COVID-19 and tuberculosis - threats and opportunities

Impact of hepatitis C virus infection on lifestyle

AIM: To evaluate the impact of the diagnosis of hepatitis C infection on lifestyle habits such as smoking, drinking, sports activity and diet. METHODS: A self-administered, anonymous question-naire was offered to out-patients with HCV infection consecutively attending three clinical centres in Italy. RESULTS: Of the 275 respondents, 62.2% (171) were male. Mean age was 51 (range 20-80) years. Overall, after the diagnosis of hepatitis C, 74.5% of drinkers had modified (giving up or reducing) alcohol consumption, 21.3% of smokers had modified their habits and 32.3% of subjects who reported sports activity had either stopped or reduced frequency of activity or chose a less fatiguing sport. Sixt…

Optimizing patient referral and center capacity in the management of chronic hepatitis C: Lessons from the Italian experience

Abstract Aims In 2017 the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) revised the criteria for access to therapy for patients with chronic hepatitis C as part of a three-year plan to eradicate HCV. We conducted a Delphi study to determine strategies to identify and treat patients with HCV and to develop through a shared pathway, a model to manage patient referral and optimize prescription center capacity with the overall aim of increasing access to therapy. Methods The process took place in two phases – Phase I (January 2017), before the criteria for treatment of HCV were revised and Phase II (May 2017) when AIFA developed a framework for the eradication of HCV infection in Ita…

Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome

AbstractIn the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level. Host conditions and comorbidities were identified as risk factors for severe and fatal disease courses, but the mechanisms of interaction between host and SARS-CoV-2 determining the grade of COVID- 19 severity, are still unknown.We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred on published PPI, using an explorative algorithm (Random Walk with Restart) tri…

COVID-19 in people living with HIV: Clinical implications of dynamics of the immune response to SARS-CoV-2.

ABSTRACT Background Little evidence on COVID‐19 in people living with HIV (PLWH) is currently available. Material and Methods We reported clinical and viro‐immunological data of all HIV‐positive patients admitted to our centre with COVID‐19 from March 1 to May 12,2020. Results Overall, five patients were included: all were virologically‐suppressed on antiretroviral therapy and CD4+ count was >350 cell/mm3 in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. SARS‐CoV‐2‐RNA was never detected from nasopharyngeal swabs in two patients, whereas, in the others, viral clearance occurred within a maximum of 43 days. IgG prod…

COVID-19 disease - Temporal analyses of complete blood count parameters over course of illness, and relationship to patient demographics and management outcomes in survivors and non-survivors: a longitudinal descriptive cohort study

Background Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers. Methods From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribu…

Immune responses during COVID-19 infection

International audience; Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments. While protective humoral and cellular immune responses are usually m…

Mortality in COVID-19 disease patients: Correlating Association of Major histocompatibility complex (MHC) with severe acute respiratory syndrome 2 (SARS-CoV-2) variants

Highlights • In addition to ethnicity, socio-economic factors, prior vaccinations and exposure to other coronaviruses, other factors need to be considered to explain geographical and regional variations in susceptibility, severity of clinical expression of COVID-19 disease and outcomes. • Differences in peptide binding of SARS-CoV-2 variants to MHC class II, but not to MHC class I alleles frequent in individuals with African, Asian or Caucasian descent could be identified. • Single mutations in the wildtype of SARS-CoV-2, the so called B strain or L strain impact on MHC presentation • Most likely there is selective pressure from MHC class II alleles in regard to binding of the ORF8 (L84S) v…

Toning down the 2019-nCoV media hype—and restoring hope

Summary Emerging infectious diseases are an important public health threat and infections with pandemic potential are a major global risk. Although much has been learned from previous events the evidence for mitigating actions is not definitive and pandemic preparedness remains a political and scientific challenge. A need exists to develop trust and effective meaningful collaboration between countries to help with rapid detection of potential pandemic infections and initiate public health actions. This collaboration should be within the framework of the International Health Regulations. Collaboration between countries should be encouraged in a way that acknowledges the benefits that derive …

Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload

Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighte…

Chirocephalus sarpedonis sp. nov. (Branchiopoda, Anostraca, Chirocephalidae) from Turkey questions the monophyly of the traditional Chirocephalus species-groups

Chirocephalus sarpedonis sp. nov. (Anostraca, Chirocephalidae), collected in a temporary pond in Lycia (Turkey), is described and its affinities with the other species of the genus are investigated based on both morphology and mtDNA cytochrome oxidase subunit I (COI) sequences. Male and female morphology suggests its major affinity with the species belonging to the bairdi-group although the morphological peculiarities of the species make it difficult to ascribe C. sarpedonis sp. nov. to any of the Chirocephalus species-groups which are currently used in the systematics of the genus. Furthermore, molecular analyses based on the comparison with available Chirocephalus spp. COI sequences fail …

A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients

Objectives To examine whether specific T-cell-responses to SARS-CoV-2 peptides can be detected in COVID-19 using a whole-blood experimental setting, which may be further explored as potential diagnostic tool. Methods We evaluated IFN-γ levels after stimulating whole-blood with spike and remainder-antigens peptides megapools (MP) derived from SARS-CoV-2 sequences; IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, eotaxin, basic FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, VEGF were also evaluated. Results IFN-γ-response to spike and remainder-antigens MPs was significantly increased in 35 COVID-19-patients compare…

Host-directed therapies and holistic care for tuberculosis

Lessons learnt from TB screening in closed immigration centres in Italy

Background Between June 2012 and December 2013 Médecins Sans Frontières launched a pilot project with the aim of testing a strategy for improving timely diagnosis of active pulmonary TB among migrants hosted in four centres of identification and expulsion (CIE) in Italy. Methods This is a descriptive study. For active TB case finding we used an active symptom screening approach among migrants at admission in four CIE's. Here we describe the feasibility and the yield of this programme. Results Overall, 3588 migrants were screened, among whom 87 (2.4%) had a positive questionnaire. Out of 30 migrants referred for further investigations, three were diagnosed as having TB, or 0.1% out of 3588 i…

The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients

Abstract Background/objectives A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. Methods Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. Results PBMC from …

An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019

Abstract Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

Transglutaminase Type II Plays a Protective Role in Hepatic Injury

The up-regulation of "tissue" transglutaminase (TG2) gene has been shown to occur in various pathologies and can lead to severe liver injury; however, its role in the onset of liver damage has not yet been clarified. To address this issue, we have used two experimental settings: carbon tetrachloride (CCl(4))-induced liver injury in wild-type and TG2 knockout mice; and liver biopsies obtained from a large cohort of hepatitis C virus (HCV)-infected patients. Mice lacking TG2 failed to clear the hepatic necrotic tissue formed in response to prolonged CCl(4) exposure (5 weeks) and 60% of them died before the end of the treatment. By contrast, wild-type mice were able to recover after the toxic …

Orbital variations in planktonic foraminifera assemblages from the Ionian Sea during the Middle Pleistocene Transition

Abstract The Middle Pleistocene Transition (1.2–0.7 Ma) is the most recent re-organization of the global climate system which includes variations in the frequency and amplitude of glacial/interglacial cycles, increased ice sheet volume, sea surface temperature cooling and a significant drop in the CO 2 atmospheric levels. Here we present high-resolution planktonic foraminifera data (mean sampling resolution of about 780 years) from core LC10 recovered in the Ionian Sea (eastern Mediterranean), between 1.2 and 0.9 Ma. Selected taxa, among them G. ruber , T. quinqueloba and G. bulloides , show significant periodicities that can be associated to orbital cycles, mainly precession and obliquity.…

GRAd-COV2, a gorilla adenovirus-based candidate vaccine against COVID-19, is safe and immunogenic in younger and older adults

International audience; Safe and effective vaccines against coronavirus disease 2019 (COVID-19) are essential for ending the ongoing pandemic. Although impressive progress has been made with several COVID-19 vaccines already approved, it is clear that those developed so far cannot meet the global vaccine demand alone. We describe a COVID-19 vaccine based on a replication-defective gorilla adenovirus expressing the stabilized prefusion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein named GRAd-COV2. We assessed the safety and immunogenicity of a single-dose regimen of this vaccine in healthy younger and older adults to select the appropriate dose for each age group…

HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin

Abstract Background/Aims HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN α2b or STD-IFN α2b plus RBV. Methods HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy ( T 1) and at follow-up ( T 18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. Results No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load d…

ISDR pattern and evolution in patients with chronic hepatitis C treated with standard or Peg-IFN plus ribavirin

The aim of the study was to characterize the interferon sensitivity determining region (ISDR) mutation pattern and its changes at 4 weeks of treatment in a population of patients infected with hepatitis C virus (HCV) genotype 1b receiving standard or PEG-IFN plus ribavirin (RBV), to find possible early correlates of therapy outcome.Forty-five patients with chronic hepatitis due to HCV 1b were treated by PEG-IFN-α2b (n=23) or IFN-α2b (n=22) plus RBV 1000–1200 mg/day. They were classified 24 weeks after stopping therapy as sustained responders (SR), relapsers (REL) or non-responders (NR). Sixteen patients were SR, 12 REL and 17 NR. ISDR mutations were evaluated by direct sequencing at baselin…

Commemorating World TB Day 2020: “IT’S TIME” — It’s time to End the Global TB Epidemic

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to…

COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

AbstractBackgroundEpidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information.MethodsWe investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-hos…

Lessons from the COVID-19 Pandemic—Unique Opportunities for Unifying, Revamping and Reshaping Epidemic Preparedness of Europe’s Public Health Systems

GRAd-COV2, a gorilla adenovirus based candidate vaccine against COVID-19, is safe and immunogenic in young and older adults

AbstractSafe and effective vaccines against coronavirus disease 2019 (COVID-19) are urgently needed to control the ongoing pandemic. Although impressive progress has been made with several COVID-19 vaccines already approved, it is clear that those developed so far cannot meet the global vaccine demand. We have developed a COVID-19 vaccine based on a replication-defective gorilla adenovirus expressing the stabilized pre-fusion SARS-CoV-2 Spike protein, named GRAd-COV2. We aimed to assess the safety and immunogenicity of a single-dose regimen of this vaccine in healthy younger and older adults to select the appropriate dose for each age group. To this purpose, a phase 1, dose-escalation, open…

Autophagy

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide…

Additional file 2 of COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

Additional file 2: Figure S1. Pairwise distances along 259 full length CoV genomes. In the bottom of picture, indicative gene positioning along CoVs genomes is reported. The list of all considered genomes is reported in Additional file 1: Table S1. Figure S2. 3D structure of S-glycoprotein of SARS-CoV-2 and comparison with the ortholog from HCoV-229E, SARS-CoV, and MERS-CoV. Lateral (a) and superior (b) representation of SARS-CoV-2 S-glycoprotein, deducted for the sequence of patient INMI1 (MT066156.1). Each subunit chain has a different color. Structure comparison of S-glycoprotein subunit between: HCoV-229E and SARS-CoV-2, in purple and blue respectively (c); SARS-CoV and SARS-CoV-2, in r…

Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases

Abstract Background SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focussed on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. We have studied the individual response to SARS-CoV-2 of asympromatic, mild and severe COVID-19 patients in order to investigate the role of innnate and adaptive immunity in determining the clinical course after first infection. Methods To understand the basis of th…

Additional file 1 of COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

Additional file 1: Table S1. List of accession numbers of H-CoV. Table S2. List of genes selected by RWR algorithm for HCoV-229E, along with proximity score. Table S3. List of genes selected by RWR algorithm for SARS-CoV, along with proximity score. Table S4. List of genes selected by RWR algorithm for MERS-CoV, along with proximity score.