Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 632
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    Antibody SERO Response and Therapy in COVID-19 Patients: Significance in Vaccine Development

    Authors: Ligong Lu; Hui Zhang; Meixiao Zhan; Jun Jiang; Hua Yin; Danielle J. Dauphars; Shi-You Li; Yong Li; You-Wen He

    id:10.20944/preprints202008.0166.v1 Date: 2020-08-06 Source:

    The newly emerged severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease MESHD 2019 (COVID-19) due to SARS-CoV-2 infection MESHD is lacking and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection MESHD is a critical determinant for patients’ outcome. SARS-CoV-2 infection MESHD results in seroconversion and production of anti- SARS-CoV-2 antibodies SERO. The antibodies SERO may suppress viral replication through neutralization but also might also participate in COVID-19 pathogenesis through a process termed antibody SERO-dependent enhancement. Rapid progress has been made in the research of antibody SERO response and therapy in COVID-19 patients including characterization of the clinical features of antibody SERO responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma SERO and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies SERO, as well as preliminary clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

    Signatures and mechanisms of efficacious therapeutic ribonucleotides against SARS-CoV-2 revealed by analysis of its replicase using magnetic tweezers

    Authors: Mona Seifert; Subhas C. Bera; Pauline van Nies; Robert N. Kirchdoerfer; Ashleigh Shannon; Thi-Tuyet-Nhung Le; Tyler L. Grove; Flavia S. Papini; Jamie J. Arnold; Steven C. Almo; Bruno Canard; Martin Depken; Craig E. Cameron; David Dulin

    doi:10.1101/2020.08.06.240325 Date: 2020-08-06 Source: bioRxiv

    Coronavirus Disease MESHD 2019 (COVID-19) results from an infection MESHD infection by the severe HP by the severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), the third coronavirus outbreak to plague MESHD humanity this century. Currently, the most efficacious therapeutic against SARS-CoV-2 infection MESHD is the Remdesivir (RDV), an adenine-like ribonucleotide analogue that is very efficiently incorporated by the SARS-CoV-2 replicase. Understanding why RDV is so well incorporated will facilitate development of even more effective therapeutics. Here, we have applied a high-throughput, single-molecule, magnetic-tweezers platform to study thousands of cycles of nucleotide addition by the SARS-CoV-2 replicase in the absence and presence of RDV, a Favipiravir-related analog (T-1106), and the endogenously produced ddhCTP. Our data are consistent with two parallel catalytic pathways of the replicase: a high-fidelity catalytic (HFC) state and a low-fidelity catalytic (LFC) state, the latter allowing the slow incorporation of both cognate and non-cognate nucleotides. ddhCTP accesses HFC, T-1106 accesses LFC as a non-cognate nucleotide, while RDV efficiently accesses both LFC pathway. In contrast to previous reports, we provide unequivocal evidence against RDV functioning as a chain terminator. We show that RDV incorporation transiently stalls the replicase, only appearing as termination events when traditional, gel-based assays are used. The efficiency of ddhCTP utilization by the SARS-CoV-2 replicase suggests suppression of its synthesis during infection MESHD, inspiring new therapeutic strategies. Use of this experimental paradigm will be essential to the development of therapeutic nucleotide analogs targeting polymerases.

    Prediction of Single Point Mutations in Ganglioside-Binding Domain of SARS-CoV-2 S and Their Effects on Binding of 9-O-Acetylated Sialic Acid and Hidroxychloroquine

    Authors: Petar M. Mitrasinovic

    doi:10.26434/chemrxiv.12765953.v1 Date: 2020-08-06 Source: ChemRxiv

    The infectious disease MESHD CoViD-19 is caused by a new severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), also referred to as hCoV-19. A possible infection MESHD mechanism includes dual host receptor recognitions by the SARS-CoV-2 transmembrane spike (S) glycoproteins. SARS-CoV-2 S contains two different domains, the receptor-binding domain (RBD) and the N-terminal domain (NTD), which interact with the angiotensin-converting enzyme 2 (ACE2) and the ganglioside-rich domain of the plasma SERO membrane at the surface of respiratory cell, respectively. The NTD amino acid residues (111-162) form a functional ganglioside-binding domain (GBD) that is conserved in all clinical isolates. Herein, the single point mutations (SPMs) of the GBD residues to which the virus is prone during genetic adaptation are predicted using an in silico protein engineering approach. Consequently, their effects on the attachment of SARS-CoV-2 S to the ganglioside-linked 9-O-acetylated sialic acid (9-O-Ac-Sia) are explored using molecular docking simulations. Val120Tyr and Asn122Trp are found to be the most likely SPMs in the GBD of SARS-CoV-2 S being involved in very specific recognition with 9-O-Ac-Sia through electrostatic interactions. Val120Tyr and Asn122Trp are also found to be the most likely SPMs in the GBD of SARS-CoV-2 S that is involved in conspicuously hydrophobic recognition with hidroxychloroquine (Hcq), thereby indicating the ability of Hcq to competitively inhibit GBD interactions with lipid rafts. However, the considerably non-specific binding of Hcq and the micromolar range of the dissociation constants of the SARS-CoV-2 S/Hcq complexes do not support the proposal of treating Hcq as a drug candidate. Maintaining a clear resemblance of the structure of a potential drug candidate to a natural substrate, accompanied by essential functional group modifications, may be a usable guideline for the structure-based design of anti-CoViD-19 drugs.

    Serology assessment of antibody SERO response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test SERO

    Authors: Yang De Marinis; Torgny Sunnerhagen; Pradeep Bompada; Anna Blackberg; Runtao Yang; Joel Svensson; Ola Ekstrom; Karl-Fredrik Eriksson; Ola Hansson; Leif Groop; Isabel Goncalves; Magnus Rasmussen

    doi:10.1101/2020.08.05.20168815 Date: 2020-08-06 Source: medRxiv

    The coronavirus disease MESHD 2019 (COVID-19) pandemic has created a global health- and economic crisis. Lifting confinement restriction and resuming to normality depends greatly on COVID-19 immunity screening. Detection of antibodies SERO to severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection MESHD. In this study, we applied a rapid COVID-19 IgM/IgG antibody test SERO and performed serology assessment of antibody SERO response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n=45), the total antibody SERO detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. We also studied antibody SERO response in relation to time after symptom onset TRANS and disease MESHD severity, and observed an increase in antibody SERO reactivity and distinct distribution patterns of IgM and IgG following disease progression MESHD. The total IgM and IgG detection is 63% in patients with < 2 weeks from disease MESHD onset; 85% in non-hospitalized patients with > 2 weeks disease MESHD duration; and 91% in hospitalized patients with > 2 weeks disease MESHD duration. We also compared different blood SERO sample types and suggest a potentially higher sensitivity SERO by serum SERO/ plasma SERO comparing with whole blood SERO measurement. To study the specificity of the test, we used 69 sera/ plasma SERO samples collected between 2016-2018 prior to the COVID-19 pandemic, and obtained a test specificity of 97%. In summary, our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody SERO detection patterns in association with disease MESHD progress and hospitalization. Our study supports that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.

    Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

    Authors: Markus Hoffmann; Heike Hofmann-Winkler; Joan C. Smith; Nadine Krueger; Lambert K. Sorensen; Ole S. Sogaard; Jorgen Bo Hasselstrom; Michael Winkler; Tim Hempel; Lluis Raich; Simon Olsson; Takashi Yamazoe; Katsura Yamatsuta; Hirotaka Mizuno; Stephan Ludwig; Frank Noe; Jason M. Sheltzer; Mads Kjolby; Stefan Poehlmann

    doi:10.1101/2020.08.05.237651 Date: 2020-08-05 Source: bioRxiv

    Antiviral therapy is urgently needed to combat the coronavirus disease MESHD 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The protease inhibitor camostat mesylate inhibits SARS-CoV-2 infection MESHD of lung cells by blocking the virus-activating host cell protease TMPRSS2. Camostat mesylate has been approved for treatment of pancreatitis MESHD pancreatitis HP in Japan and is currently being repurposed for COVID-19 treatment. However, potential mechanisms of viral resistance as well as camostat mesylate metabolization and antiviral activity of metabolites are unclear. Here, we show that SARS-CoV-2 can employ TMPRSS2-related host cell proteases for activation and that several of them are expressed in viral target cells. However, entry mediated by these proteases was blocked by camostat mesylate. The camostat metabolite GBPA inhibited the activity of recombinant TMPRSS2 with reduced efficiency as compared to camostat mesylate and was rapidly generated in the presence of serum SERO. Importantly, the infection MESHD experiments in which camostat mesylate was identified as a SARS-CoV-2 inhibitor involved preincubation of target cells with camostat mesylate in the presence of serum SERO for 2 h and thus allowed conversion of camostat mesylate into GBPA. Indeed, when the antiviral activities of GBPA and camostat mesylate were compared in this setting, no major differences were identified. Our results indicate that use of TMPRSS2-related proteases for entry into target cells will not render SARS-CoV-2 camostat mesylate resistant. Moreover, the present and previous findings suggest that the peak concentrations of GBPA established after the clinically approved camostat mesylate dose (600 mg/day) will result in antiviral activity.

    Alveolitis in severe SARS-CoV-2 pneumonia MESHD pneumonia HP is driven by self-sustaining circuits between infected alveolar macrophages and T cells

    Authors: Rogan A Grant; Luisa Morales-Nebreda; Nikolay S Markov; Suchitra Swaminathan; Estefany R Guzman; Darryl A Abbott; Helen K Donnelly; Alvaro Donayre; Isaac A Goldberg; Zasu M Klug; Nicole Borkowski; Ziyan Lu; Hermon Kihshen; Yuliya Politanska; Lango Sichizya; Mengjia Kang; Ali Shilatifard; Chao Qi; A Christine Argento; Jacqueline M Kruser; Elizabeth S Malsin; Chiagozie O Pickens; Sean Smith; James M Walter; Anna E Pawlowski; Daniel Schneider; Prasanth Nannapaneni; Hiam Abdala-Valencia; Ankit Bharat; Cara J Gottardi; GR Scott Budinger; Alexander A Misharin; Benjamin David Singer; Richard G Wunderink; - The NU SCRIPT Study Investigators

    doi:10.1101/2020.08.05.238188 Date: 2020-08-05 Source: bioRxiv

    Some patients infected with Severe Acute Respiratory Syndrome MESHD Coronavirus-2 (SARS-CoV-2) develop severe pneumonia MESHD pneumonia HP and the acute respiratory distress HP syndrome MESHD (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia MESHD pneumonia HP. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure HP and 252 patients with known or suspected pneumonia MESHD pneumonia HP from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection MESHD at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia HP. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation MESHD.

    Comparative Evaluation of Three Serologic Assays for the Identification of SARS-CoV-2 Antibodies SERO

    Authors: Keenan O. Hogan; Dave Klippel; Fred V. Plapp; Rachael M. Liesman

    doi:10.1101/2020.08.04.20167643 Date: 2020-08-05 Source: medRxiv

    Background and aims Serologic assays for the detection of severe acute respiratory syndrome MESHD coronavirus 2 ( SARS-CoV-2) antibodies SERO are being developed and approved rapidly with limited external validation. Accurate diagnostics are an essential component to pandemic management and public health. Materials and methods Residual serum samples SERO (N=113) from patients who were evaluated for SARS-CoV-2 infection MESHD status by polymerase chain reaction (PCR) were retrospectively tested in parallel across three automated SARS-CoV-2 serologic assays: Liaison SARS-CoV-2 S1/S2 IgG, Elecsys anti-SARS-CoV-2 total antibody SERO, and Access SARS-CoV-2 IgG. Results Testing of 51 PCR-positive and 62 PCR-negative patients demonstrated qualitative inter-test agreement of 96% overall, 100% in PCR-negative patients, 88% in early positive samples (0-13 days post positive PCR), and 100% in convalescent samples (14+ days post positive PCR). Calculated kappa values for paired inter-test agreement ranged 0.93-0.96. Compared to PCR, overall percent positive agreement ranged from 82-86% (100% for convalescent samples) and percent negative agreement was 100% for each assay. Conclusion This study demonstrates high diagnostic accuracy and inter-test agreement for three automated SARS-CoV-2 serologic assays. External validation of serologic assays is critical to ensure diagnostic accuracy and appropriate utilization of critical resources.

    Face masks prevent transmission TRANS of respiratory diseases MESHD: a meta-analysis of randomized controlled trials

    Authors: Hanna M Ollila; Markku Partinen; Jukka Koskela; Riikka Savolainen; Anna Rotkirch; Liisa T Laine

    doi:10.1101/2020.07.31.20166116 Date: 2020-08-04 Source: medRxiv

    Background: Coronavirus Disease MESHD 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) and spreads through droplet-mediated transmission TRANS on contaminated surfaces and in air. Mounting scientific evidence from observational studies suggests that face masks for the general public may reduce the spread of infections MESHD. However, results from randomized control trials (RCT) have been presented as inconclusive, and concerns related to the safety and efficacy of non-surgical face masks in non-clinical settings remain. This controversy calls for a meta-analysis which considers non-compliance in RCTs, the time-lag in benefits of universal masking, and possible adverse effects. Methods: We performed a meta-analysis of RCTs of non-surgical face masks in preventing viral respiratory infections MESHD in non-hospital and non-household settings at cumulative and maximum follow-up as primary endpoints. The search for RCTs yielded five studies published before May 29th, 2020. We pooled estimates from the studies and performed random-effects meta-analysis and mixed-effects meta-regression across studies, accounting for covariates in compliance vs. non-compliance in treatment. Results: Face masks decreased infections across MESHD all studies at maximum follow-up (p=0.0318$, RR=0.608 [0.387 - 0.956]), and particularly in studies without non-compliance bias. We found significant between-study heterogeneity in studies with bias (I^2=71.2%, p=0.0077). We also used adjusted meta-regression to account for heterogeneity. The results support a significant protective effect of masking (p=0.0006, beta=0.0214, SE= 0.0062). No severe adverse effects were detected. Interpretation: The meta-analysis of existing randomized control studies found support for the efficacy of face masks among the general public. Our results show that face masks protect populations from infections MESHD and do not pose a significant risk to users. Recommendations and clear communication concerning the benefits of face masks should be provided to limit the number of COVID-19 and other respiratory infections MESHD.

    SARS-CoV-2 Infection MESHD Among Symptom-Free Healthcare Workers

    Authors: Ryan T. Demmer; Angela Ulrich; Talia Wiggen; Ali Strickland; Brianna Naumchik; Shalini Kulasingam; Steven D. Stovitz; Clarisse Marotz; Pedro Belda-Ferre; Greg Humphrey; Peter De Hoff; Louise Laurent; Susan Kline; Rob Knight

    doi:10.1101/2020.07.31.20166066 Date: 2020-08-04 Source: medRxiv

    Importance: Current evidence suggests that transmission TRANS of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) is possible among symptom-free individuals but limited data are available on this topic in healthcare workers (HCW). The quality and acceptability of self-collected nasopharyngeal swabs (NPS) is unknown. Objective: To estimate the prevalence SERO of SARS-CoV-2 infection MESHD and to assess the acceptability of self-collected NPS among HCW. Design: Cross-sectional convenience sample enrolled between April 20th and June 24th, 2020. We had >95% power to detect at least one positive test if the true underlying prevalence SERO of SARS-CoV2 was > 1%. Setting: The metropolitan area surrounding Minneapolis and St. Paul, Minnesota. Participants: HCW free of self-reported upper respiratory symptoms were recruited. Exposures: Participants completed questionnaires regarding demographics, household characteristics, personal protective equipment (PPE) utilization and comorbidities. Outcomes: A participant self-collected nasopharyngeal swab (NPS) was obtained. SARS-CoV-2 infection MESHD was assessed via polymerase chain reaction. NPS discomfort was assessed on a scale of 1 (no discomfort) - 10 (extreme discomfort). NPS duration and depth into the nasopharynx, and willingness to perform future self-collections were assessed. Results: Among n=489 participants 80% were female TRANS and mean age TRANS+/-SD was 41+/-11. Participants reported being physicians (14%), nurse practitioners (8%), physicians assistants (4%), nurses (51%), medics (3%), or other which predominantly included laboratory technicians and administrative roles (22%). Exposure to a known/suspected COVID-19 case in the 14 days prior to enrollment was reported in 40% of participants. SARS-CoV-2 was not detected in any participant. The mean+/-SD discomfort level of the NPS was 4.5+/-2.0. 95% of participants reported that their self-swab was longer than or equal to the duration of patient swabs they had previously performed, and 89% reported the depth to be deeper than or equal to the depth of previous patient swabs. Over 95% of participants reported a willingness to repeat a self-collected NP swab in the future. Conclusions and Relevance: The point prevalence SERO of SARS-CoV-2 infection MESHD was likely very low in symptom-free Minnesota healthcare workers from April 20th and June 24th, 2020. Self-collected NP swabs are well-tolerated and a viable alternative to provider-collected swabs to preserve PPE.

    Cold-adapted live attenuated SARS-CoV-2 vaccine completely protects human ACE2 transgenic mice from SARS-CoV-2 infection MESHD

    Authors: Sang Heui Seo; Yunyueng Jang

    doi:10.1101/2020.08.04.235689 Date: 2020-08-04 Source: bioRxiv

    Severe acute respiratory syndrome MESHD coronavirus (SARS-CoV-2) has infected more than 16,000,000 people and has caused the death MESHD of more than 650,000 individuals since December 2019. A safe and effective vaccine that can provide herd immunity against SARS-CoV-2 is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe the development of a cold-adapted live attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22{degrees}C/2020) by gradually adapting the growth of SARS-CoV-2 from 37{degrees}C to 22{degrees}C in Vero cells. This vaccine can be potentially administered to humans through nasal spray. Its single dose was observed to strongly induce the neutralising antibody SERO (>640), cellular immunity, and mucosal IgA antibody SERO in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infection MESHD. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection MESHD and did not show loss of body weight MESHD, death MESHD, and the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. Taken together, the cold-adapted live attenuated SARS-CoV-2 vaccine developed by us may contribute to saving of human lives from the threat of SARS-CoV-2.

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MeSH Disease
Human Phenotype

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