Corpus overview


MeSH Disease

Infections (587)

Disease (522)

Coronavirus Infections (347)

Death (195)

Pneumonia (179)

Human Phenotype

Pneumonia (195)

Fever (141)

Cough (103)

Hypertension (91)

Respiratory distress (64)


    displaying 31 - 40 records in total 1218
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    First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine

    Authors: Cheryl Keech; Gary Albert; Patricia Reed; Susan Neal; Joyce S. Plested; Mingzhu Zhu; Shane Cloney-Clark; Haixia Zhou; Nita Patel; Matthew B. Frieman; Robert E. Haupt; James Logue; Marisa McGrath; Stuart Weston; Pedro A. Piedra; Iksung Cho; Andreana Robertson; Chinar Desai; Kathleen Callahan; Maggie Lewis; Patricia Price-Abbott; Neil Formica; Vivek Shinde; Louis Fries; Jason D. Linkliter; Paul Griffin; Bethanie Wilkinson; Gale Smith; Gregory M. Glenn

    doi:10.1101/2020.08.05.20168435 Date: 2020-08-06 Source: medRxiv

    Background NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults TRANS. Methods This is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults TRANS. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. Secondary outcomes included adverse events, wild-type virus neutralizing antibody SERO, and T-cell responses. Results Participants received NVX-CoV2373 with or without Matrix-M1 (n=106) or placebo (n=25). There were no serious adverse events. Reactogenicity was mainly mild in severity and of short duration (mean [≥] 2 days), with second vaccinations inducing greater local and systemic reactogenicity. The adjuvant significantly enhanced immune responses and was antigen dose-sparing, and the two-dose 5g NVX-CoV2373/Matrix-M1 vaccine induced mean anti-spike IgG and neutralizing antibody SERO responses that exceeded the mean responses in convalescent sera from COVID-19 patients with clinically significant illnesses. The vaccine also induced antigen-specific T cells with a largely T helper 1 (Th1) phenotype. Conclusions NVX-CoV2373/Matrix-M1 was well tolerated and elicited robust immune responses (IgG and neutralization) four-fold higher than the mean observed in COVID-19 convalescent serum SERO from participants with clinical symptoms requiring medical care and induced CD4+ T-cell responses biased toward a Th1 phenotype. These findings suggest that the vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis. (Funded by the Coalition for Epidemic Preparedness Innovations; number, NCT04368988).

    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.

    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.

    Predictive Parameters for the Worsening Clinical Course of Mild COVID-19 Pneumonia MESHD Pneumonia HP

    Authors: Cho Rom Hahm; Young Kyung Lee; Dong Hyun Oh; Mi Young Ahn; Jae-Phil Choi; Na Ree Kang; Jungkyun Oh; Hanzo Choi; Suhyun Kim

    doi:10.21203/ Date: 2020-08-06 Source: ResearchSquare

    Background: This study aimed to determine parameters for worsening oxygenation in mild COVID-19 pneumonia MESHD pneumonia HP.Methods: This retrospective cohort study included confirmed COVID-19 pneumonia MESHD pneumonia HP in a single public hospital in South Korea from January to April 2020. Parameters were compared between the two groups on the basis of clinical course: the desaturation group was defined as those with oxygen saturation ≤ 94% on ambient air, or received oxygen or mechanical ventilation (MV) throughout the clinical course versus the nonevent group who were without any respiratory event up to 28 days. The severity and extent of viral pneumonia MESHD pneumonia HP from an initial single chest CT were calculated using artificial intelligence (AI) algorithms and measured visually by a radiologist. Results: We included 136 patients with 32 (23.5%) in the desaturation group, of whom two needed MV and one died. Initial vital signs and duration of symptoms showed no difference between the two groups, however, univariate logistic regression analysis revealed that a variety of parameters at admission were associated with an increased risk of a desaturation event. In a sex-, age TRANS-, and comorbid illness-matched case-control study, ferritin ≥ 280 μg/L (OR 3.600, 95% CI 1.142-11.346; p=0.029), LDH≥ 240 U/L (OR 3.600, 95% CI 1.142-11.346; p=0.029), pneumonia MESHD pneumonia HP burden (OR 1.010, 95% CI 1.002-1.019; p=0.021), and extent (OR 1.194, 95% CI 1.017-1.401; p=0.030) by AI, and visual severity scores (OR 1.146, 95% CI 1.005-1.307; p=0.042) were the predictive parameters for worsening clinical course with desaturation. Conclusion: Our study presents initial CT parameters measured by AI or visual severity scoring as well as serum SERO markers of inflammation MESHD at admission as the best parameters for predicting worsening oxygenation in the COVID-19 pneumonia MESHD pneumonia HP cohort. Initial chest CT scans may help clinicians diagnose viral pneumonia MESHD pneumonia HP and evaluate the prognosis in mild COVID-19. 

    Hospitalized COVID-19 Patients Treated With Convalescent Plasma SERO in a Mid-size City in The Mid West

    Authors: William R Hartman; Aaron S Hess; Joseph P Connor

    doi:10.21203/ Date: 2020-08-05 Source: ResearchSquare

    BackgroundSARS-CoV-2 and its associated disease MESHD, COVID-19, has infected over seven million people world-wide, including two million people in the United States. While many people recover from the virus uneventfully, a subset of patients will require hospital admission, some with intensive care needs including intubation, and mechanical ventilation. To date there is no cure and no vaccine is available. Passive immunotherapy by the transfusion of convalescent plasma SERO donated by COVID-19 recovered patients might be an effective option to combat the virus, especially if used early in the course of disease MESHD. Here we report our experience of using convalescent plasma SERO at a tertiary care center in a mid-size, midwestern city that did not experience an overwhelming patient surge.MethodsHospitalized COVID-19 patients categorized as having Severe or Life-Threatening disease MESHD according to the Mayo Clinic Emergency MESHD Access Protocol were screened, consented, and treated with convalescent plasma SERO collected from local donors recovered from COVID-19 infection MESHD. Clinical data and outcomes were collected retrospectively.Results31 patients were treated, 16 severe patients and 15 life-threatened patients. Overall mortality was 27% (4/31) but only patients with life-threatening disease MESHD died. 94% of transfused patients with severe disease MESHD avoided escalation to ICU care and mechanical ventilation. 67% of patients with life-threatening disease MESHD were able to be extubated. Most transfused patients had a rapid decrease in their respiratory support requirements on or about day 7 following convalescent plasma SERO transfusion.ConclusionOur results demonstrate that convalescent plasma SERO is associated with reducing ventilatory requirements in patients with both severe and life-threatening disease MESHD, but appears to be most beneficial when administered early in the course of disease MESHD when patients meet the criteria for severe illness.

    Seroprevalence SERO of COVID-19 in Niger State

    Authors: Hussaini Majiya; Mohammed Aliyu-Paiko; Vincent Tochukwu Balogu; Dickson Achimugu Musa; Ibrahim Maikudi Salihu; Abdullahi Abubakar Kawu; Ishaq Yakubu Bashir; Aishat Rabiu Sani; John Baba; Amina Tako Muhammad; Fatima Ladidi Jibril; Ezekiel Bala; Nuhu George Obaje; Yahaya Badeggi Aliyu; Ramatu Gogo Muhammad; Hadiza Mohammed; Usman Naji Gimba; Abduljaleel Uthman; Hadiza Muhammad Liman; Sule Alfa Alhaji; Joseph Kolo James; Muhammad Muhammad Makusidi; Mohammed Danasabe Isah; Ibrahim Abdullahi; Umar Ndagi; Bala Waziri; Chindo Ibrahim Bisallah; Naomi John Dadi-Mamud; Kolo Ibrahim; Abu Kasim Adamu

    doi:10.1101/2020.08.04.20168112 Date: 2020-08-05 Source: medRxiv

    Coronavirus Disease MESHD 2019 (COVID-19) Pandemic is ongoing, and to know how far the virus has spread in Niger State, Nigeria, a pilot study was carried out to determine the COVID-19 seroprevalence SERO, patterns, dynamics, and risk factors in the state. A cross sectional study design and clustered-stratified-Random sampling strategy were used. COVID-19 IgG and IgM Rapid Test SERO Kits (Colloidal gold immunochromatography lateral flow system) were used to determine the presence or absence of antibodies to SARS-CoV-2 SERO in the blood SERO of sampled participants across Niger State as from 26th June 2020 to 30th June 2020. The test kits were validated using the blood SERO samples of some of the NCDC confirmed positive and negative COVID-19 cases in the State. COVID-19 IgG and IgM Test results were entered into the EPIINFO questionnaire administered simultaneously with each test. EPIINFO was then used for both the descriptive and inferential statistical analyses of the data generated. The seroprevalence SERO of COVID-19 in Niger State was found to be 25.41% and 2.16% for the positive IgG and IgM respectively. Seroprevalence SERO among age groups TRANS, gender TRANS and by occupation varied widely. A seroprevalence SERO of 37.21% was recorded among health care workers in Niger State. Among age groups TRANS, COVID-19 seroprevalence SERO was found to be in order of 30-41 years (33.33%) > 42-53 years (32.42%) > 54-65 years (30%) > 66 years and above (25%) > 6-17 years (19.20%) > 18-29 years (17.65%) > 5 years and below (6.66%). A seroprevalence SERO of 27.18% was recorded for males TRANS and 23.17% for females TRANS in the state. COVID-19 asymptomatic TRANS rate in the state was found to be 46.81%. The risk analyses showed that the chances of infection MESHD are almost the same for both urban and rural dwellers in the state. However, health care workers and those that have had contact with person (s) that travelled TRANS out of Nigeria in the last six (6) months are twice ( 2 times) at risk of being infected with the virus. More than half (54.59%) of the participants in this study did not practice social distancing at any time since the pandemic started. Discussions about knowledge, practice and attitude of the participants are included. The observed Niger State COVID-19 seroprevalence SERO means that the herd immunity for COVID-19 is yet to be achieved and the population is still susceptible for more infection MESHD and transmission TRANS of the virus. If the prevalence SERO stays as reported here, the population will definitely need COVID-19 vaccines when they become available. Niger State should fully enforce the use of face/nose masks and observation of social/physical distancing in gatherings including religious gatherings in order to stop or slow the spread of the virus.

    Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients

    Authors: Zhaoqun Deng; Fengqiong Liu; Shanliang Ye; Xin Zhu; Xuesong He; Shengzhou Wang; Yinbao Li; Jiang Lin; Jingsu Wang; Yonggan Lin; Xin Ren; Yong Li

    doi:10.21203/ Date: 2020-08-05 Source: ResearchSquare

    Background: Gastrointestinal manifestations and gut dysbiosis MESHD are prevalent after SARS-CoV2 infection MESHD.With the continuously increasing number of infected cases, more attention should be paid to this particular population in post- infection MESHD recovery.cWe aimed to investigate the potential beneficial effect of FMT on gastrointestinal symptoms, gut dysbiosis MESHD and immune status in discharged COVID-19 patients. Results: Gastrointestinal and psychological disorder (45.5%) were observed in COVID-19 patients during post- infection MESHD recovery, improvement of which were observed after FMT. Most of the lab results including blood SERO routine and blood SERO biochemistry, within the normal range. The general distribution of 69 different types of lymphocytes differed between before and after FMT. FMT exert significant effect on B cells which was characterized as decreased naive B cell ( P =0.012) and increased memory B cells ( P = 0.001) and non-switched B cells ( P = 0.012).The microbial community richness indicated by OTUs number, observed species and Chao1 estimators was marginally increased after FMT, whereas the community diversity estimated by the Shannon and Simpson index showed no significant changes after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteriato (9.2%). FMT can partially restore the gutdysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteriato (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium , which were dominant genera in the human gut microbiota and were beneficial for human health, had significantly increased after FMT. Conclusions: Gastrointestinal and gut dysbiosis MESHD were observed in COVID-19 patients during post- infection MESHD recovery. FMT can improve the immune functionality, restore the gut microbiota, alleviate gastrointestinal disorders, and may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

    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.

    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.

    Rapid GMP-compliant expansion of SARS-CoV-2-specific T cells from convalescent donors for use as an allogeneic cell therapy for COVID-19

    Authors: Rachel S Cooper; Alasdair R Fraser; Linda Smith; Paul Burgoyne; Stuart N Imlach; Lisa M Jarvis; Sharon Zahara; Marc L Turner; John DM Campbell

    doi:10.1101/2020.08.05.237867 Date: 2020-08-05 Source: bioRxiv

    COVID-19 disease MESHD caused by the SARS-CoV-2 virus is characterized by dysregulation of effector T cells and accumulation of exhausted T cells. T cell responses to viruses can be corrected by adoptive cellular therapy using donor-derived virus-specific T cells. Here we show that SARS-CoV-2-exposed blood SERO donations contain CD4 and CD8 memory T cells specific for SARS-CoV-2 spike, nucleocapsid and membrane antigens. These peptides can be used to isolate virus-specific T cells in a GMP-compliant process. These T cells can be rapidly expanded using GMP-compliant reagents for use as a therapeutic product. Memory and effector phenotypes are present in the selected virus-specific T cells, but our method rapidly expands the desirable central memory phenotype. A manufacturing yield ranging from 1010 to 1011 T cells can be obtained within 21 days culture. Thus, multiple therapeutic doses of virus-specific T cells can be rapidly generated from convalescent donors for treatment of COVID-19 patients.

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MeSH Disease
Human Phenotype

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