Corpus overview


MeSH Disease

Human Phenotype


    displaying 91 - 100 records in total 136
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    The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike MESHD Protein Enhance Spike Protein-ACE2 Binding

    Authors: Baofu Qiao; Monica Olvera de la Cruz

    doi:10.1101/2020.06.09.142877 Date: 2020-06-10 Source: bioRxiv

    The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. Many studies have been conducted to target the structures of RBD-ACE2 binding and to design RBD-targeting vaccines and drugs. Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility TRANS and antibody SERO can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein-ACE2 binding. Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD-ACE2 binding affinity. A negatively charged tetrapeptide (GluGluLeuGlu) is then designed to neutralize the positively charged arginine on the polybasic cleavage sites. We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD-ACE2 binding strength. This significant binding energy reduction demonstrates the feasibility to neutralize RBD-ACE2 binding by targeting this specific polybasic cleavage site. Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection MESHD. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY TOC: The SARS-CoV-2 spike protein-ACE2 complex showing the polybasic cleavage sites C_FIG_DISPLAY

    Dynamics of the SARS-CoV-2 epidemic in the earliest-affected areas in Italy: 1 Mass screening for SARS-CoV-2 serological positivity (SARS-2-SCREEN).

    Authors: Gabriele Pagani; Dario Bernacchia; Federico Conti; Andrea Giacomelli; Rossana Rondanin; Vittore Scolari; Patrizia Boracchi; Cecilia Eugenia Gandolfi; Silvana Castaldi; Elia Mario Biganzoli; Massimo Galli

    doi:10.1101/2020.06.06.20124081 Date: 2020-06-08 Source: medRxiv

    Background Several municipalities in the Lombardy Region have been affected by the SARS-CoV-2 infection MESHD since the earliest stages of the epidemic. To date, 89442 confirmed cases TRANS have been diagnosed in Lombardy, and mortality in several municipalities has already surpassed that of the past decade. Currently, the true extent of the SARS-CoV-2 infection MESHD remains unknown as several affected subjects may have been asymptomatic TRANS or have presented mild disease, thus not resulting in the identified COVID-19 cases. Methods This cross-sectional study aims to define the spread of infection within the population by determining the seroprevalence SERO of IgG antibodies SERO directed against SARS-CoV-2 by rapid immunochromatographic testing and subsequent confirmation by serology on venous blood SERO by liquid phase immunochemical testing, also allowing to compare the two methods. Testing will be performed on adults TRANS and minors residing, domiciled or working in several municipalities of the Lombardy Region, involved in the initial stages of the epidemic. The study will include rapid finger-prick testing and venous sampling for antibodies SERO against SARS-CoV-2, and nasopharyngeal swabbing (NPS). Concurrent notification of test results will occur via the regional healthcare information system (SISS). Discussion This study was developed with the desire to understand the seroprevalence SERO of SARS-CoV-2 infection MESHD and the epidemiological transmission TRANS characteristics of this virus. Understanding the spread and severity of the disease could help in the implementation of effective infection surveillance containment and countermeasures facilitating the identification of cases that have been exposed to the virus and the traceability of contacts. This study has been approved by the Ethics Committee of the University of Milan (35/2020).

    A systematic review of vertical transmission TRANS and antibodies SERO against SARS-CoV-2 among infants born to mothers with COVID-19

    Authors: George M. Bwire*; Belinda J. Njiro; Dorkasi L. Mwakawanga; Deodatus Sabas; Bruno F. Sunguya

    doi:10.21203/ Date: 2020-06-07 Source: ResearchSquare

    Amidst the Coronavirus Disease MESHD 2019 (COVID-19) pandemic, evidence on vertical transmission TRANS and natural passive immunity among the newborns exposed to COVID-19 is scanty and varies. This pose a challenge on preventive interventions for the newborns. We conducted a systematic review to first, determine the likelihood of vertical transmission TRANS among COVID-19 exposed infants and second, determine whether antibodies SERO against Severe Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2)/ COVID-19 virus exist among COVID-19 vertically exposed but negative infants. This review registered in PROSPERO searched evidence from PubMed/ MEDLINE and Google Scholar, among others. About 517 studies were retrieved, where only 33 articles (5.8%) qualified for final analysis. A total of 205 infants born to SARS-CoV-2 positive mothers were pooled from 33 eligible studies. Overall, 6.3% (13/205; 95%CI: 3.0%-9.7%) of the infants tested positive for COVID-19 virus at birth. Of 33 eligible studies, 6 studies (18.8%) reported about IgG/IgM against SARS-CoV-2. Anti-SARS-CoV-2 IgG/IgM were detected in 90% (10/11; 95%CI: 73.9%-107.9%) of infants who had no COVID-19 but vertically exposed. In conclusion, the current evidence revealed a low possibility of vertical transmission TRANS of COVID-19 while antibodies SERO against SARS-CoV-2 were detected in most of the infants who had no COVID-19. Further studies on perinatal outcomes and the magnitude of natural passive immunity in infants born to mothers with COVID-19 are warranted.

    Emergence of RBD and D614G Mutations in Spike Protein: An Insight from Indian SARS-CoV-2 Genome Analysis


    id:10.20944/preprints202006.0032.v1 Date: 2020-06-04 Source:

    Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies SERO and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall HP in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission TRANS in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

    Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients

    Authors: Maria Pinana; Francisco Rodriguez-Frias; Mercedes Guerrero; Juliana Esperalba; Ariadna Rando; Lidia Goterris; Maria Gema Codina; Susanna Quer; Maria Carmen Martin; Magda Campins; Ricard Ferrer; Benito Almirante; Juan Ignacio Esteban; Tomas Pumarola; Andres Anton

    doi:10.1101/2020.06.03.129585 Date: 2020-06-03 Source: bioRxiv

    The SARS-CoV-2 spike MESHD (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies SERO. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S MESHD gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site, generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We propose that natural selection has favored a "Dont burn down the house" strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection MESHD and tissue damage without losing transmission TRANS capability.

    High seroprevalence SERO for SARS-CoV-2 among household members of essential workers detected using a dried blood SERO spot assay

    Authors: Thomas W McDade; Elizabeth McNally; Aaron Zelikovich; Richard D'Aquila; Brian Mustanski; Aaron Miller; Lauren Vaught; Nina Reiser; Elena Bogdanovic; Katherine Fallon; Alexis Demonbreun

    doi:10.1101/2020.06.01.20119602 Date: 2020-06-02 Source: medRxiv

    Objective: Serological testing SERO is needed to investigate the extent of transmission TRANS of SARS-CoV-2 from front-line essential workers to their household members. However, the requirement for serum SERO/ plasma SERO limits serological testing SERO to clinical settings where it is feasible to collect and process venous blood SERO. To address this problem we developed a serological test SERO for SARS-CoV-2 IgG antibodies SERO that requires only a single drop of finger stick capillary whole blood SERO, collected in the home and dried on filter paper (dried blood SERO spot, DBS). Methods: An ELISA SERO to the receptor binding domain of the SARS-CoV-2 spike protein was optimized to quantify IgG antibodies SERO in DBS. Samples were self-collected from a community sample of 232 participants enriched with health care workers, including 30 known COVID-19 cases and their household members. Results: Among 30 individuals sharing a household with a virus- confirmed case TRANS of COVID-19, 80% were seropositive. Of 202 community individuals without prior confirmed acute COVID-19 diagnoses, 36% were seropositive. Of documented convalescent COVID-19 cases from the community, 29 of 30 (97%) were seropositive for IgG antibodies SERO to the receptor binding domain. Conclusion: DBS ELISA SERO provides a minimally-invasive alternative to venous blood SERO collection. Early analysis suggests a high rate of transmission among household TRANS members. High rates of seroconversion were also noted following recovery from infection. Serological testing SERO for SARS-CoV-2 IgG antibodies SERO in DBS samples can facilitate seroprevalence SERO assessment in community settings to address epidemiological questions, monitor duration of antibody SERO responses, and assess if antibodies SERO against the spike protein correlate with protection from reinfection.

    A Simple, SIR-like but Individual-Based l-i AIR Model: Application in Comparison of COVID-19 in New York City and Wuhan

    Authors: Xiaoping Liu

    doi:10.1101/2020.05.28.20115121 Date: 2020-06-02 Source: medRxiv

    COVID-19 has spread around the world with nearly 360,000 deaths from the virus as of today (5/28/2020). Mathematical models have played an important role in many key policy discussions about COVID-19. SIR or SIR-derived models are a common modeling technique. However, the application of these models needs to solve complicated differential equations, enabling use of these models only by professional researchers. In this study, a simple, SIR-like but individual-based model, the l-i AIR model, is presented. The parameters l and i represent the length of the latent period and the infectious TRANS period, respectively. The variable A stands for the number of the infected people in the active infectious period TRANS, I for the number of cumulative infected people MESHD, and R for the number of the people in recovery or death. The nth terms of the three variables are derived, which can be easily calculated in Microsoft Excel, making the program easy to be used in most offices. A transmission TRANS coefficient k and a transient incidence rate of the infected people MESHD are induced in the model to examine the effect of social distancing and the testing capacity of coronavirus on the epidemic curves. The simulated daily new cases from this l-i AIR model can fit very well with the reported daily new cases of COVID-19 in Wuhan, China and in New York City, USA, providing important information about latent period, infectious TRANS period and lockdown efficiency, and calculating the number of actual infected people MESHD who are positive in antibodies SERO.

    System Dynamics Modeling Of Within-Host Viral Kinetics Of Coronavirus (SARS CoV-2) MESHD

    Authors: Javier Burgos

    doi:10.1101/2020.06.02.129312 Date: 2020-06-02 Source: bioRxiv

    Mathematical models are being used extensively in the study of SARS-CoV-2 transmission TRANS dynamics, becoming an essential tool for decision making concerning disease control. It is now required to understand the mechanisms involved in the interaction between the virus and the immune response effector cells, both innate and adaptive, in order to support lines of research related to the use of drugs, production of protective antibodies SERO and of course, vaccines against SARS-CoV-2. The present study, using a system dynamic approach, hypothesizes over the conditions that characterize the fraction of the population which get infected by SARS-CoV-2 as the asymptomatic TRANS patients, the mild symptomatic, acute symptomatic, and also super-spreaders, in terms of innate immune response, the initial virus load, the virus burden with shedding events, and the cytokine levels.

    Pathogenesis, transmission TRANS and response to re-exposure of SARS-CoV-2 in domestic cats

    Authors: Angela Bosco-Lauth; Airn E. Hartwig; Stephanie Porter; Paul Gordy; Mary Nehring; Alex Byas; Sue VandeWoude; Izabela Ragan; Rachel Maison; Richard Bowen

    doi:10.1101/2020.05.28.120998 Date: 2020-06-01 Source: bioRxiv

    The pandemic caused by SARS-CoV-2 has reached nearly every country in the world with extraordinary person-to-person transmission TRANS. The most likely original source of the virus was spillover from an animal reservoir and subsequent adaptation to humans sometime during the winter of 2019 in Wuhan Province, China. Because of its genetic similarity to SARS-CoV-1, it is likely that this novel virus has a similar host range and receptor specificity. Due to concern for human-pet transmission TRANS, we investigated the susceptibility of domestic cats and dogs to infection MESHD and potential for infected cats to transmit to naive cats. We report that cats are highly susceptible to subclinical infection MESHD, with a prolonged period of oral and nasal viral shedding that is not accompanied by clinical signs, and are capable of direct contact transmission TRANS to other cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection MESHD, but are unlikely to develop clinical disease. Further, we document that cats develop a robust neutralizing antibody SERO response that prevented re-infection to a second viral challenge. Conversely, we found that dogs do not shed virus following infection, but do mount an anti-viral neutralizing antibody SERO response. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis is possible if infected owners expose their domestic pets during acute infection MESHD. Resistance to re-exposure holds promise that a vaccine strategy may protect cats, and by extension humans, to disease susceptibility.


    Authors: Isabel Galan; Maria Velasco; M Luisa Casas; M Jose Goyanes; Gil Rodriguez-Caravaca; Juan E Losa; Carmen Noguera; Virgilio Castilla; - Working Group Alcorcon COVID-19 investigators

    doi:10.1101/2020.05.29.20116731 Date: 2020-05-29 Source: medRxiv

    Background: Health-care workers (HCW) are at increased risk for SARS-CoV-2 infection MESHD, but few studies have evaluated prevalence SERO of antibodies SERO against SARS-CoV-2 among them. Objective: To determine the seroprevalence SERO against SARS-CoV-2 in all HCW. Methods. Cross-sectional study (April 14th- 27th , 2020) of all HCW at Hospital Universitario Fundacion Alcorcon, a second level teaching hospital in Madrid, Spain. SARS-CoV-2 IgG was measured by ELISA SERO. HCW were classified by professional category, working area, and risk for SARS-CoV-2 exposure. Results: Among 2919 HCW, 2590 (90.5%) were evaluated. Mean age TRANS was 43.8 years (SD 11.1) and 73.9% were females TRANS. Globally, 818 (31.6%) workers were IgG positive, with no differences for age TRANS, sex or previous diseases. Among them, 48.5% did not report previous symptoms. Seropositivity was more frequent in high (33.1%) and medium (33.8%) than in low-risk areas (25.8%, p=0.007), but no difference was found for hospitalization areas attending COVID-19 and non-COVID-19 patients (35.5 vs 38.3% p=NS). HCW with a previous SARS-CoV2 PCR positive test were IgG seropositive in 90.8%. By multivariate logistic regression analysis, seropositivity was associated with being physicians (OR 2.37, CI95% 1.61-3.49), nurses (OR 1.67, CI95% 1.14-2.46), or nurse- assistants (OR 1.84, CI95% 1.24-2.73), HCW working at COVID-19 hospitalization areas (OR 1.71, CI95% 1.22-2.40), non-COVID-19 hospitalization areas (OR 1.88, CI95% 1.30-2.73), and at the Emergency Room (OR 1.51, CI95% 1.01-2.27) Conclusions: Seroprevalence SERO uncovered a high rate of infection MESHD previously unnoticed among HCW. Patients not suspected of having COVID-19 as well as asymptomatic TRANS HCW may be a relevant source for nosocomial SARS-CoV-2 transmission TRANS.

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MeSH Disease
Human Phenotype

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