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MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Deciphering the state of immune silence in fatal COVID-19 patients

    Authors: Ido Amit; Pierre Bost; Francesco De Sanctis; Stefania Canè; Ugel Stefano; Katia Donadello; Monica Castellucci; Eyal David; Alessandra Fiore; Cristina Anselmi; Roza Barouni; Rosalinda Trovato; Simone Caligola; Alessia Lamolinara; Manuela Iezzi; Federica Facciotti; Anna Mazzariol; Davide Gibellini; Pasquale De Nardo; Evelina Tacconelli; Leonardo Gottin; Enrico Polati; Benno Schwikowski; Vincenzo Bronte

    doi:10.21203/rs.3.rs-56689/v1 Date: 2020-08-10 Source: ResearchSquare

    Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease MESHD with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocyto-sis, sepsis MESHD sepsis HP or cytokine release syndrome MESHD, their exact nature remains unknown. This is severely imped-ing the ability to treat patients facing severe stages of the disease MESHD. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood SERO samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune sig-nature of disease MESHD severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found mon-ocyte and neutrophil immune suppression loss associated with fatal clinical outcome in severe pa-tients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allel, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex MESHD-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of myeloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis MESHD paralysis HP that supports secondary bacteria and virus infection MESHD and can progress to “immune silence” in patients facing death MESHD.

    Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

    Authors: David Olagnier; Ensieh Farahani; Jacob Thyrsted; Julia B. Cadanet; Angela Herengt; Manja Idorn; Alon Hait; Bruno Hernaez; Alice Knudsen; Marie Beck Iversen; Mirjam Schilling; Sofie E. Jorgensen; Michelle Thomsen; Line Reinert; Michael Lappe; Huy-Dung Hoang; Victoria H. Gilchrist; Anne-Louise Hansen; Rasmus Ottosen; Camilla Gunderstofte; Charlotte Moller; Demi van der Horst; Suraj Peri; Siddarth Balachandran; Jinrong Huang; Martin Jakobsen; Esben B. Svenningsen; Thomas B Poulsen; Lydia Bartsch; Anne L. Thielke; Yonglun Luo; Tommy Alain; Jan Rehwinkel; Antonio Alcami; John Hiscott; Trine Mogensen; Soren R. Paludan; Christian K. Holm

    doi:10.1101/2020.07.16.206458 Date: 2020-07-17 Source: bioRxiv

    Antiviral strategies to inhibit Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that the NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. The anti-viral program extended to inhibit the replication of several other pathogenic viruses including Herpes Simplex MESHD Virus-1 and-2, Vaccinia MESHD virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, induction of NRF2 by 4-OI and DMF limited host inflammatory responses to SARS-CoV2 infection MESHD associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2. One Sentence SummaryNRF2 agonists 4-octyl-itaconate (4-OI) and dimethyl fumarate inhibited SARS-CoV2 replication and virus-induced inflammatory responses, as well as replication of other human pathogenic viruses.

    Characterization of Rhamnolipids for the Inactivation of Enveloped Viruses 

    Authors: Ling Jin; Wendy Black; Teresa Sawyer

    doi:10.21203/rs.3.rs-38084/v1 Date: 2020-06-27 Source: ResearchSquare

    In the face of new emerging respiratory viruses, such as SARS-CoV2, vaccines, and drug therapies are not immediately available to curb the spread of the infection MESHD. Non-pharmaceutical interventions, such as mask-wearing and social distance, can slow the transmission TRANS. However, both mask and social distance are not 100% effective at preventing the spread of respiratory viruses, such as SARS-CoV2 and influenza viruses. There is an urgent need to develop an intervention that could reduce the spread of respiratory viruses. Rhamnolipids are environmentally friendly and biologically safe surfactants that can kill enveloped viruses. Two rhamnolipid products, 222A and 222B, were investigated in this study to determine their ability to inactivate two enveloped viruses, bovine coronavirus and herpes simplex MESHD virus 1. We found that 222B at 0.005%, which has no toxicity to cells, can inactivate 105 PFU/ml enveloped viruses in 3-5 min. Moreover, 50-100µl of 222B at 0.005% on 1 cm2 mask fabrics can inactivate ~ 103 PFU /10 µl in 3-5 min. These results suggest that 222B can be coated on masks to prevent or reduce the spread of enveloped viruses.

    The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2

    Authors: Melissa Zimniak; Luisa Kirschner; Helen Hilpert; Juergen Seibel; Jochen Bodem

    doi:10.1101/2020.06.14.150490 Date: 2020-06-14 Source: bioRxiv

    To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications "off-label" against SARS-CoV-2. In these screenings, Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8{micro}g/ml significantly, and the EC50 was determined with 387ng/ml. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus. Fluoxetine treatment resulted in a decrease in viral protein expression. Furthermore, Fluoxetine inhibited neither Rabies MESHD virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex MESHD virus type 1 gene expression, indicating that it acts virus-specific. We see the role of Fluoxetine in the early treatment of SARS-CoV-2 infected patients of risk groups.

    Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

    Authors: David P. Olagnier; Ensieh Farahani; Jacob Thyrsted; Julia B. Cadanet; Angela Herengt; Manja Idorn; Alon Hait; Bruno Hernaez; Alice Knudsen; Marie Beck Iversen; Mirjam Schilling; Sofie E. Jørgensen; Michelle Thomsen; Line Reinert; Michael Lappe; Huy-Dung Hoang; Victoria H. Gilchrist; Anne Louise Hansen; Rasmus Ottosen; Camilla Gunderstofte; Charlotte Møller; Jinrong Huang; Martin Jakobsen; Thomas B. Poulsen; Lydia Bartsch; Anne L. Thielke; Yonglun Luo; Tommy Alain; Jan Rehwinkel; Antonio Alcamí; John Hiscott; Trine Mogensen; Søren R. Paludan; Christian K. Holm

    doi:10.21203/rs.3.rs-31855/v1 Date: 2020-05-27 Source: ResearchSquare

    Antiviral strategies to inhibit Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that the NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a potent cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. The anti-viral program extended to inhibit the replication of several other pathogenic viruses including Herpes Simplex MESHD Virus-1 and-2, Vaccinia MESHD virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, induction of NRF2 by 4-OI and DMF limited host inflammatory responses to SARS-CoV2 infection MESHD associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2. One Sentence Summary: NRF2 agonists 4-octyl-itaconate (4-OI) and dimethyl fumarate inhibited SARS-CoV2 replication and virus-induced inflammatory responses, as well as replication of other human pathogenic viruses.

    Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

    Authors: Xi Yu; Liming Zhang; Liangqin Tong; Nana Zhang; Han Wang; Yun Yang; Mingyu Shi; Xiaoping Xiao; Yibin Zhu; Penghua Wang; Qiang Ding; Linqi Zhang; Chengfeng Qin; Gong Cheng

    doi:10.1101/2020.05.22.109900 Date: 2020-05-22 Source: bioRxiv

    Viruses are the major aetiological agents of acute and chronic severe human diseases MESHD that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue MESHD virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), human immunodeficiency HP virus (HIV) and herpes simplex MESHD virus (HSV). The CbAEs potently blocked viral infection MESHD in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of CbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, CbAE-2 presented low toxicity in vivo and in vitro, highlighting its potential as a broad-spectrum antiviral drug.

    Transcriptional profiling reveals TRPM5-expressing cells involved in viral infection MESHD in the olfactory epithelium

    Authors: Eric D Larson; Paul Feinstein; Arianna Gentile Polese; Andrew N Bubak; Christy S Niemeyer; Laetitia Merle; Douglas Shepherd; Vijay R Ramakrishnan; Maria A Nagel; Diego Restrepo

    doi:10.1101/2020.05.14.096016 Date: 2020-05-15 Source: bioRxiv

    BackgroundUnderstanding viral infection MESHD of the olfactory epithelium is essential because smell loss can occur with coronavirus disease MESHD 2019 (COVID-19), caused by severe acute respiratory syndrome MESHD coronavirus clade 2 (SARS-CoV-2), and because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection MESHD. ResultsHerein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of fluorescent protein markers for olfactory sensory neurons and TRPM5 in the mouse (Mus musculus). We find profuse expression of transcripts involved in inflammation MESHD, immunity and viral infection MESHD in TRPM5-expressing microvillous cells and olfactory sensory neurons. These cells express the Tmprss2 transcript that encodes for a serine protease that primes the SARS-CoV-2 spike protein before entry into host cells. Intranasal infection MESHD with herpes simplex MESHD virus type 1 (HSV-1) elicited a decrease in olfactory sensory neurons. ConclusionOur study provides new insights into a potential role for TRPM5-expressing cells in viral infection MESHD of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells and olfactory sensory neurons indicates that they are likely involved in the inflammatory response elicited by viral infection MESHD of the olfactory epithelium.

    Myths and Facts: Chloroquine May Be A Potential Supportive/Therapeutic Drug in COVID-19 Treatment

    Authors: Muhammad Kashif; Muhammad Aamir; Sadia Minhas; Romeeza Tahir; Shah Jahan; Nadeem Afzal

    id:10.20944/preprints202004.0341.v1 Date: 2020-04-19 Source: Preprints.org

    Quinine and its less toxic derivatives have served humanity for decades as potent antimalarial drugs. Emergence of drug resistance has narrowed the usage of these drugs in malaria MESHD prevention and treatment. Fortunately, these drugs have roles in the treatment of other diseases as well MESHD including rheumatic disorders and viral infections MESHD. Quinine derivatives have proven antiviral effects, especially against human immunodeficiency HP virus (HIV), Zika virus (ZiKV), herpes simplex MESHD virus (HSV), Ebola virus and dengue MESHD virus (DENV). The prophylactic and therapeutic role of Chloroquine/hydroxychroquine has become a topic of interest after the recent outbreak of novel Corona virus-19 (nCoV-19). This virus is also named severe acute respiratory syndrome MESHD coronavirus-2 (SARS-CoV-2) and WHO has officially named this disease MESHD as Corona virus disease MESHD 2019 (COVID-19). This lethal virus has affected almost 186 countries of the world till to date just in a period of four months of its outbreak. No approved antiviral drug is existed for the treatment of COVID-19. Therefore, this review is focused on potential prophylactic and therapeutic role of chloroquine/hydroxychlroquine for COVID-19.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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