Corpus overview


MeSH Disease

Human Phenotype


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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.

    IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection MESHD

    Authors: Bruce A. Rosa; Mushtaq Ahmed; Dhiraj K. Singh; Jose Alberto Choreno-Parra; Journey Cole; Luis Armando Jimenez-Alvarez; Tatiana Sofia Rodriguez-Reyna; Bindu Singh; Olga Golzalez; Ricardo Carrion; Larry S. Schlesinger; John Martin; Joaquin Zuniga; Makedonka Mitreva; Shabaana A Khader; Deepak Kaushal

    doi:10.1101/2020.08.06.239798 Date: 2020-08-06 Source: bioRxiv

    The novel virus SARS-CoV-2 has infected more than 14 million people worldwide resulting in the Coronavirus disease MESHD 2019 (COVID-19). Limited information on the underlying immune mechanisms that drive disease MESHD or protection during COVID-19 severely hamper development of therapeutics and vaccines. Thus, the establishment of relevant animal models that mimic the pathobiology of the disease MESHD is urgent. Rhesus macaques infected with SARS-CoV-2 exhibit disease MESHD pathobiology similar to human COVID-19, thus serving as a relevant animal model. In the current study, we have characterized the transcriptional signatures induced in the lungs of juvenile and old rhesus macaques following SARS-CoV-2 infection MESHD. We show that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated. In COVID-19, increasing age TRANS is a significant risk factor for poor prognosis and increased mortality. We demonstrate that Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease MESHD. In contrast, pathways involving VEGF are downregulated in lungs of old infected macaques. Using samples from humans with SARS-CoV-2 infection MESHD and COVID-19, we validate a subset of our findings. Finally, neutrophil degranulation, innate immune system and IFN gamma signaling pathways are upregulated in both tuberculosis MESHD and COVID-19, two pulmonary diseases MESHD where neutrophils are associated with increased severity. Together, our transcriptomic studies have delineated disease MESHD pathways to improve our understanding of the immunopathogenesis of COVID-19 to facilitate the design of new therapeutics for COVID-19.

    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.

    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.

    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.

    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.

    Combinatorial therapeutic plan for COVID-19 treatment armed up with antiviral, antiparasitic, cell-entry inhibitor, and immune-boosters

    Authors: Nabanita Roy Chattopadhyay; Koustav Chatterjee; Antara Banerjee; Tathagata Choudhuri

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

    SARS-CoV-2, or novel coronavirus, is causing the fatal and contagious coronavirus disease MESHD-2019 (COVID-19) affecting thousands of people every single day. Researchers are continuously searching for any possible cure and/or vaccine, but no conclusive report is available till date. Like many others, we realize that a rapid, immediate, and elaborate strategy must be adopted to protect mankind. To avoid the time-loss due to clinical trials, we have tested some FDA-approved drugs to combat COVID-19. We accessed information from public databases and publications, and studied the mechanism of infection MESHD of SARS-CoV-2 and the interactions of various drugs with SARS-CoV-2 proteins in silico. We found a few antivirals and antiparasitic drugs to interact with important SARS-CoV-2 proteins. Particularly Galidesivir, Remdesivir, and Pirodavir are the chosen antiviral drugs; and Proguanil, Mefloquine, and Artesunate are the chosen antiparasitic drugs. In addition, inhibitors to prevent host-cell entry and a few supportive immuneboosters can be used in different combinations. Our study proposes a four-way attack to this fatal virus for the possible management of COVID-19 armed up with an antiviral, an antiparasitic drug, a cell-entry inhibitor, and a few supportive immune-boosters, which can be used in different combinations in different groups of people.

    Analysis of COVID-19 and comorbidity co- infection MESHD Model with Optimal Control

    Authors: Dr. Andrew Omame; Nometa Ikenna

    doi:10.1101/2020.08.04.20168013 Date: 2020-08-04 Source: medRxiv

    The new coronavirus disease MESHD 2019 (COVID-19) infection MESHD is a double challenge for people infected with comorbidities such as cardiovascular and cerebrovascular diseases MESHD and diabetes. Comorbidities have been reported to be risk factors for the complications of COVID-19. In this work, we develop and analyze a mathematical model for the dynamics of COVID-19 infection MESHD in order to assess the impacts of prior comorbidity on COVID-19 complications and COVID-19 re- infection MESHD. The model is simulated using data relevant to the dynamics of the diseases MESHD in Lagos, Nigeria, making predictions for the attainment of peak periods in the presence or absence of comorbidity. The model is shown to undergo the phenomenon of backward bifurcation caused by the parameter accounting for increased susceptibility to COVID-19 infection MESHD by comorbid susceptibles as well as the rate of re- infection MESHD by those who have recovered from a previous COVID-19 infection MESHD. Sensitivity SERO analysis of the model when the population of individuals co-infected with COVID-19 and comorbidity is used as response function revealed that the top ranked parameters that drive the dynamics of the co- infection MESHD model are the effective contact rate for COVID-19 transmission TRANS, $\beta\sst{cv}$, the parameter accounting for increased susceptibility to COVID-19 by comorbid susceptibles, $\chi\sst{cm}$, the comorbidity development rate, $\theta\sst{cm}$, the detection rate for singly infected and co-infected individuals, $\eta_1$ and $\eta_2$, as well as the recovery rate from COVID-19 for co-infected individuals, $\varphi\sst{i2}$. Simulations of the model reveal that the cumulative confirmed cases TRANS (without comorbidity) may get up to 180,000 after 200 days, if the hyper susceptibility rate of comorbid susceptibles is as high as 1.2 per day. Also, the cumulative confirmed cases TRANS (including those co-infected with comorbidity) may be as high as 1000,000 cases by the end of November, 2020 if the re- infection MESHD rates for COVID-19 is 0.1 per day. It may be worse than this if the re- infection MESHD rates increase higher. Moreover, if policies are strictly put in place to step down the probability of COVID-19 infection MESHD by comorbid susceptibles to as low as 0.4 per day and step up the detection rate for singly infected individuals to 0.7 per day, then the reproduction number TRANS can be brought very low below one, and COVID-19 infection MESHD eliminated from the population. In addition, optimal control and cost-effectiveness analysis of the model reveal that the the strategy that prevents COVID-19 infection MESHD by comorbid susceptibles has the least ICER and is the most cost-effective of all the control strategies for the prevention of COVID-19.

    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.

    Assessment of a Laboratory-Based SARS-CoV-2 Antibody SERO Test Among Hemodialysis Patients: A Quality Improvement Initiative

    Authors: Dena E Cohen; Gilbert Marlowe; Gabriel Contreras; Marie Ann Sosa; Jair Munoz Mendoza; Oliver Lenz; Zain Mithani; Pura Margarita Teixeiro; Nery Queija; Araceli Moneda; Jean S Jeanty; Katherine Swanzy; Misha Palecek; Mahesh Krishnan; Jeffery Giullian; Steven M Brunelli

    doi:10.1101/2020.08.03.20163642 Date: 2020-08-04 Source: medRxiv

    Abstract Introduction: The coronavirus disease MESHD 2019 (COVID -19) pandemic is caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS -CoV -2) infection MESHD. Although tests to detect anti - SARS -CoV-2 antibodies SERO have been developed, their sensitivity SERO and specificity in hemodialysis patients have not been previously assessed. Methods: As part of a quality improvement (QI) initiative, nasopharyngeal swabs and predialysis blood SERO samples were collected on the same day from adult TRANS patients receiving routine hemodialysis care at clinics managed by a large dialysis organization in the greater Miami, Florida region (23 - 30 Apr 2020). Polymerase chain reaction (PCR) tests for SARS -CoV -2 and chemiluminescence immunoassays SERO for anti -SARS -CoV2 antibodies SERO were performed according to manufacturer-specified protocols. Results: Of 715 participants in the QI initiative, 38 had symptomatology consistent with COVID -19 prior to or during the initiative. Among these, COVID -19 was PCR -confirmed in 14 and ruled out in 20, with the remaining 4 being inconclusive. Among the 34 patients with known COVID -19 status, the sensitivity SERO and specificity of the antibody test SERO were 57.1% and 85.0% when either antibody SERO was considered. The remaining 677 patients had no record of symptoms consistent with COVID -19, nor any known exposure. Of these, 38 patients (5.6%) tested positive for anti- SARS-CoV-2 antibodies SERO. Conclusions: The operational characteristics of the laboratory-based antibody test SERO make it sufficient to rule in, but not rule out, SARS -CoV -2 infection MESHD in the appropriate clinical circumstance. A substantial proportion of dialysis patients may have had asymptomatic TRANS SARS -CoV -2 infection MESHD.

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MeSH Disease
Human Phenotype

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