Corpus overview


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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (482)

ProteinS (161)

ComplexRdRp (32)

ProteinE (32)

ORF1ab (25)


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SARS-CoV-2 Proteins
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    Evidence of long-lasting humoral and cellular immunity against SARS-CoV-2 even in elderly COVID-19 MESHD convalescents showing a mild to moderate disease progression

    Authors: Bastian Fischer; Christopher Lindenkamp; Christoph Lichtenberg; Ingvild Edda Birschmann; Cornelius Knabbe; Doris Hendig

    doi:10.1101/2021.02.23.21251891 Date: 2021-02-24 Source: medRxiv

    After the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) MESHD was first identified in China in late 2019, a pandemic evolved that has claimed millions of lives so far. While about 80 % of infections cause mild or moderate COVID-19 MESHD disease, some individuals show a severe progression or even die. Most countries are far from achieving herd-immunity, however, the first approved vaccines offer hope for containment of the virus. Although much is known about the virus, there is a lack of information on the immunity of convalescent individuals. We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 MESHD convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 {+/-} 8.4 years). While anti-SARS-CoV-2 antibodies were still detectable in 95 % of convalescents up to 8 months post infection, an antibody-decay over time was generally observed in most donors. Using a multiplex assay, our data additionally reveal that most convalescents exhibit a broad humoral immunity against different viral epitopes. We demonstrate by flow cytometry that convalescent donors show a significantly elevated number of natural killer cells when compared to healthy controls, while no differences were found concerning other leucocyte subpopulations. We detected a specific long-lasting cellular immune response in convalescents by stimulating immune cells with SARS-CoV-2-specific peptides, covering domains of the viral spike, membrane and nucleocapsid protein PROTEIN, and measuring interferon-{gamma HGNC} ( IFN-{gamma HGNC}) release thereafter. We modified a commercially available ELISA assay for IFN-{gamma HGNC} determination in whole-blood specimens of COVID-19 MESHD convalescents. One advantage of this assay is that it does not require special equipment and can, thus, be performed in any standard laboratory. In conclusion, our study adds knowledge regarding the persistence of immunity of convalescents suffering from mild to moderate COVID-19 MESHD. Moreover, our study provides a set of simple methods to characterize and confirm experienced COVID-19 MESHD.

    Clinical Relevance of Covid-19 MESHD in the Second Half of Pregnancy

    Authors: Marta RUGGIERO; Edgardo Somigliana; Beatrice TASSIS; Letizia LI PIANI; Sara Uceda Renteria; Giussy BARBARA; Giovanna LUNGHI; Enrico FERRAZZI

    doi:10.21203/rs.3.rs-271806/v1 Date: 2021-02-23 Source: ResearchSquare

    Background: Evidence on the outcome of Covid-19 MESHD in pregnancy is generally reassuring but yet not definitive. Methods: To specifically assess the impact of Covid-19 MESHD in the second half of pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias MESHD. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 PROTEIN and S2 of the envelope and those against the nucleoprotein PROTEIN of the nucleocapsid. Women were considered to have had Covid-19 MESHD in pregnancy if at least one of the three assessments was positive. Results: Overall, 28 women had a diagnosis of Covid-19 MESHD in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 MESHD (n=11, 39.3%) compared to unaffected women (n=39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 MESHD in pregnancy included fever MESHD, cough MESHD, dyspnea and anosmia MESHD. Only one woman necessitated intensive care. Pregnancy outcome in women with and without Covid-19 MESHD did not also differ. Conclusions: Covid-19 MESHD is asymptomatic in three out of five women in the second half of pregnancy and is rarely severe. In addition, pregnancy outcome may not be significantly affected.

    Targeting the Coronavirus Nucleocapsid Protein PROTEIN through GSK-3 Inhibition

    Authors: Xiaolei Liu; Anurag Verma; Holly Ramage; Gustavo Garcia; Rebecca L Myers; Anastasia Lucas; Jake J Michaelson; William Coryell; Arvind Kumar; Alexander Charney; Marcelo G. Kazanietz; Daniel J. Rader; Marylyn D. Ritchie; Wade H. Berrettini; Robert Damoiseaux; Vaithilingaraja Arumugaswami; David Schultz; Sara Cherry; Peter S. Klein

    doi:10.1101/2021.02.17.21251933 Date: 2021-02-22 Source: medRxiv

    The coronaviruses responsible for severe acute respiratory syndrome MESHD ( SARS-CoV MESHD), COVID-19 MESHD (SARS-CoV-2), Middle East respiratory syndrome MESHD ( MERS-CoV MESHD), and other coronavirus infections MESHD express a nucleocapsid protein (N PROTEIN) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV MESHD by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication. Here we report that the SARS-CoV-2 N protein PROTEIN contains GSK-3 consensus sequences and that this motif is conserved in diverse coronaviruses, despite limited overall sequence conservation, raising the possibility that SARS-CoV-2 may be sensitive to GSK-3 inhibitors including lithium. We conducted a retrospective analysis of lithium use in patients from three major health systems who were PCR tested for SARS-CoV-2. We found that patients taking lithium have a significantly reduced risk of COVID-19 MESHD (odds ratio = 0.51 [0.34 - 0.76], p = 0.001). We also show that the SARS-CoV-2 N protein PROTEIN is phosphorylated by GSK-3. Knockout of GSK3A HGNC and GSK3B HGNC demonstrates that GSK-3 is essential for N phosphorylation. Alternative GSK-3 inhibitors block N phosphorylation and impair replication in SARS-CoV-2 infected MESHD lung epithelial cells in a cell-type dependent manner. Targeting GSK-3 may therefore provide a new approach to treat COVID-19 MESHD and future coronavirus outbreaks.

    Modeling SARS-CoV-2 infection MESHD and its individual differences with ACE2 HGNC-expressing human iPS cells

    Authors: Emi Sano; Ayaka Sakamoto; Natsumi Mimura; Ai Hirabayashi; Yukiko Muramoto; Takeshi Noda; Takuya Yamamoto; Kazuo Takayama

    doi:10.1101/2021.02.22.432218 Date: 2021-02-22 Source: bioRxiv

    Genetic differences are a primary reason for differences in the susceptibility and severity of coronavirus disease 2019 MESHD ( COVID-19 MESHD). Because induced pluripotent stem MESHD (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD in vitro. Notably, undifferentiated MESHD human iPS cells themselves cannot be infected bySARS-CoV-2. Using adenovirus vectors, here we found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 ( ACE2 HGNC) ( ACE2 HGNC-iPS cells) can be infected with SARS-CoV-2. In infected ACE2 HGNC-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein PROTEIN, the budding of viral particles, the production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We also evaluated COVID-19 MESHD therapeutic drugs in ACE2 HGNC-iPS cells and confirmed the strong antiviral effects of Remdesivir, EIDD-2801, and interferon-beta HGNC. In addition, we performed SARS-CoV-2 infection MESHD experiments on ACE2 HGNC-iPS/ES cells from 8 individuals. Male iPS/ES cells were more capable of producing the virus as compared with female iPS/ES cells. These findings suggest that ACE2 HGNC-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection MESHD in vitro, but they are also a useful resource to clarify the causes of individual differences in COVID-19 MESHD due to genetic differences.

    Diagnostic Performance of Pooled RT-PCR Testing for SARS-CoV-2 Detection

    Authors: Diadem Ricarte; Aubrey Gador; Leomill Mendiola; Ian Christian Gonzales

    doi:10.1101/2021.02.17.21251961 Date: 2021-02-19 Source: medRxiv

    BackgroundWith the high number of COVID-19 MESHD cases, a need to optimize testing strategy must be regarded to obtain timely diagnosis for early containment measures. With this, several studies have employed pooled RT-PCR testing for SARS-CoV-2 as this could potentially conserve laboratory resources while has the capacity to test several individuals. However, this was recommended to firstly validate the method as different laboratory reagents and equipment vary with its diagnostic performance. ObjectiveThe aim of this study was to determine the diagnostic performance of pooled SARS-CoV-2 nasopharyngeal/oropharyngeal swabbed samples using RT-PCR technique. MethodsA records review of two-staged pooled RT-PCR testing data from August 10, 26, 30 and September 5, 2020 was utilized from Northern Mindanao Medical Center COVID-19 MESHD Satellite Laboratory (formerly CHDNM TB Regional Center). For the first stage, using known samples, a total of 30 pools were made for each of the pooling size, 5- and 10-pooled, on both pooling phase, pre- and post-RNA extraction. One positive individual was used to represent each of the Cycle threshold values given (<24, 25-28, 29-32, 33-36, and 37-40) while the rest of the samples were negative. For the second stage, 54 pools of five from 270 random unknown samples were used to validate the results. Target gene performance of N gene PROTEIN and RdRp PROTEIN was also determined. Key ResultsResults show that 5-pooled sample has higher sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of 100% (95% confidence interval (CI) 88.97-100), 66.95% (95% CI, 60.75-72.6), 28.18% (95% CI, 20.62-37.22), and 100% (95% CI, 97.66-100) compared to 10-pooled sample that has 87.1% (95% CI, 71.15-94.87), 56.9% (50.57-63.02), 20.77% (95% CI, 14.68-28.53) and 97.14% (95% CI, 92.88-98.88). Further, these Ct values were only from the N gene PROTEIN, emphasizing its higher diagnostic performance as well to detect SARS-CoV-2 compared to RdRp PROTEIN as only a few samples were detected, thus, no analysis was made. ConclusionThis study found out that 5-pooled sample has better diagnostic performance compared to 10-pooled samples. Specifically, all positive individual samples were detected in 5-pooled samples in pre-RNA extraction phase which these results are evident and consistent on both known and unknown samples. N gene PROTEIN was found out to detect more SARS-CoV-2 samples compared to RdRp PROTEIN.

    COVID-BioB Cohort Study: the neutralizing antibody response to SARS-CoV-2 in symptomatic COVID-19 MESHD is persistent and critical for virus control and survival.

    Authors: Stefania Dispinseri; Massimiliano Secchi; Maria Franca Pirillo; Monica Tolazzi; Martina Borghi; Cristina Brigatti; Maria Laura De Angelis; Marco Baratella; Elena Bazzigaluppi; Giulietta Venturi; Francesca Sironi; Andrea Canitano; Ilaria Marzinotto; Cristina Tresoldi; Fabio Ciceri; Lorenzo Piemonti; Donatella Negri; Andrea Cara; Vito Lampasona; Gabriella Scarlatti

    doi:10.1101/2021.02.17.21251929 Date: 2021-02-19 Source: medRxiv

    Understanding how antibody to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches to prevent fatal COVID-19 MESHD illness and vaccines. Here, we profile the antibody response of 162 well-characterized COVID-19 MESHD symptomatic patients followed longitudinally for up to eight months from symptom onset. Using two newly developed assays we detect SARS-CoV-2 neutralization and antibodies binding to Spike antigens and nucleoprotein PROTEIN as well as to Spike S2 antigen of seasonal beta-coronaviruses, and to hemagglutinin of the H1N1 flu virus. Presence of neutralizing antibodies withing the first weeks from symptom onset correlates with time to a negative swab result (p=0.002) while lack of neutralization with an increased risk of a fatal disease outcome (HR 2.918, 95%CI 1.321-6.449; p=0.008). Neutralizing antibody titers progressively drop after 5-8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities. IgG to Spike antigens are the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporary boosted and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Thus, a compromised immune response to the Spike rather than an enhanced one is a major trait of patients with critical conditions. Patients should be promptly identified and immediately start therapeutic interventions aimed at restoring their immunity.

    SARS-CoV-2 nucleocapsid protein PROTEIN dually regulates innate immune responses

    Authors: Yinghua Zhao; Liyan Sui; Ping Wu; Wenfang Wang; Guangyun Tan; Zedong Wang; Yang Yu; Zhijun Hou; Guoqing Wang; Quan Liu

    doi:10.1101/2021.02.17.431755 Date: 2021-02-18 Source: bioRxiv

    The recently emerged severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causative agent of the ongoing global pandemic of COVID-19 MESHD, may trigger immunosuppression in the early stage and a cytokine storm in the late stage of infection, however, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein PROTEIN dually regulated innate immune responses, i.e., the low-dose N protein PROTEIN suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein PROTEIN promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein PROTEIN interacted with the tripartite motif protein 25 ( TRIM25 HGNC), thereby dually regulating the phosphorylation and nuclear translocation of IRF3 HGNC, STAT1 HGNC and STAT2 HGNC. Additionally, low-dose N protein PROTEIN combined with TRIM25 HGNC could suppress retinoic acid-inducible gene I ( RIG-I HGNC) ubiquitination and activation. Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein PROTEIN, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19 MESHD.

    The Prognostic Value of Myocardial Injury MESHD in COVID-19 MESHD Patients and Associated Characteristics

    Authors: jian he; Bicheng Zhang; Quan Zhou; Wenjing Yang; Jing Xu; Tingting Liu; Haijun Zhang; Zhiyong Wu; Dong Li; Qing Zhou; Jie Yan; Cuizhen Zhang; Robert G. Weiss; Guanshu Liu; Zhongzhao Teng; Arlene Sirajuddin; Haiyan Qian; Shihua Zhao; Andrew E. Arai; Minjie Lu; Xiaoyang Zhou

    doi:10.21203/rs.3.rs-251810/v1 Date: 2021-02-17 Source: ResearchSquare

    Background: Since December 2019, Coronavirus disease 2019 MESHD ( COVID-19 MESHD) has emerged as an international pandemic. COVID-19 MESHD patients with myocardial injury MESHD might need special attention. However, understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury MESHD to COVID-19 MESHD patients. Methods: This retrospective, single-center study finally included 304 hospitalized COVID-19 MESHD cases confirmed by real-time RT-PCR from January 11 to March 25, 2020. Myocardial injury MESHD was determined by serum high-sensitivity troponin I (Hs-TnI). The primary endpoint was COVID-19 MESHD associated mortality. Results: Of 304 COVID-19 MESHD patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury MESHD, 27 patients without myocardial injury MESHD on admission). COVID-19 MESHD patients with myocardial injury MESHD had more comorbidities ( hypertension MESHD, chronic obstructive pulmonary disease MESHD, cardiovascular disease MESHD, and cerebrovascular disease MESHD); lower lymphocyte counts, higher C-reactive protein HGNC ( CRP HGNC, median, 84.9 vs 28.5 mg/L, p<0.001), procalcitonin levels (median, 0.29 vs 0.06 ng/ml, p<0.001), inflammatory and immune response markers; more frequent need for noninvasive ventilation, invasive mechanical ventilation; and was associated with higher mortality incidence (hazard ratio, HR=7.02, 95% confidence interval, CI, 4.45-11.08, p<0.001) than those without myocardial injury MESHD. Myocardial injury MESHD (HR=4.55, 95% CI, 2.49-8.31, p<0.001), senior age, CRP HGNC levels, and novel coronavirus pneumonia MESHD ( NCP PROTEIN) types on admission were independent predictors to mortality in COVID-19 MESHD patients. Conclusions: COVID patients with myocardial injury MESHD on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury MESHD and higher HsTNI are both strongest independent predictors to COVID related mortality after adjusting confounding factors. In addition, senior age, CRP HGNC levels and NCP PROTEIN types are also associated with mortality. Trial registration: Not applicable.

    SARS-CoV-2 antibody immunoassays in serial samples reveal earlier seroconversion in acutely ill COVID-19 MESHD patients developing ARDS MESHD

    Authors: Marie-Luise Buchholtz; Florian M. Arend; Peter Eichhorn; Michael Weigand; Alisa Kleinhempel; Kurt Häusler; Mathias Bruegel; Lesca M. Holdt; Daniel Teupser

    doi:10.1101/2021.02.15.21250916 Date: 2021-02-16 Source: medRxiv

    Objectives: During the COVID-19 pandemic MESHD, SARS-CoV-2 antibody testing has been suggested for (1) screening populations for disease prevalence, (2) diagnostics, and (3) guiding therapeutic applications. Here, we conducted a detailed clinical evaluation of four Anti-SARS-CoV-2 immunoassays in samples from acutely ill COVID19 MESHD patients and in two negative cohorts. Methods: 443 serum specimens from serial sampling of 29 COVID-19 MESHD patients were used to determine clinical sensitivities. Patients were stratified for the presence of acute respiratory distress syndrome MESHD ( ARDS MESHD). Individual serum specimens from a pre- COVID-19 MESHD cohort of 238 healthy subjects and from a PCR-negative clinical cohort of 257 patients were used to determine clinical specificities. All samples were measured side-by-side with the Anti-SARS-CoV-2-ELISA (IgG), Anti-SARS-CoV-2-ELISA (IgA) and Anti-SARS-CoV-2- NCP PROTEIN-ELISA (IgG) (Euroimmun AG, Lubeck, Germany) and the Elecsys Anti-SARS-CoV-2 ECLIA (Roche Diagnostics International, Rotkreuz, Switzerland). Results: Median seroconversion occurred earlier in ARDS MESHD patients (8-9 days) than in non- ARDS MESHD patients (11-17 days), except for EUR N-IgG. Rates of positivity and mean signal ratios in the ARDS MESHD group were significantly higher than in the non- ARDS MESHD group. Sensitivities between the four tested immunoassays were equivalent. In the set of negative samples, the specificity of the Anti-SARS-CoV-2-ELISA (IgA) was lower (93.9 %) compared to all other assays ([≥]98.8 %) and the specificity of Anti-SARS-CoV- 2- NCP PROTEIN-ELISA (IgG) was lower (98.8 %) than that of Elecsys Anti-SARS-CoV-2 (100 %). Conclusions: Serial sampling in COVID-19 MESHD patients revealed earlier seroconversion and higher signal ratios of SARS-CoV-2 antibodies as a potential risk marker for the development of ARDS MESHD, suggesting a utility for antibody testing in acutely diseased patients.

    Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases MESHD

    Authors: Claire Deakin; Georgina Cornish; Kevin Ng; Nikhil Faulkner; William Bolland; Veera Panova; Joshua Hope; Annachiara Rosa; Ruth Harvey; Saira Hussain; Chris Earl; Bethany Jebson; Merry Wilkinson; Lucy Marshall; Lizzy Rosser; Ania Radziszewska; Hannah Peckham; Judith Heaney; Hannah Rickman; Stavroula Paraskevopoulou; Catherine Houlihan; Moria Spyer; Steve Gamblin; John Mccauley; Eleni Nastouli; Peter Cherepanov; Coziana Ciurtin; Lucy Wedderburn; George Kassiotis

    doi:10.1101/2021.02.15.431291 Date: 2021-02-16 Source: bioRxiv

    Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction MESHD or suppression unknown. Here, we examined the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases MESHD, juvenile idiopathic arthritis MESHD ( JIA MESHD), juvenile dermatomyositis MESHD ( JDM MESHD) and juvenile systemic lupus erythematosus MESHD ( JSLE MESHD), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects MESHD this age group. Despite immune dysfunction and immunosuppressive treatment, JIA MESHD, JDM MESHD and JSLE MESHD patients mounted comparable or stronger responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike MESHD, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN. In contrast, responses to HCoV-OC43 and SARS-CoV-2 MESHD nucleoproteins PROTEIN exhibited delayed age-dependent class-switching and were not elevated in JIA MESHD, JDM MESHD and JSLE MESHD patients, arguing against increased exposure. Consequently, autoimmune rheumatic diseases MESHD and their treatment were associated with a favourable ratio of spike to nucleoprotein PROTEIN antibodies.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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