Publications by authors named "Silvia Angeletti"

164 Publications

SARS-CoV-2 B.1.617 Indian variants: Are electrostatic potential changes responsible for a higher transmission rate?

J Med Virol 2021 Jul 14. Epub 2021 Jul 14.

Center of of Genomics, Genetics and Biology, Siena, Italy.

Lineage B.1.617+, also known as G/452R.V3 and now denoted by WHO with the Greek letters δ and κ, is a recently described SARS-CoV-2 variant under investigation first identified in October 2020 in India. As of May 2021, three sublineages labeled as B.1.617.1 (κ), B.1.617.2 (δ), and B.1.617.3 have been already identified, and their potential impact on the current pandemic is being studied. This variant has 13 amino acid changes, three in its spike protein, which are currently of particular concern: E484Q, L452R, and P681R. Here, we report a major effect of the mutations characterizing this lineage, represented by a marked alteration of the surface electrostatic potential (EP) of the receptor-binding domain (RBD) of the spike protein. Enhanced RBD-EP is particularly noticeable in the B.1.617.2 (δ) sublineage, which shows multiple replacements of neutral or negatively charged amino acids with positively charged amino acids. We here hypothesize that this EP change can favor the interaction between the B.1.617+ RBD and the negatively charged ACE2, thus conferring a potential increase in the virus transmission.
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http://dx.doi.org/10.1002/jmv.27210DOI Listing
July 2021

The variants question: What is the problem?

J Med Virol 2021 Jul 13. Epub 2021 Jul 13.

Medical Statistic and Molecular Epidemiology Unit, University of Biomedical Campus, Rome, Italy.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole-genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS-CoV-2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called "variants of concerns" (VOCs), and/or "variants of interests" (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS-CoV-2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS-CoV-2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS-CoV-2 threat to better understand the virus genetic diversity and its potential impact on vaccination strategy.
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http://dx.doi.org/10.1002/jmv.27196DOI Listing
July 2021

Detection of a SARS-CoV-2 P.1.1 variant lacking N501Y in a vaccinated health care worker in Italy.

J Infect 2021 Jul 6. Epub 2021 Jul 6.

Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Italy.

Vaccines against SARS-CoV-2 are very effective, but some mutations could reduce protection. Here we report a case of SARS-CoV-2 infection with a P.1.1 variant lacking the Y501 mutation in a vaccinated individual in Italy. Carefully monitoring breakthrough infections is important for assessing viral spreading of potential vaccine-resistant variants.
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http://dx.doi.org/10.1016/j.jinf.2021.06.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257417PMC
July 2021

COVID-19 sniffer dog experimental training: Which protocol and which implications for reliable sidentification?

J Med Virol 2021 Jun 21. Epub 2021 Jun 21.

Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy.

The introduction of trained sniffer dogs for COVID-19 detection could be an opportunity, as previously described for other diseases. Dogs could be trained to detect volatile organic compounds (VOCs), the whiff of COVID-19. Dogs involved in the study were three, one male and two females from different breeds, Black German Shepherd, German Shepherd, and Dutch Shepherd. The training was performed using sweat samples from SARS-CoV2 positive patients and from SARS-Cov2 free patients admitted at the University Hospital Campus Bio-medico of Rome. Gauze with sweat was collected in a glass jar with a metal top and put in metal boxes used for dog training. The dog training protocol was performed in two phases: the olfactory conditioning and the olfactory discrimination research. The training planning was focused on the switch moment for the sniffer dog, the moment when the dog was able to identify VOCs specific for COVID-19. At this time, the dog was able to identify VOCs specific for COVID-19 with significant reliability, in terms of the number of correct versus incorrect (p < 0.0001) reporting. In conclusion, this protocol could provide a useful tool for sniffer dogs' training and their introduction in a mass screening context. It could be cheaper and faster than a conventional testing method.
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http://dx.doi.org/10.1002/jmv.27147DOI Listing
June 2021

CA19.9 Serum Level Predicts Lymph-Nodes Status in Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis.

Front Oncol 2021 27;11:690580. Epub 2021 May 27.

Department of Surgery, Campus Bio-Medico University, Rome, Italy.

Background: The choice between upfront surgery or neoadjuvant treatments (NAT) for resectable pancreatic ductal adenocarcinoma (R-PDAC) is controversial. R-PDAC with potential nodal involvement could benefit from NT. Ca (Carbohydrate antigen) 19.9 and serum albumin levels, alone or in combination, have proven their efficacy in assessing PDAC prognosis. The objective of this study was to evaluate the role of Ca 19.9 serum levels in predicting nodal status in R-PDAC.

Methods: Preoperative Ca 19.9, as well as serum albumin levels, of 165 patients selected for upfront surgery have been retrospectively collected and correlated to pathological nodal status (N), resection margins status (R) and vascular resections (VR). We further performed ROC curve analysis to identify optimal Ca 19.9 cut-off for pN+, R+ and vascular resection prediction.

Results: Increased Ca 19.9 levels in 114 PDAC patients were significantly associated with pN+ (p <0.001). This ability, confirmed in all the series by ROC curve analysis (Ca 19.9 ≥32 U/ml), was lost in the presence of hypoalbuminemia. Furthermore, Ca 19.9 at the cut off >418 U/ml was significantly associated with R+ (87% specificity, 36% sensitivity, p 0.014). Ca 19.9, at the cut-off >78 U/ml, indicated a significant trend to predict the need for VR (sensitivity 67%, specificity 53%; p = 0.059).

Conclusions: In R-PDAC with normal serum albumin levels, Ca 19.9 predicts pN+ and R+, thus suggesting a crucial role in deciding on NAT.
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http://dx.doi.org/10.3389/fonc.2021.690580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190389PMC
May 2021

Different Biliary Microbial Flora Influence Type of Complications after Pancreaticoduodenectomy: A Single Center Retrospective Analysis.

J Clin Med 2021 May 18;10(10). Epub 2021 May 18.

Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy.

Background: Bacterobilia is associated with postoperative morbidity after pancreaticoduodenectomy (PD), mostly due to infectious complications. The aim of this study was to investigate the prevalence of bacteria species isolated from intraoperative biliary cultures, and related complications after PD.

Methods: An ANOVA test was used to assess the prevalence of isolated bacterial species and postoperative complications. The odds ratio was computed to evaluate the association between biliary cultures and each complication, Endoscopic Retrograde CholangioPancreatography (ERCP) and each complication, ERCP and biliary cultures, Delayed Gastric Emptying (DGE) and Postoperative Pancreatic Fistula (POPF).

Results: Positive biliary cultures were found in 162/244 (66%) PDs. Different prevalences of polymicrobial biliary culture were detected in patients with postoperative complications. In SSIs, a significant prevalence of biliary culture positive for , and ( < 0.001) was detected. Prevalences of polymicrobial biliary cultures with , , and were significantly associated with POPF ( < 0.001). Biliary culture positive for , and showed a higher prevalence of intra-abdominal collection and DGE ( < 0.001). Notably, was significantly associated with DGE as a unique complication (OR = 2.94 (1.30-6.70); < 0.01).

Conclusions: Specific prevalences of polymicrobial bacterobilia are associated with major complications, while monomicrobial bacterobilia is associated with DGE as a unique complication after PD.
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http://dx.doi.org/10.3390/jcm10102180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157867PMC
May 2021

Betacoronaviruses genome analysis reveals evolution toward specific codons usage: Implications for SARS-CoV-2 mitigation strategies.

J Med Virol 2021 09 24;93(9):5630-5634. Epub 2021 May 24.

Laboratório de Genética Celular e Molecular, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly widespread worldwide becoming one of the major global public health issues of the last centuries. Currently, COVID-19 vaccine rollouts are finally upon us carrying the hope of herd immunity once a sufficient proportion of the population has been vaccinated or infected, as a new horizon. However, the emergence of SARS-CoV-2 variants brought concerns since, as the virus is exposed to environmental selection pressures, it can mutate and evolve, generating variants that may possess enhanced virulence. Codon usage analysis is a strategy to elucidate the evolutionary pressure of the viral genome suffered by different hosts, as possible cause of the emergence of new variants. Therefore, to get a better picture of the SARS-CoV-2 codon bias, we first identified the relative codon usage rate of all Betacoronaviruses lineages. Subsequently, we correlated putative cognate transfer ribonucleic acid (tRNAs) to reveal how those viruses adapt to hosts in relation to their preferred codon usage. Our analysis revealed seven preferred codons located in three different open reading frame which appear preferentially used by SARS-CoV-2. In addition, the tRNA adaptation analysis indicates a wide strategy of competition between the virus and mammalian as principal hosts highlighting the importance to reinforce the genomic monitoring to prompt identify any potential adaptation of the virus into new potential hosts which appear to be crucial to prevent and mitigate the pandemic.
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http://dx.doi.org/10.1002/jmv.27056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242727PMC
September 2021

Association between Dietary Habits and Fecal Microbiota Composition in Irritable Bowel Syndrome Patients: A Pilot Study.

Nutrients 2021 Apr 27;13(5). Epub 2021 Apr 27.

Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy.

Intestinal dysbiosis seems to play a role in the pathophysiology of irritable bowel syndrome (IBS). The present pilot study aimed to elucidate the association between nutrient intake and Mediterranean diet (MD) adherence with IBS symptoms and gut microbiota in IBS patients. The nutrient intake of 28 IBS patients and 21 controls was assessed through a food diary, the reference intake ranges (RIs) for energy-yielding macronutrients and the MD serving score (MDSS) index. MD adherence and nutrients intake were compared to IBS symptoms and fecal microbiota, obtained by 16S rRNA targeted-metagenomics. In IBS patients MDSS index was altered compared to controls ( < 0.01). IBS patients with low-MD score reported severe abdominal pain and higher flatulence point-scales. Through Linear discriminant analysis effect size (LEfSe), Erysipelotrichaceae were detected as a microbial biomarker in IBS patients with altered RIs for macronutrients intake, compared to controls. Lactobacillaceae and were associated to an altered carbohydrates intake in IBS patients, while specific taxonomic biomarkers, such as , Mogibacteriaceae, Rikenellaceae, and were associated with an adequate intake of nutrient in these patients. This study supports an association between dietary patterns and gut microbial biomarkers in IBS patients. Further investigations are needed to clarify these connections.
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http://dx.doi.org/10.3390/nu13051479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170891PMC
April 2021

SARS-CoV-2 shifting transmission dynamics and hidden reservoirs potentially limit efficacy of public health interventions in Italy.

Commun Biol 2021 04 21;4(1):489. Epub 2021 Apr 21.

Medical Statistic and Molecular Epidemiology Unit, University of Biomedical Campus, Rome, Italy.

We investigated SARS-CoV-2 transmission dynamics in Italy, one of the countries hit hardest by the pandemic, using phylodynamic analysis of viral genetic and epidemiological data. We observed the co-circulation of multiple SARS-CoV-2 lineages over time, which were linked to multiple importations and characterized by large transmission clusters concomitant with a high number of infections. Subsequent implementation of a three-phase nationwide lockdown strategy greatly reduced infection numbers and hospitalizations. Yet we present evidence of sustained viral spread among sporadic clusters acting as "hidden reservoirs" during summer 2020. Mathematical modelling shows that increased mobility among residents eventually catalyzed the coalescence of such clusters, thus driving up the number of infections and initiating a new epidemic wave. Our results suggest that the efficacy of public health interventions is, ultimately, limited by the size and structure of epidemic reservoirs, which may warrant prioritization during vaccine deployment.
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http://dx.doi.org/10.1038/s42003-021-02025-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060392PMC
April 2021

Perioperative management after elective cardiac surgery: the predictive value of procalcitonin for infective and noninfective complications.

Future Cardiol 2021 Apr 20. Epub 2021 Apr 20.

Geriatrics, Università Campus Bio-Medico di Roma, Rome 00128, Italy.

Procalcitonin (PCT) has been associated with adverse outcomes after cardiac surgery. Nevertheless, there is no consensus on thresholds and timing of PCT measurement to predict adverse outcomes. A total of 960 patients undergoing elective cardiac surgery were retrospectively evaluated. PCT levels were measured from the first to the seventh postoperative day (POD). The onset of complications was recorded. Complications occurred in 421 (44%) patients. PCT on the third POD was associated with the occurrence of any kind of complications (odds ratio: 1.06; p: 0.037), and noninfectious complications (odds ratio: 1.05; p: 0.035), after adjusting. PCT above the median value at the third POD (>0.33 μg/l) predicted postoperative complications (incidence rate ratio: 1.13; p = 0.035). PCT seems to predict postoperative complications in cardiac surgery. The determination at the third POD yields the greatest sensitivity and specificity.
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http://dx.doi.org/10.2217/fca-2020-0245DOI Listing
April 2021

The importance of genomic analysis in cracking the coronavirus pandemic.

Expert Rev Mol Diagn 2021 06 28;21(6):547-562. Epub 2021 Apr 28.

Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy.

: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has pushed the scientific community to undertake intense research efforts. Understanding SARS-CoV-2 biology is necessary to discover therapeutic or preventive strategies capable of containing the pandemic. Knowledge of the structural characteristics of the virus genome and proteins is essential to find targets for therapies and immunological interventions.: This review covers different areas of expertise, genomic analysis of circulating strains, structural biology, viral mutations, molecular diagnostics, disease, and vaccines. In particular, the review is focused on the molecular approaches and modern clinical strategies used in these fields.: Molecular approaches to SARS-CoV-2 pandemic have been critical to shorten time for new diagnostic, therapeutic and prevention strategies. In this perspective, the entire scientific community is moving in the same direction. Vaccines, together with the development of new drugs to treat the disease, represent the most important strategy to protect human from viral disease and prevent further spread. In this regard, new molecular technologies have been successfully implemented. The use of a novel strategy of communication is suggested for a better diffusion to the broader public of new data and results.
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http://dx.doi.org/10.1080/14737159.2021.1917998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095159PMC
June 2021

Animal Hosts and Experimental Models of SARS-CoV-2 Infection.

Chemotherapy 2021 26;66(1-2):8-16. Epub 2021 Mar 26.

National HIV/AIDS Research Center, Istituto Superiore di Sanità, Rome, Italy.

Viruses arise through cross-species transmission and can cause potentially fatal diseases in humans. This is the case of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which recently appeared in Wuhan, China, and rapidly spread worldwide, causing the outbreak of coronavirus disease 2019 (COVID-19) and posing a global health emergency. Sequence analysis and epidemiological investigations suggest that the most likely original source of SARS-CoV-2 is a spillover from an animal reservoir, probably bats, that infected humans either directly or through intermediate animal hosts. The role of animals as reservoirs and natural hosts in SARS-CoV-2 has to be explored, and animal models for COVID-19 are needed as well to be evaluated for countermeasures against SARS-CoV-2 infection. Experimental cells, tissues, and animal models that are currently being used and developed in COVID-19 research will be presented.
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http://dx.doi.org/10.1159/000515341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089426PMC
June 2021

Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection.

Chemotherapy 2021 23;66(1-2):24-32. Epub 2021 Mar 23.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.
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http://dx.doi.org/10.1159/000515344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089442PMC
June 2021

SARS-CoV-2 Infection and the COVID-19 Pandemic Emergency: The Importance of Diagnostic Methods.

Chemotherapy 2021 19;66(1-2):17-23. Epub 2021 Mar 19.

Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.

Background: Currently, a pandemic of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is underway, resulting in high morbidity and mortality across the globe.

Summary: A prompt and effective diagnosis is crucial to identify infected individuals, to monitor the infection, to perform contact tracing, and to limit the spread of the virus. Since the announcement of this public health emergency, several diagnostic methods have been developed including molecular and serological assays, and more recently biosensors. Here, we present the use of these assays as well as their main technical features, advantages, and limits. Key Messages: The development of reliable diagnostic assays is crucial not only for a correct diagnosis and containment of COVID-19 pandemic, but also for the decision-making process that is behind the clinical decisions, eventually contributing to the improvement of patient management. Furthermore, with the advent of vaccine and therapeutic monoclonal antibodies against SARS-CoV-2, serological assays will be instrumental for the validation of these new therapeutic options.
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http://dx.doi.org/10.1159/000515343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089410PMC
June 2021

Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department.

Expert Rev Mol Diagn 2021 04 29;21(4):397-404. Epub 2021 Mar 29.

Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.

Introduction: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians' decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature.

Areas Covered: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients' clinical pathways in an ED setting.

Expert Opinion: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician's decision making and recognizing the 'ill looking well' and the 'well looking ill' sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally.
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http://dx.doi.org/10.1080/14737159.2021.1902312DOI Listing
April 2021

The Bayesian reconstruction and the evolutionary history of Salivirus type 1 and type 2: the worldwide spreading.

J Infect Dev Ctries 2021 Mar 7;15(2):280-288. Epub 2021 Mar 7.

Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Italy.

Introduction: Salivirus (SalV) represents an emerging problem in public health especially during the recent years. In this study, the Bayesian evolutionary history and the spread of the virus through the different countries have been reported.

Methodology: a database of 81 sequences of SalV structural VP1 fragment were downloaded from GenBank, aligned and manually edited by Bioedit Software. ModelTest v. 3.7 software was used to estimate the simplest evolutionary model fitting the sequence dataset. A Maximum-Likelihood tree has been generated using MEGA-X to test the "clockliness" signal using TempEst 1.5.1. The Bayesian phylogenetic tree was built by BEAST. Homology modelling was performed by SWISS-Model and protein variability evaluated by ConSurf server.

Results: the phylogenetic tree showed a clade of SalV A2 and three main clades of SalV A1, revealing several infections in humans in South Korea, India, Tunisia, China, Nigeria, Ethiopia and USA. The Bayesian maximum clade credibility tree and the time of the most common recent ancestor dated back the root of the tree to the year 1788 with the probable origin in USA. Selective pressure analysis revealed two positive selection sites, His at 100th and Leu at 116th positions that at the homology modelling resulted important to guarantee protein stability and variability. This could contribute to the development of new mutations modifying the clinical features of this evolving virus.

Conclusions: Bayesian phylogenetic and phylodynamic represented a useful tool to follow the transmission dynamic of SalV and to prevent new epidemics worldwide.
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http://dx.doi.org/10.3855/jidc.12141DOI Listing
March 2021

Malaria in an asylum seeker paediatric liver transplant recipient: diagnostic challenges for migrant population.

J Infect Dev Ctries 2021 01 31;15(1):172-178. Epub 2021 Jan 31.

Migrant and global Health Research Organization (Mi-HeRO) Rome, Italy.

Transplanted patients are particularly exposed to a major risk of infectious diseases due to prolonged immunosuppressive treatment. Over the last decade, the growing migration flows and the transplant tourism have led to increasing infections caused by geographically restricted organisms. Malaria is an unusual event in organ transplant recipients than can be acquired primarily or reactivation following immunosuppression, by transfusion of blood products or through the transplanted organ. We report a rare case of Plasmodium falciparum infection in a liver transplanted two years-old African boy who presented to one Italian Asylum Seeker Center on May 2019. We outlined hereby diagnostic challenges, possible aetiologies of post-transplantation malaria and finally we summarized potential drug interactions between immunosuppressive agents and antimalarials. This report aims to increase the attention to newly arrived migrants, carefully evaluating patients coming from tropical areas and taking into consideration also rare tropical infections not endemic in final destination countries.
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http://dx.doi.org/10.3855/jidc.12541DOI Listing
January 2021

Deep Learning Algorithm Trained with COVID-19 Pneumonia Also Identifies Immune Checkpoint Inhibitor Therapy-Related Pneumonitis.

Cancers (Basel) 2021 Feb 6;13(4). Epub 2021 Feb 6.

Departmental Faculty of Medicine and Surgery, Unit of Diagnostic Imaging and Interventional Radiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy.

Background: Coronavirus disease 2019 (COVID-19) pneumonia and immune checkpoint inhibitor (ICI) therapy-related pneumonitis share common features. The aim of this study was to determine on chest computed tomography (CT) images whether a deep convolutional neural network algorithm is able to solve the challenge of differential diagnosis between COVID-19 pneumonia and ICI therapy-related pneumonitis.

Methods: We enrolled three groups: a pneumonia-free group ( = 30), a COVID-19 group ( = 34), and a group of patients with ICI therapy-related pneumonitis ( = 21). Computed tomography images were analyzed with an artificial intelligence (AI) algorithm based on a deep convolutional neural network structure. Statistical analysis included the Mann-Whitney U test (significance threshold at < 0.05) and the receiver operating characteristic curve (ROC curve).

Results: The algorithm showed low specificity in distinguishing COVID-19 from ICI therapy-related pneumonitis (sensitivity 97.1%, specificity 14.3%, area under the curve (AUC) = 0.62). ICI therapy-related pneumonitis was identified by the AI when compared to pneumonia-free controls (sensitivity = 85.7%, specificity 100%, AUC = 0.97).

Conclusions: The deep learning algorithm is not able to distinguish between COVID-19 pneumonia and ICI therapy-related pneumonitis. Awareness must be increased among clinicians about imaging similarities between COVID-19 and ICI therapy-related pneumonitis. ICI therapy-related pneumonitis can be applied as a challenge population for cross-validation to test the robustness of AI models used to analyze interstitial pneumonias of variable etiology.
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http://dx.doi.org/10.3390/cancers13040652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914551PMC
February 2021

The use of an implemented infection prevention bundle reduces the incidence of surgical site infections after colorectal surgery: a retrospective single center analysis.

Updates Surg 2021 Jan 5. Epub 2021 Jan 5.

Department of Surgery, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy.

Background: Surgical-site infections (SSIs) represent the most common complications after colorectal surgery (CS). Role of preoperative administration of oral antibiotic prophylaxis (OAP) and mechanical bowel preparation (MBP), alone or in combination, in the prevention of SSIs after CS is debated. Aim of this study was to assess the effect of the introduction of an Implemented Infection Prevention Bundle (IIPB) in preventing SSIs in CS.

Methods: A group of 251 patients (Group 1) who underwent CS receiving only preoperative intravenous antibiotic prophylaxis (IAP) was compared to a Group of 107 patients (Group 2) who also received the IIPB. The IIPB consisted of the combination of oral administrations of three doses of Rifaximin 400 mg and MBP the day before surgery and in the administration of a cleansing enema the day of the surgical procedure.

Results: At the univariate analysis, Group 2 showed significant lower rates of wound infection (WI) (2.8% vs. 9.9%; p = 0.021) and anastomotic leakage (AL) (2.8% vs. 14.7%; p = 0.001) with shorter hospital stay (5 vs. 6 days; p < 0.0001). The probability of postoperative AL was lower in Group 2; patients in this Group resulted protected from AL; a statistically significant Odds ratio of 0.16 (CI 0.05-0.55 p = 0.0034) was found. In diabetic patients, that were at higher risk of WI (OR 3.53, CI 1.49-8.35 p = 0.002), despite having any impact on anastomotic dehiscence, the use of IIPB significantly reduced the rate of WI (0% vs 28.1%; p = 0.01).

Conclusion: The use of an IIPB significantly reduces rates of SSIs and post-operative hospital stay after CS.
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http://dx.doi.org/10.1007/s13304-020-00960-xDOI Listing
January 2021

The Pregnancy Outcomes Among Newly Arrived Asylum-Seekers in Italy: Implications of Public Health.

J Immigr Minor Health 2021 Apr 5;23(2):232-239. Epub 2020 Dec 5.

Department of Public Health and Infectious Diseases, Policlinico Umberto I Hospital. University of Rome Sapienza, Rome, Italy.

Background: Migration has a significant impact on overall health and pregnancy outcome. Despite the fact that growing volume of migration flows significantly engaging the public health system of European host countries, there is a lack of evidence concerning pregnancy outcomes of newly arrived asylum-seeking women.

Methods: Data about pregnant asylum seekers hosted in the Italian Reception Centers between the 1 st June 2016 and the 1st June 2018 were retrospectively collected and analysed in the present study. We examined the following pregnancy outcomes: miscarriage, self-induced abortion, voluntary pregnancy termination, live-birth; and studied potentially related socio-demographic factors.

Results: Out of the 110 pregnant women living in the reception centers, 44 (40%) had eutocic delivery, 8 (7.3%) dystocic delivery, 15 (13.6%) miscarriage, 17 (15.5%) self-induced abortion and 26 (23.6%) underwent voluntary pregnancy termination. Nigerian women were at a significantly higher risk of abortive outcomes for voluntary pregnancy termination (p < 0.001), miscarriage (p = 0.049) and self-induced abortion (p < 0.001). Being unmarried was significantly associated with voluntary pregnancy termination and self-induced abortion. Women who chose to undergo unsafe abortion did not result to have significantly lower educational levels, compared to women who preferred medical abortion.

Conclusion: This study offers first insights into pregnancy outcomes among asylum-seeking women in Italy. The country of origin and marital status seem to significantly impact on pregnancy outcome. We identified sub-groups of migrant women at increased risk of abortive outcomes, and highlight the need to improve care in order to promote migrant women's reproductive health.
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http://dx.doi.org/10.1007/s10903-020-01126-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914189PMC
April 2021

High value of mid-regional proadrenomedullin in COVID-19: A marker of widespread endothelial damage, disease severity, and mortality.

J Med Virol 2021 05 19;93(5):2820-2827. Epub 2021 Feb 19.

Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy.

The widespread endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi-organs dysfunction. The aim of this study was to evaluate the role of mid-regional proadrenomedullin (MR-proADM) as a marker of SARS-CoV2 related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS-CoV-2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR-proADM cut-off values for ARDS development and mortality prediction were 3.04 and 2 nmol/L, respectively. Patients presenting with MR-proADM values ≥2 nmol/L showed a significantly higher mortality risk. In conclusion, MR-proADM values ≥2 nmol/L identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach.
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http://dx.doi.org/10.1002/jmv.26676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753433PMC
May 2021

Evolution patterns of SARS-CoV-2: Snapshot on its genome variants.

Biochem Biophys Res Commun 2021 01 6;538:88-91. Epub 2020 Nov 6.

Medical Statistic and Molecular Epidemiology Unit, University of Biomedical Campus, Rome, Italy. Electronic address:

An acute respiratory syndrome (COVID-19), caused by a novel coronavirus (SARS-CoV-2) with a high rate of morbidity and elevate mortality, has emerged as one of the most important threats to humankind in the last centuries. Rigorous determination of SARS-CoV-2 infectivity is very difficult owing to the continuous evolution of the virus, with its single nucleotide polymorphism (SNP) variants and many lineages. However, it is urgently necessary to study the virus in depth, to understand the mechanism of its pathogenicity and virulence, and to develop effective therapeutic strategies. The present contribution summarizes in a succinct way the current knowledge on the evolutionary and structural features of the virus, with the aim of clarifying its mutational pattern and its possible role in the ongoing pandemic.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836704PMC
January 2021

Cost-effectiveness analysis of O-Ring wound retractor in elective laparoscopic colorectal surgery.

Ann Ital Chir 2020 Nov 2;9. Epub 2020 Nov 2.

Introduction: Surgical site infections (SSIs) are a feared complication following colorectal surgery and have a sizeable economic impact on the healthcare system. The aim of this study is to assess the clinical effectiveness and cost-effectiveness of O-Ring wound protector/retractor in elective laparoscopic colorectal surgery.

Methods: Data were analyzed from a retrospective colorectal database from January 2015 to June 2018. SSI was defined according to the criteria published by the European Centre for Disease Prevention and Control (ECDC). An economic evaluation was conducted comparing the group in which Alexis® device was used during surgery (Group A) with a control group (Group B) in which Alexis® device was not used.

Results: Two hundred fifty-eight consecutive patients were enrolled in our study. Among them, the intervention group (Group A, 154 patients) was compared with the control group (Group B, 94 patients). A total of 8 (5.2%) and 14 (15%) patients with SSIs were identified in groups A and B, respectively (p = 0.008). The economic evaluation showed that there was no difference in terms of costs and returns on comparing both groups.

Conclusion: The final costs and profit are similar in both groups, but the use of O-Ring protector reduces SSI rates and may significantly improve patient's quality of life.

Key Words: Colorectal surgery, Cost-effectiveness, Surgical site infection, Length of stay, Wound protector/retractor.
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November 2020

A Coinfection on a COVID-19 Pneumonia in a Breast Cancer Patient.

Int J Gen Med 2020 30;13:729-733. Epub 2020 Sep 30.

Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy.

Introduction: Coronavirus disease 19 (COVID-19), due to (SARS-CoV2), comprises a broad spectrum of clinical presentation ranging from flu-like syndrome to organ failure. The risk of coinfections is high and responsible for a worse prognosis, mainly in the case of bacterial involvement and in the presence of particular comorbidity. We present the clinical, laboratory, radiologic characteristic along with therapeutic management of a patient with COVID-19 and coinfection.

Case Presentation: A 55-year-old Caucasian woman was admitted to our hospital due to a two-day history of fever and acute dyspnea with severe respiratory failure worsened after the administration of atezolizumab and nab-paclitaxel. Her medical history comprehended a triple negative, -related, PD-L1 positive right breast cancer with multiple bone metastasis, causing bone marrow infiltration-related severe pancytopenia. Her physical examination revealed scattered wheezes, rales, and bilateral dry crackles in the middle and lower lung fields and lower limb paresis. The body mass index was 30 kg/m and arterial blood gas evaluation revealed a stage III acute respiratory distress syndrome. Microbiological specimens revealed a positivity from endotracheal aspirate. The chest computed tomography (CT) scan showed the presence of large areas of parenchymal consolidation and aerial bronchogram, bilateral "ground glass" areas reaching the highest extension on the upper and middle zones. The high clinical and radiological suspicion of COVID-19 along with the negative result of nasopharyngeal specimen make necessary an endotracheal aspirate resulting positive for SARS-CoV2. Patient started an antimicrobial treatment and lopinavir-ritonavir plus hydroxychloroquine but, unfortunately, died five days after hospital admission.

Conclusion: The high risk of mortality of our patient was due to viral-bacterial coinfection, advanced cancer status with active immunotherapy. This case highlights the need for a prompt clinical, laboratory, and radiological evaluation to allow a correct diagnosis and start a specific therapy.
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http://dx.doi.org/10.2147/IJGM.S261760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533271PMC
September 2020

Procalcitonin in the Assessment of Ventilator Associated Pneumonia: A Systematic Review.

Adv Exp Med Biol 2021 ;1323:103-114

Azienda Policlinico Umberto I, Rome, Italy.

Background: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infection, associated with considerable mortality and morbidity in critically ill patients; however, its diagnosis and management remain challenging since clinical assessment is often poorly reliable. The aim of this systematic review was to evaluate the role of PCT in the diagnosis and management of critical ill patients affected by VAP.

Methods: We performed a systematic review of the evidence published over the last 10 years and currently available in medical literature search databases (Pubmed, Embase, Web of Knowledge, Cochrane Libraries) and searching clinical trial registries. We regarded as predefined outcomes the role of PCT in diagnosis, therapeutic monitoring, antibiotic discontinuation and prognosis. The Open Science Framework Registration number was doi.org/10.17605/OSF.

Io/zgfkq Results: 761 articles were retrieved and a total of 18 studies (n° of patients = 1774) were selected and analyzed according to inclusion criteria. In this 2020 update, the systematic review showed that currently, conflicting and inconclusive data are available about the role of PCT in the diagnosis of VAP and in the prediction (i) of the efficacy of antibiotic therapy, and (ii) of the clinical outcome. These studies, instead, seem to agree on the utility of PCT in the management of antibiotic therapy discontinuation.

Conclusions: Currently there is insufficient evidence to support the role of PCT in the routine assessment of patients with VAP. The value of the results published appears to be limited by the deep methodological differences that characterize the various studies available at the present being.
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http://dx.doi.org/10.1007/5584_2020_591DOI Listing
April 2021

Best diagnostic accuracy of sepsis combining SIRS criteria or qSOFA score with Procalcitonin and Mid-Regional pro-Adrenomedullin outside ICU.

Sci Rep 2020 10 6;10(1):16605. Epub 2020 Oct 6.

Unit of Clinical Laboratory Science, University Campus Bio-Medico, Rome, Italy.

Early diagnosis and treatment significantly reduce sepsis mortality. Currently, no gold standard has been yet established to diagnose sepsis outside the ICU. The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS Criteria of 1991, Second Consensus Conference Criteria of 2001, modified Second Consensus Conference Criteria of 2001 (obtaining SIRS Criteria and SOFA score), Third Consensus Conference of 2016, in addition to the dosage of Procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM). In this prospective study, 209 consecutive patients with clinical diagnosis of sepsis were enrolled (May 2014-June 2018) outside intensive care unit (ICU) setting. A diagnostic protocol could include SIRS criteria or qSOFA score evaluation, rapid testing of PCT and MR-proADM, and SOFA score calculation for organ failure definition. Using this approach outside the ICU, a rapid diagnostic and prognostic evaluation could be achieved, also in the case of negative SIRS, qSOFA or SOFA scores with high post-test probability to reduce mortality and improve outcomes.
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http://dx.doi.org/10.1038/s41598-020-73676-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538435PMC
October 2020

qSOFA as a new community-acquired pneumonia severity score in the emergency setting.

Emerg Med J 2020 Oct 6. Epub 2020 Oct 6.

Department of Public Health and Infectious Diseases, University of Rome La Sapienza, Roma, Lazio, Italy.

Background: Quick Sequential Organ Failure Assessment (qSOFA) score is a bedside prognostic tool for patients with suspected infection outside the intensive care unit (ICU), which is particularly useful when laboratory analyses are not readily available. However, its performance in potentially septic patients with community-acquired pneumonia (CAP) needs to be examined further, especially in relation to early outcomes affecting acute management.

Objective: First, to compare the performance of qSOFA and CURB-65 in the prediction of mortality in the emergency department in patients presenting with CAP. Second, to study patients who required critical care support (CCS) and ICU admission.

Methods: Between January and December 2017, a 1-year retrospective observational study was carried out of adult (≥18 years old) patients presenting to the emergency department (ED) of our hospital (Rome, Italy) with CAP. The accuracy of qSOFA, qSOFA-65 and CURB-65 was compared in predicting mortality in the ED, CCS requirement and ICU admission. The concordance among scores ≥2 was then assessed for 30-day estimated mortality prediction.

Results: 505 patients with CAP were enrolled. Median age was 71.0 years and mortality rate in the ED was 4.7%. The areas under the curve (AUCs) of qSOFA-65, CURB-65 and qSOFA in predicting mortality rate in the ED were 0.949 (95% CI 0.873 to 0.976), 0.923 (0.867 to 0.980) and 0.909 (0.847 to 0.971), respectively. The likelihood ratio of a patient having a qSOFA score ≥2 points was higher than for qSOFA-65 or CURB-65 (11 vs 7 vs 6.7). The AUCs of qSOFA, qSOFA-65 and CURB-65 in predicting CCS requirement were 0.862 (95% CI 0.802 to 0.923), 0.824 (0.758 to 0.890) and 0.821 (0.754 to 0.888), respectively. The AUCs of qSOFA-65, qSOFA and CURB-65 in predicting ICU admission were 0.593 (95% CI 0.511 to 0.676), 0.585 (0.503 to 0.667) and 0.570 (0.488 to 0.653), respectively. The concordance between qSOFA-65 and CURB-65 in 30-day estimated mortality prediction was 93%.

Conclusion: qSOFA is a valuable score for predicting mortality in the ED and for the prompt identification of patients with CAP requiring CCS. qSOFA-65 may further improve the performance of this useful score, showing also good concordance with CURB-65 in 30-day estimated mortality prediction.
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http://dx.doi.org/10.1136/emermed-2019-208789DOI Listing
October 2020

Genetic diversity of Staphylococcus aureus influences disease phenotype of systemic lupus erythematosus.

Rheumatology (Oxford) 2021 02;60(2):958-966

Lupus Clinic, Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Rome, Italy.

Objective: We investigated the genetic diversity, molecular epidemiology and evolutionary dynamics of Staphylococcus aureus (SA) isolated from SLE patients by means of phylogenetic analysis.

Methods: Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of the translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate relationships and to assess significant clades. Selective pressure analysis was used to investigate the evolution of the SA tuf gene. The gene sequences from non-SLE individuals, downloaded from the GenBank database, were compared through phylogenetic analysis with the tuf gene from SLE patients.

Results: We enrolled 118 patients [M/F 10/108; median (interquartile range (IQR)) age 45.5 (13.2) years; median (IQR) disease duration 120 (144) months]. Twenty-four patients (20.3%) were SA carriers (SA+), three of them MRSA. SA+ SLE showed significantly higher SLEDAI-2k values [SA+: median (IQR) 2 (3.75); SA-: 0 (2); P = 0.04]. The phylogenetic analysis, restricted to 21 non-MRSA SA+, revealed a statistically supported larger clade (A, n = 17) and a smaller one (B, n = 4). Patients located in clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P < 0.0001) and SA- (62.7%, P < 0.0001). Haematological manifestations were significantly more frequent in clade A (64.7%) compared with B (50.0%, P = 0.004).

Conclusion: We suggest a possible role of SA nasal carriage status in SLE disease activity. Moreover, our findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.
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http://dx.doi.org/10.1093/rheumatology/keaa519DOI Listing
February 2021

Integration of voltammetric analysis, protein electrophoresis and pH measurement for diagnosis of pleural effusions: a non-conventional diagnostic approach.

Sci Rep 2020 09 16;10(1):15222. Epub 2020 Sep 16.

Unit of Geriatrics, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 21, 00128, Rome, Italy.

Pleural effusion is very common, but an etiologic diagnosis is often difficult. We used three unconventional diagnostic techniques (voltammetric analysis, protein electrophoresis and pH measurement) performed on pleural effusion to do a preliminary distinction between a neoplastic and a non-neoplastic origin. Pleural fluid samples were collected through thoracentesis, thoracoscopy, or post-surgery pleural drainage of 116 patients admitted to acute care wards. Samples were analyzed with the three unconventional techniques: voltammetric analysis using the BIONOTE system, capillary electrophoresis and pH measurement using a potentiometric method. The BIONOTE system is an innovative system that performs a cyclic voltammetric analysis of a biological liquid sample. The final output of the electrochemical analysis is an electrical pattern that represents a fingerprint of the analyzed sample and each sample has a different fingerprint. Data from the three unconventional diagnostic techniques were analyzed using partial least squares discriminant analysis to discriminate neoplastic from non-neoplastic effusions; we also evaluated sensitivity, specificity and percentage of correct classification. The mean age was 68 years (SD: 12); 78 (67.24%) participants were men. Results obtained from all the unconventional techniques employed showed that neoplastic and non-neoplastic pleural effusions were correctly classified in 80.2% of cases, with a sensitivity of 77% and specificity of 83%. The combined use of voltammetric analysis, protein electrophoresis and pH measurement of pleural fluid can easily and quickly distinguish a neoplastic from a non-neoplastic pleural effusion with reliable accuracy and represents an innovative diagnostic approach. In fact, this protocol can be executed in just few minutes directly in the patient's bed and it holds great promise to improve the prognosis and therapeutic chances.
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http://dx.doi.org/10.1038/s41598-020-71542-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495467PMC
September 2020

Impact of lockdown on Covid-19 case fatality rate and viral mutations spread in 7 countries in Europe and North America.

J Transl Med 2020 09 2;18(1):338. Epub 2020 Sep 2.

Institute of Human Virology, Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, USA.

Background: Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the first coronavirus disease 2019 (COVID-19) outbreak in China and has become a public health emergency of international concern. SARS-CoV-2 outbreak has been declared a pandemic by WHO on March 11th, 2020 and the same month several Countries put in place different lockdown restrictions and testing strategies in order to contain the spread of the virus.

Methods: The calculation of the Case Fatality Rate of SARS-CoV-2 in the Countries selected was made by using the data available at https://github.com/owid/covi-19-data/tree/master/public/data . Case fatality rate was calculated as the ratio between the death cases due to COVID-19, over the total number of SARS-CoV-2 reported cases 14 days before. Standard Case Fatality Rate values were normalized by the Country-specific ρ factor, i.e. the number of PCR tests/1 million inhabitants over the number of reported cases/1 million inhabitants. Case-fatality rates between Countries were compared using proportion test. Post-hoc analysis in the case of more than two groups was performed using pairwise comparison of proportions and p value was adjusted using Holm method. We also analyzed 487 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 from January 2020 to April 2020 in Italy, Spain, Germany, France, Sweden, UK and USA. SARS-CoV-2 reference genome was obtained from the GenBank database (NC_045512.2). Genomes alignment was performed using Muscle and Jalview software. We, then, calculated the Case Fatality Rate of SARS-CoV-2 in the Countries selected.

Results: In this study we analyse how different lockdown strategies and PCR testing capability adopted by Italy, France, Germany, Spain, Sweden, UK and USA have influenced the Case Fatality Rate and the viral mutations spread. We calculated case fatality rates by dividing the death number of a specific day by the number of patients with confirmed COVID-19 infection observed 14 days before and normalized by a ρ factor which takes into account the diagnostic PCR testing capability of each Country and the number of positive cases detected. We notice the stabilization of a clear pattern of mutations at sites nt241, nt3037, nt14408 and nt23403. A novel nonsynonymous SARS-CoV-2 mutation in the spike protein (nt24368) has been found in genomes sequenced in Sweden, which enacted a soft lockdown strategy.

Conclusions: Strict lockdown strategies together with a wide diagnostic PCR testing of the population were correlated with a relevant decline of the case fatality rate in different Countries. The emergence of specific patterns of mutations concomitant with the decline in case fatality rate needs further confirmation and their biological significance remains unclear.
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http://dx.doi.org/10.1186/s12967-020-02501-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463225PMC
September 2020
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