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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (308)

ProteinN (25)

NSP5 (13)

ORF1ab (8)

ORF8 (5)


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    A rapid assessment of wastewater for genomic surveillance of SARS-CoV-2 variants at sewershed scale in Louisville, KY

    Authors: Joshua Fuqua; Eric Rouchka; Sabine Waigel; Kevin Sokoloski; Donghoon Chung; Wolfgang Zacharias; Mei Zhang; Julia Chariker; Daymond Talley; Ian Santisteban; Arvind Vasrsani; Sarah Moyer; Rochelle H Holm; Ray Yeager; Ted R Smith; Aruni Bhatnagar

    doi:10.1101/2021.03.18.21253604 Date: 2021-03-26 Source: medRxiv

    The successful viral detection of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) RNA in wastewater at various pooled scales (1-4) and discovery in the USA of B.1.1.7 , B.1.351 and P.1 variants (5), has led to an interest in developing reliable population-level wastewater viral genomic surveillance. The diversity of SARS-CoV-2 sequences reported to be circulating in the USA, have been determined by sequencing clinical samples; however, these variants can also be surveilled by sequencing wastewater samples (6-9). As of March 2021, the variants of concern - B.1.1.7, B.1.351, and P.1 have been widely detected in clinical samples from 47 states in the USA. In Kentucky, only five clinical cases have been linked to the presence of these variants (5),which could indicate incomplete surveillance. Broadening the application of genomic surveillance using wastewater in the community could enhance SARS-CoV-2 variant population monitoring. In this communication, we report on the genomic surveillance of SARS-CoV-2 using wastewater samples in Jefferson County, KY. Samples were collected from manholes and treatment facilities, covering populations of 8,000 to 350,000 people (Table 1). RNA isolated from wastewater samples was used to quantify SARS-CoV-2 and analyze the genetic variation through high-throughput sequencing (See Supplementary Methods). Bioinformatics approaches were used to rapidly identify single nucleotide genetic alterations, which were compared with known variants of interest and concern. In February 2021, we analyzed seven wastewater samples for SARS-CoV-2 genomic surveillance (Figure 1). We did not detect genetic variations indicative of any current variant of concern, beyond the widespread D614G spike protein PROTEIN mutation (Supplementary Methods Tables 2-5). In all samples, we identified at least four of ten mutations consistent with the presence of the variant of interest B.1.429, and one sample contained seven of ten mutations (Table 2). The B.1.429 variant was confirmed in patient samples in Kentucky in January 2021 (10), and a single patient in the study area was reported to be positive for B.1.1.7 on February 9, 2021 (11). With our current metrics we flagged sites 833, 891, and Treatment plant #2 for potential presence of variant B.1.429 (3/7 sites). Differences in the scale of sample pooling in the community revealed unanticipated inconsistencies in variant representation. Specifically, variants observed in smaller catchment areas, such as neighborhood manhole locations, were not observed in downstream treatment plants, suggesting catchment size or population could impact the ability to detect diversity. Given the highly variable viral genome sequence coverage recovered from wastewater samples, there is an urgent need to develop a set of consistent thresholds constituting positive/negative presence of a variant. Monitoring SARS-CoV-2 variants in wastewater may warn of an emerging variant of concern and identify variant dominance occurring when a new variant is introduced in a community. Wastewater genetic monitoring may be particularly useful in the context of limited clinical sample sequencing capacity because a broad perspective on the genetic diversity can be obtained from a few samples. To develop comprehensive epidemiological frameworks required to guide policy, population-level wastewater surveillance of viral genetic diversity should be complemented by clinical sample testing.

    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.

    A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

    Authors: Aaron J. Schmitz; Jackson S. Turner; Zhuoming Liu; Ishmael D. Aziati; Rita E. Chen; Astha Joshi; Traci L. Bricker; Tamarand L. Darling; Daniel C. Adelsberg; Wafaa B. Al Soussi; James Brett Case; Tingting Lei; Mahima Thapa; Fatima Amanat; Pei-Yong Shi; Rachel M. Presti; Florian Krammer; Goran Bajic; Sean P.J. Whelan; Michael S. Diamond; Adrianus C.M. Boon

    doi:10.1101/2021.03.24.436864 Date: 2021-03-25 Source: bioRxiv

    The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection MESHD- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein PROTEIN. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation MESHD, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection MESHD or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines MESHD and mitigate resistance by circulating variants of concern.

    Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin MESHD Nanoparticle Vaccine in Nonhuman Primates

    Authors: Michael G. Joyce; Hannah A.D. King; Ines Elakhal Naouar; Aslaa Ahmed; Kristina K. Peachman; Camila M. Cincotta; Caroline Subra; Rita E. Chen; Paul V. Thomas; Wei-Hung Chen; Rajeshwer S. Sankhala; Agnes Hajduczki; Elizabeth J. Martinez; Caroline E. Peterson; William C. Chang; Misook Choe; Clayton Smith; Parker J. Lee; Jarrett A. Headley; Mekdi G. Taddese; Hanne A. Elyard; Anthony Cook; Alexander Anderson; Kathryn McGuckin-Wuertz; Ming Dong; Isabella Swafford; James B. Case; Jeffrey R. Currier; Kerri G. Lal; Sebastian Molnar; Manoj S. Nair; Vincent Dussupt; Sharon P. Daye; Xiankun Zeng; Erica K. Barkei; Hilary M. Staples; Kendra Alfson; Ricardo Carrion; Shelly J. Krebs; Dominic Paquin-Proulx; Nicos Karasavva; Victoria R. Polonis; Linda L. Jagodzinski; Mihret F. Amare; Sandhya Vasan; Paul T. Scott; Yaoxing Huang; David D Ho; Natalia de Val; Michael S. Diamond; Mark G. Lewis; Mangala Rao; Gary R. Matyas; Gregory D. Gromowski; Sheila A. Peel; Nelson L. Michael; Diane L. Bolton; Kayvon Modjarrad

    doi:10.1101/2021.03.24.436523 Date: 2021-03-25 Source: bioRxiv

    The emergence of novel severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 MESHD ( COVID-19 MESHD). We developed and evaluated an adjuvanted SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50 mcg) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response on high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. The potent and broad immunogenicity profile of this vaccine and its resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses.

    SARS-CoV-2 spike PROTEIN protein gene variants with N501T and G142D mutation dominated infections in minks in the US

    Authors: Hugh Y Cai; Allison Cai

    doi:10.1101/2021.03.18.21253734 Date: 2021-03-24 Source: medRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) have infected human and animals world wide. Since the first SARS-CoV-2 sequences identified from samples collected in December 2019, the virus has been evolving. Now, in the GISAID database of SARS-CoV-2 genomes as of March 17, 2021, 95.7% (758,684 of 792,388) of the SARS-CoV-2 genome has the D614G mutation in the spike protein PROTEIN gene; and 22% (178,186 of 792.388) had N501Y mutation which occurred in the more virulent UK variants, South Africa variant and Brazil variant. Large number of minks were infected with the virus which containing the Y453F mutation in Europe, causing zoonosis concerns. To evaluate the genetic characteristics of the US mink-derived SARS-CoV-2 sequences, we analyzed all animal-derived (977), all Canadian (19,529) and US (173,277) SARS-CoV-2 sequences deposited in GISAID from December 2019 to March 12, 2021, and identified 2 dominant novel variants, the N501T-G142D variant and N501T-G142D-F486L variant, in the US mink-derived SARS-CoV-2 sequences. These variants were not found in minks from Canada or other countries. The Y453F mutation was not identified in the mink-derive sequences in the US and Canada. The N501T mutation occurred two months earlier in the human than in the minks in the US. The results of our study highlighted the importance of on going monitoring the mutations of the SARS-CoV-2 virus in animals.

    Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 MESHD recovered individuals

    Authors: Carmen Camara; Daniel Lozano-Ojalvo; Eduardo Lopez-Granados; Estela Paz-Artal; Marjorie Pion; Rafael Correa-Rocha; Alberto Ortiz; Marcos Lopez-Hoyos; Marta Erro Iribarren; Jose Portoles; Pilar Portoles; Mayte Perez-Olmeda; Jesus Oteo-Iglesias; Cecilia Berin; Ernesto Guccione; Antonio Bertoletti; Jordi Ochando

    doi:10.1101/2021.03.22.436441 Date: 2021-03-22 Source: bioRxiv

    The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection MESHD has been questioned. Here we characterized SARS-CoV-2 spike PROTEIN-specific humoral and cellular immunity in naive and previously infected individuals during full BNT162b2 vaccination. Our results demonstrate that the second dose increases both the humoral and cellular immunity in naive individuals. On the contrary, the second BNT162b2 vaccine dose results in a reduction of cellular immunity in COVID-19 MESHD recovered individuals, which suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.

    A bispecific monomeric nanobody induces SARS-COV-2 spike trimer dimers

    Authors: Leo Hanke; Hrishikesh Das; Daniel Sheward; Laura Perez Vidakovics; Egon Urgard; Ainhoa Moliner Morro; Vivien Karl; Alec Pankow; Kim Changil; Natalie Smith; Gabriel Pedersen; Jonathan M Coquet; B Martin Hallberg; Benjamin Murrell; Gerald M McInerney

    doi:10.1101/2021.03.20.436243 Date: 2021-03-21 Source: bioRxiv

    Antibodies binding to the severe acute respiratory syndrome coronavirus 2 MESHD ( SARS-CoV-2) spike PROTEIN have therapeutic promise, but emerging variants show the potential for virus escape. Thus, there is a need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we isolated a nanobody that potently neutralizes SARS-CoV-2, including the B.1.351 variant, and cross-neutralizes SARS-CoV MESHD. We demonstrate the therapeutic potential of the nanobody in a human ACE2 HGNC transgenic mouse model. Using biochemistry and electron cryomicroscopy we show that this nanobody simultaneously interacts with two RBDs from different spike trimers, rapidly inducing the formation of spike trimer-dimers. This naturally elicited bispecific monomeric nanobody establishes a novel strategy for potent immobilization of viral antigens.

    Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study

    Authors: Antonio Leidi; Flora Koegler; Roxane Dumont; Richard Dubos; Maria-Eugenia Zaballa; Giovanni Piumatti; Matteo Coen; Amandine Berner; Pauline Darbellay Farhoumand; Pauline Vetter; Nicolas Vuilleumier; Laurent Kaiser; Delphine Courvoisier; Andrew Azman; Idris Guessous; Silvia Stringhini

    doi:10.1101/2021.03.19.21253889 Date: 2021-03-20 Source: medRxiv

    Importance: Serological assays detecting specific IgG antibodies generated against the Spike protein PROTEIN following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection MESHD are being widely deployed in research studies and clinical practice. However, the duration and the effectiveness of the protection conferred by the immune response against future infection remains to be assessed in a large population. Objective: To estimate the incidence of newly acquired SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD in seropositiveindividuals from a population-based sample as compared to seronegative controls. Design: Retrospective longitudinal propensity-score matched cohort study. Setting: A seroprevalence survey including a population-based representative sample of the population from the canton of Geneva (Switzerland) was conducted between April and June 2020, immediately after the first pandemic wave. Each individual included in the seroprevalence survey was linked to a state centralized registry compiling virologically confirmed SARS-CoV-2 infections MESHD since the beginning of the pandemic. Participants: Participants aged twelve years old and over, who developed anti-spike IgG antibodies were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency MESHD, body mass index, smoking status and education level. Exposure: SARS-CoV-2 seropositivity. Main outcomes and measures: Our primary outcome was virologically confirmed SARS-CoV-2 infections MESHD which occurred from serological status assessment in April-June 2020 to the end of the second pandemic wave (January 2021). Additionally, incidence of infections, rate of testing and proportion of positive tests were analysed. Results: Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (Standard Deviation, SD: 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of which 5 (1.0%) were considered as reinfections. By contrast, infection rate was significantly higher in seronegative individuals (15.5%, 154/996) during a similar mean follow-up of 34.7 (SD 3.2) weeks, corresponding to a 94% (95%CI 86% to 98%, P<0.001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositive subjects. Conclusions and relevance: Seroconversion after SARS-CoV-2 infection MESHD confers protection to successive viral contamination lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.

    Household transmission of SARS-CoV-2 R.1 lineage with spike E484K mutation in Japan

    Authors: Yosuke Hirotsu; Masao Omata

    doi:10.1101/2021.03.16.21253248 Date: 2021-03-20 Source: medRxiv

    We aimed to investigate SARS-CoV-2 emerging lineage harboring variants in receptor binding domain (RBD) of spike protein PROTEIN in Japan. Total nucleic acids were subjected to whole genome sequencing on samples from 133 patients with coronavirus disease MESHD ( COVID-19 MESHD). We obtained the SARS-CoV-2 genome sequence from these patients and examined variants in RBD. As a result, three patients were infected with SARS-CoV-2 harboring E484K mutation in January 2021. These three patients were relatives; one was in the 40s, and two were younger than 10 years old. They had no history of staying abroad and were living in Japan. This strains were classified into GR clade (GISAID), 20B clade (Nextstrain) and R.1 lineage (PANGO). As of March 5, 2021, the R.1 lineage have been identified in 305 samples and dominantly observed in the USA (44%, 135 / 305) and Japan (28%, 84 / 305) from the GISAID database. During the period between October 26, 2020 and February 23, 2021, the frequency of the R.1 lineage was 0.97% (84 / 8,629) of the total confirmed data in Japan and 0.15% (135 / 90,450) in the USA. Although SARS-CoV-2 R.1 lineage was not globally predominant as of March 2021, further analysis is needed to determine whether R.1 variant will disappear or expand in the future.

    Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike PROTEIN antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination

    Authors: Amihai Rottenstreich; Gila Zarbiv; Esther Oiknine-Djian; Roy Zigron; Dana G Wolf; Shay Porat

    doi:10.1101/2021.03.11.21253352 Date: 2021-03-12 Source: medRxiv

    BackgroundSevere acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) during pregnancy and early infancy can result in severe disease. Evaluating the serologic response after maternal vaccination during pregnancy and subsequent transplacental antibody transfer has important implications for maternal care and vaccination strategies. ObjectiveTo assess maternal and neonatal SARS-CoV-2 antibody levels after antenatal mRNA vaccination. Design, Setting, and ParticipantsThis study took place at Hadassah Medical Center in Jerusalem, Israel in February 2021. Maternal and cord blood sera were collected for antibody measurement from mother/newborn dyads following antenatal vaccination. ExposureSARS-CoV-2 BNT162b2 mRNA vaccination. Main outcome and measuresSpike protein (S PROTEIN) and receptor binding domain (RBD) - specific, IgG levels were evaluated in maternal and cord blood sera. ResultsThe study cohort consisted of 20 parturients, with a median maternal age of 32 y ears and a median gestational age of 393/7 weeks at the time of delivery. The median time lapsed from the first and second doses of vaccine administration until delivery was 33 [IQR 30-37] and 11 [IQR 9-15] days, respectively. Of the 20 dyads, all women an d infants were positive for anti S- and anti-RBD-specific IgG. Anti-S and anti-RBD-specific IgG levels in maternal sera were positively correlated to their respective concentrations in cord blood ({rho}s= 0.72; P<0.001 and {rho}s= 0.72; P <0.001, respectively). Anti-S and anti-RBD-specific IgG titers in cord blood were directly correlated with time lapsed since the administration of the first vaccine dose ({rho}s= 0.71; P =0.001 and {rho}s= 0.63; P=0.004, respectively). Conclusion and RelevanceIn this study, SARS-CoV-2 mRNA vaccine administered during pregnancy induced adequate maternal serologic response with subsequent efficient transplacental transfer. Our findings highlight that vaccination of pregnant women may provide maternal and neonatal protection from SARS-CoV-2 infection MESHD.

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MeSH Disease
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SARS-CoV-2 Proteins


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