preVIEW: COVID-19

Corpus overview

Overview

MeSH Disease

Coronavirus Infections (99)

COVID-19 (77)

Severe Acute Respiratory Syndrome (28)

Pneumonia (9)

Infections (5)


HGNC Genes

C-reactive protein (4)

angiotensin I converting enzyme 2 (4)

transmembrane serine protease 2 (2)

parathymosin (1)

membrane associated ring-CH-type finger 4 (1)


SARS-CoV-2 proteins

ProteinN (99)

ProteinS (24)

ORF1ab (4)

ORF3a (4)

ProteinS1 (3)


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    Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes

    Authors: Xianwu Pang; Pu Li; Lifeng Zhang; Lusheng Que; Min Dong; Qihui Wang; Yinfeng Wei; Bo Xie; Xing Xie; Lanxiang Li; Chunyue Yin; Liuchun Wei; Qingniao Zhou; Yingfang Li; Lei Yu; Weidong Li; Zengnan Mo; Jing Leng; Yanling Hu

    doi:10.1101/2021.03.31.437666 Date: 2021-03-31 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the cause of the ongoing coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a PROTEIN protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 HGNC structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein PROTEIN with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR HGNC and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

    Multiplex Antibody Analysis of IgM, IgA HGNC and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts

    Authors: Carlota Dobano; Selena Alonso; Marta Vidal; Alfons Jimenez; Rocio Rubio; Rebeca Santano; Diana Barrios; Gemma Pons Tomas; Maria Mele Casas; Maria Hernandez Garcia; Monica Girona-Alarcon; Laura Puyol; Natalia Rodrigo Melero; Carlo Carolis; Aleix Garcia-Miquel; Elisenda Bonet-Carne; Joana Claverol; Marta Cubells; Claudia Fortuny; Victoria Fumado; Anna Codina; Quique Bassat; Carmen Munoz-Almagro; Mariona Fernandez de Sevilla; Eduard Gratacos; Luis Izquierdo; Juan Jose Garcia-Garcia; Ruth Aguilar; Iolanda Jordan; Gemma Moncunill

    doi:10.1101/2021.03.22.21254120 Date: 2021-03-26 Source: medRxiv

    COVID-19 MESHD affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions. We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA HGNC and IgG antibodies against five SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S) and nucleocapsid (N PROTEIN) antigens in the context of a contacts and infectivity longitudinal MESHD study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain. Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection MESHD were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected MESHD individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary. In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection MESHD. Saliva antibody detection could allow determining COVID-19 MESHD prevalence in pediatric populations, alternative to bleeding MESHD or nasal swab, and serological diagnosis following vaccination.

    Detection of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in a fourplex real-time quantitative reverse transcription-PCR assays.

    Authors: Mathieu Durand; Philippe Thibault; Simon Levesque; Ariane Brault; Alex Carignan; Louis Valiquette; Philippe Martin; Simon Labbe

    doi:10.1101/2021.03.23.21254196 Date: 2021-03-26 Source: medRxiv

    The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections MESHD is required to identify and isolate contagious patients to prevent further transmission of the coronavirus disease 2019 MESHD ( COVID-19 MESHD). In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give SARS-CoV-2 a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N PROTEIN) genes. Furthermore, a newly developed primer-probe set targeted human beta-2 microglobulin HGNC ( B2M HGNC) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected less than or equal to 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of 9 logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to detect multiple viral target sequences containing typical mutations of SARS-CoV-2 variants in a single reaction, allowing quicker detection of circulating relevant variants.

    First wastewater surveillance-based city zonation for effective COVID-19 pandemic MESHD preparedness powered by early warning: A study of Ahmedabad, India

    Authors: Manish Kumar; Madhvi Joshi; Anil V Shah; Vaibhav Srivastava; Shyamnarayan Dave

    doi:10.1101/2021.03.18.21253898 Date: 2021-03-20 Source: medRxiv

    Following the proven concept, capabilities, and limitations of detecting the RNA of Severe Acute Respiratory Coronavirus MESHD 2 (SARS-CoV-2) in wastewater, it is pertinent to understand the utility of wastewater surveillance data on various scale. In the present work, we put forward the first wastewater surveillance-based city zonation for effective COVID-19 MESHD pan-demic preparedness. A three-month data of Surveillance of Wastewater for Early Epidemic Prediction (SWEEP) was generated for the world heritage city of Ahmedabad, Gujarat, India. In this expedition, one hundred sixteen wastewater samples were analyzed to detect SARS-CoV-2 RNA, from September 3rd to November 26th, 2020. A total of 111 samples were detected with at least two out of three SARS-CoV-2 genes (N PROTEIN, ORF 1ab, and S). Monthly variation depicted a significant decline in all three genes copies in October compared to September 2020, followed by a sharp increment in November 2020. Correspondingly, the descending order of average genome concentration was: November (~10729 copies/ L) > September (~3047 copies/ L) > October (~454 copies/ L). Monthly variation of SARS-CoV-2 RNA in the wastewater samples may be ascribed to a decline of 19.3% in the total number of active cases in October 2020 and a rise of 1.82% in November 2020. Also, the monthly recovery rate of patients was 16.61, 19.31, and 15.58% in September, October, and Novem-ber 2020, respectively. The percentage change in the genome concentration was observed in the lead of 1-2 weeks with respect to the provisional figures of confirmed cases. SWEEP data-based city zonation was matched with the heat map of the overall COVID-19 MESHD infected population in Ahmedabad city, and month-wise effective RNA concentration variations are shown on the map. The results expound on the potential of WBE surveillance of COVID-19 MESHD as a city zonation tool that can be meaningfully interpreted, predicted, and propagated for community preparedness through advance identification of COVID-19 MESHD hotspots within a given city.

    An In-House ELISA for SARS-CoV-2 RBD MESHD uncovers elevatedimmune response at higher altitudes

    Authors: Rodrigo Tomas Grau; Diego Ploper; Cesar Luis Avila; Esteban Vera Pingitore; Carolina Maldonado; Silvina Chaves; Sergio Benjamin Socias; Agustin Stagnetto; Silvia Navarro; Rossana Chahla; Monica Aguilar; Conrado Llapur; Patricia Aznar; Malena Alcorta; Dardo Costas; Isolina Flores; Gabriela Apfelbaum; Dar Heinze; Raul Mostoslavsky; Gustavo Mostoslavsky; Gabriela Perdigon; Silvia Cazorla; Rosana Chehin

    doi:10.1101/2021.03.10.21252711 Date: 2021-03-12 Source: medRxiv

    The severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) first reported in Wuhan has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) associated represents a challenge for health systems that had to quickly respond developing new diagnostic and therapeutic strategies. In the present work, we developed an In House ELISA with high sensitivity (92.2 %), specificity (100%) and precision (93.9%), with an area under the ROC curve (AUC) of 0.991, rendering the assay as an excellent serological test to correctly discriminate between SARS-COv-2 infected MESHD and non-infected individuals and study population seroprevalence. Among 758 patients evaluated for SARS-CoV-2 diagnosis in the province of Tucuman, Argentina, we found a Pearson correlation coefficient of 0.5048 between antibodies elicited against the RBD and the nucleocapsid (N PROTEIN) antigen. Additionally, 33.6% of individuals diagnosed with COVID-19 MESHD displayed mild levels of RBD-IgG antibodies, while 19% of the patients showed high antibody titers. Interestingly, patients with SARS-COV-2 infection MESHD over 60 years old elicited significantly higher levels of IgG antibodies against RBD compared to younger ones, while no difference was found between women and men. Surprisingly, individuals from a high altitude village displayed statistically significant higher and longer lasting anti-RBD antibodies compared to those from a city at a lower altitude, suggesting that a hypobaric hypoxia MESHD-adapted mechanism may act as a protective factor for COVID-19 MESHD. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-Cov-2 infection MESHD.

    SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

    Authors: Raymond T Suhandynata; Nicholas J Bevins; Jenny T Tran; Deli Huang; Melissa A Hoffman; Kyle Lund; Michael J Kelner; Ronald W McLawhon; Steven L Gonias; David Nemazee; Robert L Fitzgerald

    doi:10.1101/2021.03.10.21253299 Date: 2021-03-12 Source: medRxiv

    Background. The severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated. Methods. The ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay. Results. The Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid PROTEIN) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 MESHD ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 MESHD ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284). Conclusions. The Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected MESHD individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 MESHD NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.

    Evaluation of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 MESHD patients in outbreak on a cruise ship

    Authors: Norihito Kaku; Fumitaka Nishimura; Yui Shigeishi; Rina Tachiki; Hironori Sakai; Daisuke Sasaki; Kenji Ota; Kei Sakamoto; Kosuke Kosai; Hiroo Hasegawa; Koichi Izumikawa; Koya Ariyoshi; Hiroshi Mukae; Jiro Yasuda; Kouichi Morita; Shigeru Konno; Katsunori Yanagihara

    doi:10.1101/2021.03.10.21253064 Date: 2021-03-12 Source: medRxiv

    Background A few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 MESHD ( COVID-19 MESHD) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 MESHD patients. Methods Blood samples were collected from 143 COVID-19 MESHD patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a second SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic MESHD were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins PROTEIN were measured using the enzyme-linked immunosorbent assay to compare false-negative- with positive-result samples. Results Sensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. IgM-, IgG-, and total-antibody positivity rates in the patients with negative results from the second genetic testing were 22.9%, 47.6%, and 72.4%, respectively. All antibody titers, especially those of the IgG antibody against nucleocapsid protein PROTEIN, were significantly lower in blood samples with false-negative results than in those with positive results. Conclusions These findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 MESHD patients than required in the guidelines, and situations in which it is useful are limited.

    Native Hydrophobic Interaction Chromatography Hyphenated to Multi-Angle Light Scattering Detection for In-Process Control of SARS-CoV-2 Nucleocapsid Protein PROTEIN Produced in Escherichia Coli

    Authors: Jelle De Vos; Patricia Pereira Aguilar; Christoph Köppl; Andreas Fischer; Clemens Grünwald-Gruber; Mark Dürkop; Miriam Klausberger; Juergen Mairhofer; Gerald Striedner; Monika Cserjan-Puschmann; Alois Jungbauer; Nico Lingg

    doi:10.26434/chemrxiv.14195318.v1 Date: 2021-03-11 Source: ChemRxiv

    The nucleocapsid protein PROTEIN (NP) of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is critical for several steps of the viral life cycle, and is abundantly expressed during infection, making it an ideal diagnostic target protein. This protein has a strong tendency to dimerization and interaction with nucleic acids. A native hydrophobic interaction chromatography hyphenated to multi-angle light scattering detection (HIC-MALS) method was established for in-process control, in particular, to monitor product fragmentation and multimerization throughout the purification process. High titers of the nucleocapsid protein PROTEIN were expressed in E. coli with a CASPON tag, using a growth-decoupled protein expression system. Purification was accomplished by nuclease treatment of the cell homogenate and a sequence of chromatographic steps. 730 mg purified NP per liter of fermentation could be produced by the optimized process, corresponding to a yield of 77%. The HIC-MALS method was used to demonstrate that the NP product can be produced with a purity of 95%. The molecular mass of the main NP fraction is consistent with dimerized protein as was verified by a complementary native size-exclusion separation (SEC)-MALS analysis. Peptide mapping mass spectrometry and host cell specific enzyme-linked immunosorbent assay confirmed the high product purity, and the presence of a minor endogenous chaperone explained the residual impurities. The HIC-MALS method enables to monitor the purity of the product and simultaneously access its molecular mass.

    Serological reconstruction of COVID-19 MESHD epidemics through analysis of antibody kinetics to SARS-CoV-2 proteins MESHD

    Authors: Stephane Pelleau; Tom Woudenberg; Jason Rosado; Francoise Donnadieu; Laura Garcia; Thomas Obadia; Soazic Gardais; Yasmine Elgharbawy; Aurelie Velay; Maria Gonzalez; Jacques-Yves Nizou; Nizar Khelil; Konstantinos Zannis; Charlotte Cockram; Sarah Merkling; Annalisa Meola; Solen Kerneis; Benjamin Terrier; Jerome de Seze; Delphine Planas; Olivier Schwartz; Francois Dejardin; Stephane Petres; Cassandre von Platen; Laurence Arowas; Louise Perrin de Facci; Darragh Duffy; Cliona Ni Cheallaigh; Niall Conlon; Liam Townsend; Heidi Auerswald; Marija Backovic; Bruno Hoen; Arnaud Fontanet; Ivo Mueller; Samira Fafi-Kremer; Timothee Bruel; Michael T White

    doi:10.1101/2021.03.04.21252532 Date: 2021-03-08 Source: medRxiv

    Infection with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. Waning antibody levels lead to reduced sensitivity of serological diagnostic tests over time. This undermines the utility of serological surveillance as the SARS-CoV-2 pandemic progresses into its second year. Here we develop a multiplex serological test for measuring antibodies of three isotypes (IgG, IgM, IgA) to five SARS-CoV-2 antigens (Spike (S), receptor binding domain (RBD), Nucleocapsid (N PROTEIN), Spike subunit 2, Membrane-Envelope fusion) and the Spike proteins PROTEIN of four seasonal coronaviruses. We measure antibody responses in several cohorts of French and Irish hospitalized patients and healthcare workers followed for up to eleven months after symptom onset. The data are analysed with a mathematical model of antibody kinetics to quantify the duration of antibody responses accounting for inter-individual variation. One year after symptoms, we estimate that 36% (95% range: 11%, 94%) of anti-S IgG remains, 31% (9%, 89%) anti-RBD IgG remains, and 7% (1%, 31%) anti-N IgG remains. Antibodies of the IgM isotype waned more rapidly, with 9% (2%, 32%) anti-RBD IgM remaining after one year. Antibodies of the IgA isotype also waned rapidly, with 10% (3%, 38%) anti-RBD IgA remaining after one year. Quantitative measurements of antibody responses were used to train machine learning algorithms for classification of previous infection and estimation of time since infection. The resulting diagnostic test classified previous infections with 99% specificity and 98% (95% confidence interval: 94%, 99%) sensitivity, with no evidence for declining sensitivity over the time scale considered. The diagnostic test also provided accurate classification of time since infection into intervals of 0 - 3 months, 3 - 6 months, and 6 - 12 months. Finally, we present a computational method for serological reconstruction of past SARS-CoV-2 transmission using the data from this test when applied to samples from a single cross-sectional sero-prevalence survey.

    Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target

    Authors: Takeshi Yamamotoya; Yusuke Nakatsu; Shun Hasei; Yukino Ohata; Jeffrey Encinas; Hisanaka Ito; Takayoshi Okabe; Tomoichiro Asano; Takemasa Sakaguchi

    doi:10.21203/rs.3.rs-284607/v1 Date: 2021-02-28 Source: ResearchSquare

    Novel coronavirus disease 2019 MESHD ( COVID-19 MESHD) has emerged as a global pandemic with far-reaching societal impact. Here we demonstrate that Pin1 is a key cellular molecule necessary for severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) propagation. In this study, siRNA-mediated silencing of Pin1 expression markedly suppressed the proliferation of SARS-CoV-2 in VeroE6/TMPRSS2 cells. In addition, several recently generated Pin1 inhibitors showed strong inhibitory effects on SARS-CoV-2 proliferation, measured by both viral mRNA and protein synthesis, and alleviated the cytopathic effect (CPE) on VeroE6/TMPRSS2 cells. One compound, termed H-77, was found to block SARS-CoV-2 proliferation at an EC50 below 5 µM regardless of whether it was added to the culture medium prior to or after SARS-CoV-2 infection MESHD. The inhibition of viral N protein PROTEIN mRNA synthesis by H-77 implies that the molecular mechanism underlying SARS-CoV-2 inhibition is likely to be associated with viral gene transcription or earlier steps. Another Pin1 inhibitor, all-trans retinoic acid (ATRA)—a commercially available drug used to treat acute promyelocytic leukemia MESHD ( APL MESHD) and which both activates the retinoic acid receptor and inhibits the activity of Pin1—similarly reduced the proliferation of SARS-CoV-2. Taken together, the results indicate that Pin1 inhibitors could serve as potential therapeutic agents for COVID-19 MESHD.

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MeSH Disease
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SARS-CoV-2 Proteins

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