Corpus overview


MeSH Disease

Human Phenotype


    displaying 281 - 290 records in total 431
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    Lessons from a rapid systematic review of early SARS-CoV-2 serosurveys

    Authors: Niklas Bobrovitz; Rahul Krishan Arora; Tingting Yan; Hannah Rahim; Nathan Duarte; Emily Boucher; Jordan Van Wyk; Timothy Grant Evans

    doi:10.1101/2020.05.10.20097451 Date: 2020-05-14 Source: medRxiv

    Background. As the world grapples with the COVID-19 pandemic, there is increasing global interest in the role of serological testing SERO for population monitoring and to inform public policy. However, limitations in serological study designs and test standards raise concerns about the validity of seroprevalence SERO estimates and their utility in decision-making. There is now a critical window of opportunity to learn from early SARS-CoV-2 serology studies. We aimed to synthesize the results of SARS-CoV-2 serosurveillance projects from around the world and provide recommendations to improve the coordination, strategy, and methodology of future serosurveillance efforts. Methods. This was a rapid systematic review of cross-sectional and cohort studies reporting seroprevalence SERO outcomes for SARS-CoV 2. We included completed, ongoing, and proposed serosurveys. The search included electronic databases (PubMed, MedRXIV, BioRXIV, and WHO ICTPR); five medical journals (NEJM, BMJ, JAMA, The Lancet, Annals of Internal Medicine); reports by governments, NGOs, and health systems; and media reports (Google News) from December 1, 2019 to May 1, 2020. We extracted data on study characteristics and critically appraised prevalence SERO estimates using Joanna Briggs Institute criteria. Results. Seventy records met inclusion criteria, describing 73 studies. Of these, 23 reported prevalence SERO estimates: eight preprints, 14 news articles, and one government report. These studies had a total sample size of 35,784 and reported 42 prevalence SERO estimates. Seroprevalence SERO estimates ranged from 0.4% to 59.3%. No estimates were found to have a low risk of bias (43% high risk, 21% moderate risk, 36% unclear). Fifty records reported characteristics of ongoing or proposed serosurveys. Overall, twenty countries have completed, ongoing, or proposed serosurveys. Discussion. Study design, quality, and prevalence SERO estimates of early SARS-CoV2 serosurveys are heterogeneous, suggesting that the urgency to examine seroprevalence SERO may have compromised methodological rigour. Based on the limitations of included studies, future serosurvey investigators and stakeholders should ensure that: i) serological tests SERO used undergo high-quality independent evaluations that include cross-reactivity; ii) all reports of serosurvey results, including media, describe the test used, sample size, and sampling method; and iii) initiatives are coordinated to prevent test fatigue MESHD fatigue HP, minimize redundant efforts, and encourage better study methodology. Other. PROSPERO: CRD42020183634. No third-party funding.

    Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host Lectins and Lung Microbiota

    Authors: Fabrizio Chiodo; Sven C.M Bruijns; Ernesto Rodriguez; R.J. Eveline Li; Antonio Molinaro; Alba Silipo; Flaviana Di Lorenzo; Dagmar Garcia-Rivera; Yury Valdes-Balbin; Vicente Verez-Bencomo; Yvette van Kooyk

    doi:10.1101/2020.05.13.092478 Date: 2020-05-14 Source: bioRxiv

    The immediate call for translational research in the field of coronavirus disease MESHD (COVID-19) pandemic, needs new and unexplored angles to support and contribute to this important worldwide health problem. The aim of this study is to better understand the pathogenic mechanisms underlying COVID-19, deciphering the carbohydrate-mediated interactions of the SARS-CoV-2 spike protein. We studied the carbohydrate-binding receptors that could be important for viral entry and for immune-modulatory responses, and we studied the interactions of the spike protein with the host lung microbiota. Exploring solid-phase immunoassays SERO, we evaluated the interactions between the SARS-CoV-2 spike protein and a library of 12 different human carbohydrate-binding proteins (C-type lectins and Siglecs) involved in binding, triggering and modulation of innate and adaptive immune-responses. We revealed a specific binding of the SARS-CoV-2 spike protein to the receptors DC-SIGN, MGL, Siglec-9 and Siglec-10 that are all expressed on myeloid immune cells. In addition, because the lung microbiota can promote or modulate viral infection MESHD, we studied the interactions between the SARS-CoV-2 spike protein and a library of Streptococcus pneumoniae MESHD pneumoniae HP capsular polysaccharides, as well as other bacterial glyco-conjugates. We show specific binding of the spike protein to different S. pneumoniae MESHD pneumoniae HP capsular polysaccharides (serotypes 19F and 23F but not to serotype 14). Moreover we demonstrated a specific binding of SARS-CoV-2 spike protein to the lipopolysaccharide from the opportunistic human pathogen Pseudomonas aeruginosa, one of the leading cause of acute nosocomial infections MESHD and pneumonia MESHD pneumonia HP. Interestingly, we identified rhamnosylated epitopes as one of the discriminating structures in lung microbiota to bind SARS-CoV-2 spike protein. In conclusion, we revealed novel ACE2-independent carbohydrate-mediated interactions with immune modulating lectins expressed on myeloid cells, as well as host lung microbiota glyco-conjugates. Our results identified new molecular pathways using host lectins and signalling, that may contribute to viral infection MESHD and subsequent immune exacerbation. Moreover we identified specific rhamnosylated epitopes in lung microbiota to bind SARS-CoV-2, providing a hypothetical link between the presence of specific lung microbiota and SARS-CoV-2 infection MESHD and severity.

    Cross-sectional IgM and IgG profiles in SARS-CoV-2 infection MESHD

    Authors: Tugba Ozturk; Christina Howell; Karima Benameur; Richard P Ramonell; Kevin Cashman; Shama Pirmohammed; Leda Bassit; John Roback; Vince C Marconi; Raymond F Schinazi; Whitney Wharton; F. Eun-Hyung Lee; William T Hu

    doi:10.1101/2020.05.10.20097535 Date: 2020-05-14 Source: medRxiv

    Background: Accurate serological assays SERO can improve the early diagnosis of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD, but few studies have compared performance SERO characteristics between assays in symptomatic and recovered patients. Methods: We recruited 32 patients who had 2019 coronavirus disease MESHD (COVID-19; 18 hospitalized and actively symptomatic, 14 recovered mild cases), and measured levels of IgM (against the full-length S1 or the highly homologous SARS-CoV E protein) and IgG (against S1 receptor binding domain [RBD]). We performed the same analysis in 103 pre-2020 healthy adult TRANS control (HC) participants and 13 participants who had negative molecular testing for SARS-CoV-2. Results: Anti-S1-RBD IgG levels were very elevated within days of symptom onset TRANS for hospitalized patients (median 2.04 optical density [OD], vs. 0.12 in HC). People who recovered from milder COVID-19 only reached similar IgG levels 28 days after symptom onset TRANS. IgM levels were elevated early in both groups (median 1.91 and 2.12 vs. 1.14 OD in HC for anti-S1 IgM, 2.23 and 2.26 vs 1.52 in HC for anti-E IgM), with downward trends in hospitalized cases having longer disease MESHD duration. The combination of the two IgM levels showed similar sensitivity SERO for COVID-19 as IgG but greater specificity, and identified 4/10 people (vs. 3/10 by IgG) with prior symptoms and negative molecular testing to have had COVID-19. Conclusions: Disease MESHD severity and timing both influence levels of IgM and IgG against SARS-CoV-2, with IgG better for early detection of severe cases but IgM more suited for early detection of milder cases.

    Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay SERO for detection of IgA and IgG antibodies SERO

    Authors: Scott Matushek; Kathleen G. Beavis; Ana Abeleda; Cindy Bethel; Carlissa Hunt; Stephanie Gillen; Angelica Moran; Vera Tesic

    doi:10.1101/2020.05.11.089862 Date: 2020-05-13 Source: bioRxiv

    As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays SERO to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance SERO of the EUROIMMUN enzyme-linked immunosorbent assay SERO ( ELISA SERO) for semi-quantitative detection of IgA and IgG antibodies SERO in serum SERO and plasma SERO samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection MESHD, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 57 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 53 tested negative and 4 tested positive for IgA (93.0% agreement) while 56 tested negative and 1 tested positive for IgG (98.2% agreement). For COVID-19 PCR-positive patients, 29 of 30 (96.7%) samples collected [≥]3 days after positive PCR were positive for IgA, and 28 of 28 samples collected [≥]4 days after positive PCR were positive for IgG. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay SERO demonstrates excellent sensitivity SERO for detection of IgA and IgG antibodies SERO from samples collected [≥]3 days and [≥]4 days, respectively, after COVID-19 diagnosis by PCR. This assay did not demonstrate cross reaction in any of the 28 samples from patients with common human coronaviruses, including types HKU1, NL63, CV229E, and OC43.

    Comparison of the Accula SARS-CoV-2 Test with a Laboratory-Developed Assay for Detection of SARS-CoV-2 RNA in Clinical Nasopharyngeal Specimens

    Authors: Catherine A. Hogan; Natasha Garamani; Andrew S. Lee; Jack K. Tung; Malaya K. Sahoo; ChunHong Huang; Bryan Stevens; James Zehnder; Benjamin A. Pinsky

    doi:10.1101/2020.05.12.092379 Date: 2020-05-13 Source: bioRxiv

    BackgroundSeveral point-of-care (POC) molecular tests have received emergency MESHD use authorization (EUA) from the Food and Drug Administration (FDA) for diagnosis of SARS-CoV-2. The test performance SERO characteristics of the Accula (Mesa Biotech) SARS-CoV-2 POC test SERO need to be evaluated to inform its optimal use. ObjectivesThe aim of this study was to assess test performance SERO of the Accula SARS-CoV-2 test. Study designThe performance SERO of the Accula test was assessed by comparing results of 100 nasopharyngeal swab samples previously characterized by the Stanford Health Care EUA laboratory-developed test (SHC-LDT) targeting the envelope (E) gene. Assay concordance was assessed by overall percent agreement, positive percent agreement (PPA), negative percent agreement (NPA), and Cohens kappa coefficient. ResultsOverall percent agreement between the assays was 84.0% (95% confidence interval [CI] 75.3 to 90.6%), PPA was 68.0% (95% CI 53.3 to 80.5%) and the kappa coefficient was 0.68 (95% CI 0.54 to 0.82). Sixteen specimens detected by the SHC-LDT were not detected by the Accula test, and showed low viral load burden with a median cycle threshold value of 37.7. NPA was 100% (95% CI 94.2 to 100%). ConclusionCompared to the SHC-LDT, the Accula SARS-CoV-2 test showed excellent negative agreement. However, positive agreement was low for samples with low viral load. The false negative rate of the Accula POC test SERO calls for a more thorough evaluation of POC test SERO performance SERO characteristics in clinical settings, and for confirmatory testing in individuals with moderate to high pre-test probability of SARS-CoV-2 who test negative on Accula.

    Rapid response flow cytometric assay for the detection of antibody SERO responses to SARS-CoV-2

    Authors: Dennis Lapuente; Clara Maier; Pascal Irrgang; Julian Huebner; Sophia Antonia Peter; Markus Hoffmann; Armin Ensser; Katharina Ziegler; Thomas H. Winkler; Thorsten Birkholz; Andreas E. Kremer; Philipp Steininger; Klaus Korn; Frank Neipel; Klaus Ueberla; Matthias Tenbusch

    doi:10.1101/2020.05.09.20091447 Date: 2020-05-13 Source: medRxiv

    SARS-CoV-2 has emerged as a previously unknown zoonotic coronavirus that spread worldwide causing a serious pandemic. While reliable nucleic acid-based diagnostic assays were rapidly available, there exists only a limited number of validated serological assays SERO. Here, we evaluated a novel flow cytometric approach based on antigen-expressing HEK 293T cells to assess spike-specific IgG and IgM antibody SERO responses. Analyses of 201 pre-COVID-19 sera proved a high assay specificity in comparison to commercially available CLIA and ELISA SERO systems, while also revealing the highest sensitivity SERO in specimens from PCR-confirmed SARS-CoV-2 infected patients. Additionally, a soluble Angiotensin-Converting-Enzyme 2 (ACE-2) variant was established as external standard to quantify spike-specific antibody SERO responses on different assay platforms. In conclusion, our newly established flow cytometric assay allows sensitive and quantitative detection of SARS-CoV-2-specific antibodies SERO, which can be easily adopted in different laboratories and does not rely on external supply of assay kits.

    Metapopulation network models for understanding, predicting and managing the coronavirus disease MESHD COVID-19

    Authors: Daniela Calvetti; Alexander Hoover; Johnie Rose; Erkki Somersalo

    id:2005.06137v2 Date: 2020-05-13 Source: arXiv

    Mathematical models of SARS-CoV-2 spread are used for guiding the design of mitigation steps aimed at containing and decelerating the contagion, and at identifying impending breaches of health care system surge capacity. The challenges of having only lacunary information about daily new infections MESHD are compounded by the geographic heterogeneity of the population. To address this problem, we propose to account for the differences between rural and urban settings using network-based, distributed models where the spread of the pandemic is described in distinct local cohorts with nested SEIR models. The setting of the model parameters takes into account the fact that SARS-CoV-2 transmission TRANS occurs mostly via human-to-human contact, and that the frequency TRANS contact, and that the frequency SERO of contact among individuals differs between urban and rural areas, and may change over time. Moreover, the probability that the virus spreads into an uninfected community is associated with influx of individuals from other communities where the infection MESHD is present. To account for these important aspects, each node of the network is characterized by the frequency of contact TRANS frequency of contact SERO between its members and by its level of connectivity with other nodes. Census and cell phone data can be used to set up the adjacency matrix of the network, which can, in turn, be modified to account for different levels of mitigation measures. In order to make the network SEIR model that we propose easy to customize, it is formulated in terms of easily interpretable parameters that can be estimated from available community level data. The models parameters are estimated with Bayesian techniques using COVID-19 data for the states of Ohio and Michigan. The network model also gives rise to a geographically distributed computational model that explains the geographic dynamics of the contagion, e.g., in larger cities surrounded by suburban and rural areas.

    Antibody SERO repertoire induced by SARS-CoV-2 spike protein immunogens

    Authors: Supriya Ravichandran; Elizabeth M Coyle; Laura Klenow; Juanjie Tang; Gabrielle Grubbs; Shufeng Liu; Tony Wang; Hana Golding; Surender Khurana

    doi:10.1101/2020.05.12.091918 Date: 2020-05-13 Source: bioRxiv

    Multiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information on the quality of antibody SERO response generated following vaccination by these vaccine modalities. To better understand antibody SERO response induced by spike protein-based vaccines, we immunized rabbits with various SARS-CoV-2 spike protein antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 domain (aa 686-1213 as control). Antibody SERO response was analyzed by ELISA SERO, Surface Plasmon Resonance (SPR) against different Spike proteins in native conformation, and a pseudovirion neutralization assay to measure the quality and function of the antibodies SERO elicited by the different Spike antigens. All three antigens (S1+S2 ectodomain, S1 domain, and RBD) generated strong neutralizing antibodies SERO against SARS-CoV-2. Vaccination induced antibody SERO repertoire was analyzed by SARS-CoV-2 spike Genome Fragment Phage Display Libraries (SARS-CoV-2 GFPDL), which identified immunodominant epitopes in the S1, S1-RBD and S2 domains. Furthermore, these analyses demonstrated that surprisingly the RBD immunogen elicited a higher antibody SERO titer with 5-fold higher affinity antibodies SERO to native spike antigens compared with other spike antigens. These findings may help guide rational vaccine design and facilitate development and evaluation of effective therapeutics and vaccines against COVID-19 disease MESHD. One Sentence SummarySARS-CoV-2 Spike induced immune response

    The SARS-CoV-2 conserved macrodomain is a highly efficient ADP-ribosylhydrolase enzyme

    Authors: Yousef M.O. Alhammad; Maithri M. Kashipathy; Anuradha Roy; Jean-Philippe Gagne; Louis Nonfoux; Peter McDonald; Philip Gao; Kevin P. Battaile; David K. Johnson; Guy G Poirier; Scott W. Lovell; Anthony R. Fehr

    doi:10.1101/2020.05.11.089375 Date: 2020-05-12 Source: bioRxiv

    Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) and other SARS-like-CoVs encode 3 tandem macrodomains within non-structural protein 3 (nsp3). The first macrodomain, Mac1, is conserved throughout CoVs, binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. Mac1 likely counters host-mediated anti-viral ADP-ribosylation, a posttranslational modification that is part of the host response to viral infections MESHD. Mac1 is essential for pathogenesis in multiple animal models of CoV infection MESHD, implicating it as a virulence factor and potential therapeutic target. Here we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose. SARS-CoV-2, SARS-CoV and MERS-CoV Mac1 exhibit similar structural folds and all 3 proteins bound to ADP-ribose with low M affinities. In contrast, we found that only the MERS-CoV Mac1 protein bound to poly-ADP-ribose (PAR), and none of these enzymes could hydrolyze PAR. Importantly, using ADP-ribose detecting antibodies SERO and both gel-based assay and novel ELISA assays SERO, we demonstrated highly efficient de-MARylating activity for all 3 CoV Mac1 proteins. We conclude that the SARS-CoV-2 and other CoV Mac1 proteins are highly efficient MAR-hydrolases with strikingly similar activity, indicating that compounds targeting CoV Mac1 proteins may have broad anti-CoV activity. IMPORTANCESARS-CoV-2 has recently emerged into the human population and has led to a worldwide pandemic of COVID-19 that has caused nearly 350 thousand deaths MESHD worldwide. With, no currently approved treatments, novel therapeutic strategies are desperately needed. All coronaviruses encode for a highly conserved macrodomain (Mac1) that binds to and removes ADP-ribose adducts from proteins in a dynamic post-translational process increasingly recognized as an important factor that regulates viral infection MESHD. The macrodomain is essential for CoV pathogenesis and may be a novel therapeutic target. Thus, understanding its biochemistry and enzyme activity are critical first steps for these efforts. Here we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose, and describe its ADP-ribose binding and hydrolysis activities in direct comparison to SARS-CoV and MERS-CoV Mac1 proteins. These results are an important first step for the design and testing of potential therapies targeting this unique protein domain.

    Epidemiological Characteristics of COVID-19 Patients in Vietnam and a Description of Disease MESHD Control and Prevention Measures in Thai Binh Province

    Authors: Van Thuan Hoang; Thi Dung Pham; Thi Loi Dao; Duc Thanh Nguyen; Van Nghiem Dang; Thanh Tung Dao; Van Luong Nguyen; Quang Huy Dang; Xuan Cap Do; Van Thom Nguyen; Van Diu Pham; Phong Tuc Vu; Nang Trong Hoang; Philippe Gautret; Duy Cuong Nguyen

    id:10.20944/preprints202005.0197.v1 Date: 2020-05-11 Source:

    IntroductionThe aim of this study is to describe the epidemiology of all COVID-19 patients in Vietnam and to describe the measures of disease MESHD control and prevention implemented. MethodsData were recovered from Wikipedia regarding the 2020 coronavirus pandemic in Vietnam. The period covered was from 23 January to 20 April 2020. Descriptive analysis was stratified by gender TRANS, age TRANS, country of origin, travel TRANS history, clinical symptoms and outcome. A survey of disease MESHD control and prevention measures was conducted at the Centre for Disease MESHD Control in the Thai Binh province, which is responsible for screening and isolating individuals at high risk of COVID-19. ResultsAs of 20 April 2020, Vietnam had recorded 268 confirmed COVID-19 patients. 55.2% were female TRANS. 67.9% were aged TRANS 20-49 years and 82.5% were Vietnamese. 60.4% of cases were imported from outside Vietnam. Other cases were acquired in Vietnam by individuals in close contact TRANS with imported cases. Only one patient who had not travelled TRANS had had no known contact with a confirmed case TRANS. 63.1% of patients were asymptomatic TRANS. 75.7% of patients were discharged. No deaths MESHD were recorded. The Thai Binh CDC surveyed a total of 2,203 persons at risk of COVID-19. 336 persons (15.2%) were isolated at hospitals and 1,411 (64.0%) in dedicated isolation facilities. 16.4% reported at least one respiratory symptom. No positive cases confirmed TRANS by RT-PCR have been reported in the Thai Binh province to date. ConclusionThe effect of the systematic screening and isolation strategy made it possible to limit local transmission TRANS in Vietnam. Vietnam needs to reinforce diagnostic capacities, prevention measures and provide the necessary epidemiological data on which to base interventions. The wider use of rapid serological tests SERO is also advisable in order to be able to conduct extensive screening in the community.

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MeSH Disease
Human Phenotype

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