
    • Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease

      GOLD Science Committee (2021-01-01)
      The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required. It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic. It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2. During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery. Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering. Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination. Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management. Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications. Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging. If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered. Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation. Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome. Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols. Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy.
    • Guillain-Barre Syndrome in a Patient With Asymptomatic Coronavirus Disease 2019 Infection and Major Depressive Disorder

      Mokhashi, Nikita; Narla, Gowtham; Marchionni, Christine; Mokhashi|0000-0001-9510-3747 (2021-03-28)
      Coronavirus disease 2019 (COVID-19) has had a devastating effect on all aspects of society, including the economy, healthcare, and educational institutions. One underrecognized effect of the pandemic is the decline of mental health in our communities. Studies have shown that pandemic-related stress is associated with increased depression and anxiety. In addition to worsening mental health, COVID-19 infection has been shown to have neurological manifestations. We report the case of a 56-year-old woman with a history of major depressive disorder and alcohol use with no recent history of infection or vaccination who presented with hand and foot paresthesias over the past six weeks, 30 lb weight loss, dysphoric mood, and acutely progressive ambulatory dysfunction over the past two weeks, for which she required assistance to ambulate. Psychiatric evaluation was significant for depressive symptoms. On neurologic examination, she had decreased deep tendon reflexes and ataxic, jerky gait. She was found to be positive for COVID-19. Labs and findings demonstrated albuminocytologic dissociation which suggests presumptive diagnosis of Guillain-Barre syndrome, prompting treatment with intravenous immunoglobulin for five days. She was noted to be deficient in zinc, folate, copper, and borderline B-12, as well as mild hyponatremia, hypokalemia, and hypomagnesemia likely secondary to depression-induced loss of appetite and alcohol use disorder. Guillain-Barre is a severe and debilitating outcome that must be considered when evaluating neuromuscular weakness in the setting of COVID-19, even in asymptomatic patients. Our case highlights the multifactorial intersection between Guillain-Barre syndrome, COVID-19, and concomitant mental health and alcohol use disorder.
    • Healthcare resource use among solid organ transplant recipients hospitalized with COVID‐19

      Heldman, Madeleine R.; Kates, Olivia S.; Haydel, Brandy M.; Florman, Sander S.; Rana, Meenakshi M.; Chaudhry, Zohra S.; Ramesh, Mayur S.; Safa, Kassem; Kotton, Camille N.; Blumberg, Emily A.; Besharatian, Behdad D.; Tanna, Sajal D.; Ison, Michael G.; Malinis, Maricar; Azar, Marwan M.; Rakita, Robert M.; Morillas, Jose A.; Majeed, Aneela; Sait, Afrah S.; Spaggiari, Mario; Hemmige, Vagish; Mehta, Sapna A.; Neumann, Henry; Badami, Abbasali; Jeng, Amy; Goldman, Jason D.; Lala, Anuradha; Hemmersbach‐Miller, Marion; McCort, Margaret E.; Bajrovic, Valida; Ortiz‐Bautista, Carlos; Friedman‐Moraco, Rachel; Sehgal, Sameep; Lease, Erika D.; Limaye, Ajit P.; Fisher, Cynthia E. (2020-12-22)
    • Heart failure in COVID‐19: the multicentre, multinational PCHF‐COVICAV registry

      Sokolski, Mateusz; Trenson, Sander; Sokolska, Justyna M.; D'Amario, Domenico; Meyer, Philippe; Poku, Nana K.; Biering-Sørensen, Tor; Højbjerg Lassen, Mats C.; Skaarup, Kristoffer G.; Barge-Caballero, Eduardo; Pouleur, Anne-Catherine; Stolfo, Davide; Sinagra, Gianfranco; Ablasser, Klemens; Muster, Viktoria; Rainer, Peter P.; Wallner, Markus; Chiodini, Alessandra; Heiniger, Pascal S.; Mikulicic, Fran; Schwaiger, Judith; Winnik, Stephan; Cakmak, Huseyin A.; Gaudenzi, Margherita; Mapelli, Massimo; Mattavelli, Irene; Paul, Matthias; Cabac-Pogorevici, Irina; Bouleti, Claire; Lilliu, Marzia; Minoia, Chiara; Dauw, Jeroen; Costa, Jérôme; Celik, Ahmet; Mewton, Nathan; Montenegro, Carlos E.L.; Matsue, Yuya; Loncar, Goran; Marchel, Michal; Bechlioulis, Aris; Michalis, Lampros; Dörr, Marcus; Prihadi, Edgard; Schoenrath, Felix; Messroghli, Daniel R.; Mullens, Wilfried; Lund, Lars H.; M.C. Rosano, Giuseppe; Ponikowski, Piotr; Ruschitzka, Frank; Flammer, Andreas J.; Wallner|0000-0001-7692-892X (2021-09-17)
      Aims: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. Methods and results: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62–81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44–2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01–2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24–4.29], P < 0.001). Conclusions: Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality.
    • History of Respiratory Stimulants

      Peppin, John F.; Pergolizzi Jr., Joseph V.; Fudin, Jeffrey; Meyer, Tricia A.; Raffa, Robert B. (2021-04-16)
      The interest in substances that stimulate respiration has waxed and waned throughout the years, intensifying following the introduction of a new class of drugs that causes respiratory depression, and diminishing when antidotes or better drug alternatives are found. Examples include the opioids––deaths increasing during overprescribing, diminishing with wider availability of the opioid receptor antagonist naloxone, increasing again during COVID-19; the barbiturates––until largely supplanted by the benzodiazepines; propofol; and other central nervous system depressants. Unfortunately, two new troubling phenomena force a reconsideration of the status-quo: (1) overdoses due to highly potent opioids such as fentanyl, and even more-potent licit and illicit fentanyl analogs, and (2) overdose due to polysubstance use (the combination of an opioid plus one or more non-opioid drug, such as a benzodiazepine, sedating antidepressant, skeletal muscle relaxant, or various other agents). Since these now represent the majority of cases, new solutions are again needed. An interest in respiratory stimulants has been revived. This interest can be informed by a short review of the history of this interesting class of medications. We present a short history of the trajectory of advances toward more selective and safer respiratory stimulants.
    • HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-08-25)
      Tumor-infiltrating T cell rescue by programmed cell death receptor-1 (PD-1)/PD-1 ligand-1 (PD-L1) immune checkpoint blockade is a recommended treatment for malignant diseases, including metastatic non-small-cell lung cancer (mNSCLC), malignant melanoma (MM), head and neck, kidney, and urothelial cancer. Monoclonal antibodies (mAbs) against either PD-1 or PD-L1 are active agents for these patients; however, their use may be complicated by unpredictable immune-related adverse events (irAEs), including immune-related pneumonitis (IRP). We carried out a retrospective multi-institutional statistical analysis to investigate clinical and biological parameters correlated with IRP rate on a cohort of 256 patients who received real-world treatment with PD-1/PD-L1 blocking mAbs. An independent radiological review board detected IRP in 29 patients. We did not find statistical IRP rate correlation with gender, tumor type, specific PD-1 or PD-L1 blocking mAbs, radiation therapy, inflammatory profile, or different irAEs. A higher IRP risk was detected only in mNSCLC patients who received metronomic chemotherapy +/− bevacizumab compared with other treatments prior PD-1/PD-L1 blockade. Moreover, we detected a strong correlation among the IRP rate and germinal expression of HLA-B*35 and DRB1*11, alleles associated to autoimmune diseases. Our findings may have relevant implications in predicting the IRP rate in mNSCLC patients receiving PD-1/PD-L1 blockade and need to be validated on a larger patient series.
    • HLA-B*44 and C*01 Prevalence Correlates with Covid19 Spreading across Italy

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-07-23)
      The spread of COVID-19 is showing huge, unexplained, differences between northern and southern Italy. We hypothesized that the regional prevalence of specific class I human leukocyte antigen (HLA) alleles, which shape the anti-viral immune response, might partly underlie these differences. Through an ecological approach, we analyzed whether a set of HLA alleles (A, B, C), known to be involved in the immune response against infections, correlates with COVID-19 incidence. COVID-19 data were provided by the National Civil Protection Department, whereas HLA allele prevalence was retrieved through the Italian Bone-Marrow Donors Registry. Among all the alleles, HLA-A*25, B*08, B*44, B*15:01, B*51, C*01, and C*03 showed a positive log-linear correlation with COVID-19 incidence rate fixed on 9 April 2020 in proximity of the national outbreak peak (Pearson’s coefficients between 0.50 and 0.70, p-value < 0.0001), whereas HLA-B*14, B*18, and B*49 showed an inverse log-linear correlation (Pearson’s coefficients between −0.47 and −0.59, p-value < 0.0001). When alleles were examined simultaneously using a multiple regression model to control for confounding factors, HLA-B*44 and C*01 were still positively and independently associated with COVID-19: a growth rate of 16% (95%CI: 0.1–35%) per 1% point increase in B*44 prevalence; and of 19% (95%CI: 1–41%) per 1% point increase in C*01 prevalence. Our epidemiologic analysis, despite the limits of the ecological approach, is strongly suggestive of a permissive role of HLA-C*01 and B*44 towards SARS-CoV-2 infection, which warrants further investigation in case-control studies. This study opens a new potential avenue for the identification of sub-populations at risk, which could provide Health Services with a tool to define more targeted clinical management strategies and priorities in vaccination campaigns.
    • Homemade Face Shield Assembly Guide

      TUCAT (Temple University) (2020-05-07)
    • Human-Dog Relationship during the First COVID-19 Lockdown in Italy

      Sbarro Institute for Cancer Research and Molecular Medicine (Temple University); Center for Biotechnology (Temple University) (2021-08-07)
      The SARS-CoV2 pandemic forced an abrupt interruption of social contacts and interpersonal affective relationships all over the world, according to national directives. Many considerable inconveniences occurred with important repercussions also on the emotional state of people and their pets. We carried out a national survey to evaluate the human-dog relationship in a social isolation context using an adapted version of Monash Dog Owner Relationship Scale, the perception of the dogs’ discomfort by their human owners, and the resilience of the dog through the quantification of symptoms, in time of the first lockdown of the COVID-19 pandemic. The results highlighted that the human-dog interaction was similar during quarantine; however, there was lower owner’s perception of a dog’s cost during the quarantine than before it.
    • IEEE Access Special Section Editorial: Security and Privacy in Emerging Decentralized Communication Environments

      Cheng, Xiaochun; Liu, Zheli; DU, XIAOJIANG; Yu, Shui; Mostarda, Leonardo; Du|0000-0003-4235-9671 (2021-05-13)
      Due to the COVID-19 epidemic, face-to-face team working has changed into distanced work from home. Modern, decentralized digital communication environments are changing with the availability of new technologies and the development of new real-world applications, which lead to novel challenges in security and privacy protection. 5G/6G mobile applications, the smart Internet of Things (IoT) devices, big data applications, and cloud systems are developing to better meet new requirements. Mobile–cloud architecture is emerging as 5G /6G mobile IoT devices are generating large volumes of data which need cloud infrastructure to process. Many IoT systems and cloud systems are decentralized, and new security and privacy protection solutions are emerging in decentralized networks. The increasing interdependence of IT solutions accepted by society has led to a sharp increase in data. As a result, the chances of data leakage or privacy infringement also increase, along with the need for new solutions for digital security and privacy protection.