Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 278
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    Effect of Convalescent Plasma SERO on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience

    Authors: Michael J Joyner; Jonathon W Senefeld; Stephen A Klassen; John R Mills; Patrick W Johnson; Elitza S Theel; Chad C Wiggins; Katelyn A Bruno; Allan M Klompas; Elizabeth R Lesser; Katie L Kunze; Matthew A Sexton; Juan C Diaz Soto; Sarah E Baker; John R.A. Shepherd; Noud van Helmond; Camille M van Buskirk; Jeffrey L Winters; James R Stubbs; Robert F Rea; David O Hodge; Vitaly Herasevich; Emily R Whelan; Andrew J Clayburn; Kathryn F Larson; Juan G Ripoll; Kylie J Andersen; Matthew R Buras; Matthew N.P. Vogt; Joshua J Dennis; Riley J Regimbal; Philippe R Bauer; Janis E Blair; Nigel S Paneth; DeLisa Fairweather; R. Scott Wright; Rickey E Carter; Arturo Casadevall

    doi:10.1101/2020.08.12.20169359 Date: 2020-08-12 Source: medRxiv

    Importance: Passive antibody SERO transfer is a longstanding treatment strategy for infectious diseases MESHD that involve the respiratory system. In this context, human convalescent plasma SERO has been used to treat coronavirus disease MESHD 2019 (COVID-19), but the efficacy remains uncertain. Objective: To explore potential signals of efficacy of COVID-19 convalescent plasma SERO. Design: Open-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma SERO. Setting: Multicenter, including 2,807 acute care facilities in the US and territories. Participants: Adult TRANS participants enrolled and transfused under the purview of the US Convalescent Plasma SERO EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome MESHD. Intervention: Transfusion of at least one unit of human COVID-19 convalescent plasma SERO using standard transfusion guidelines at any time during hospitalization. Convalescent plasma SERO was donated by recently-recovered COVID-19 survivors, and the antibody SERO levels in the units collected were unknown at the time of transfusion. Main Outcomes and Measures: Seven and thirty-day mortality. Results: The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma SERO transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody SERO levels in the transfused plasma SERO. For patients who received high IgG plasma SERO (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma SERO (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma SERO (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody SERO level plasma SERO units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody SERO level plasma SERO units. Conclusions and Relevance: The relationships between reduced mortality and both earlier time to transfusion and higher antibody SERO levels provide signatures of efficacy for convalescent plasma SERO in the treatment of hospitalized COVID-19 patients. This information may be informative for the treatment of COVID-19 and design of randomized clinical trials involving convalescent plasma SERO. Trial Registration: Identifier: NCT04338360

    Elicitation of potent neutralizing antibody SERO responses by designed protein nanoparticle vaccines for SARS-CoV-2

    Authors: Alexandra C Walls; Brooke Fiala; Alexandra Schaefer; Samuel Wrenn; Minh N Pham; Michael Murphy; Longping V Tse; Laila Shehata; Chengbo Chen; Mary Jane Navarro; Marcos C Miranda; Deleah Pettie; Rashmi Ravichandran; John C Kraft; Cassandra Ogohara; Anne Palser; Sara Chalk; E-Chiang Lee; Elizabeth Kepl; Cameron M Chow; Claire Sydeman; Edgar A Hodge; Brieann Brown; Jim T Fuller; Kenneth Dinnon III; Lisa Gralinski; Sarah R Leist; Kendra L Gully; Thomas B Lewis; Miklos Guttman; Helen Y Chu; Kelly K Lee; Deborah H Fuller; Ralph S. Baric; Paul Kellam; Lauren Carter; Marion Pepper; Timothy P Sheahan; David Veesler; Neil P King

    doi:10.1101/2020.08.11.247395 Date: 2020-08-12 Source: bioRxiv

    A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody SERO responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody SERO titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies SERO elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease MESHD. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody SERO responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.

    Efficacy of Targeting SARS-CoV-2 by CAR-NK Cells

    Authors: Minh Tuyet Ma; Saiaditya Badeti; Ke Geng; Dongfang Liu

    doi:10.1101/2020.08.11.247320 Date: 2020-08-12 Source: bioRxiv

    SARS-CoV-2, which causes COVID-19 disease MESHD, is one of greatest global pandemics in history. No effective treatment is currently available for severe COVID-19 disease MESHD. One strategy for implementing cell-based immunity involves the use of chimeric antigen receptor (CAR) technology. Unlike CAR T cells, which need to be developed using primary T cells derived from COVID-19 patients with lymphopenia MESHD lymphopenia HP, clinical success of CAR NK cell immunotherapy is possible through the development of allogeneic, universal, and off-the-shelf CAR-NK cells from a third party, which will significantly broaden the application and reduce costs. Here, we develop a novel approach for the generation of CAR-NK cells for targeting SARS-CoV-2. CAR-NK cells were generated using the scFv domain of CR3022 (henceforth, CR3022-CAR-NK), a broadly neutralizing antibody SERO for SARS-CoV-1 and SARS-CoV-2. CR3022-CAR-NK cells can specifically bind to RBD of SARS-CoV-2 and pseudotyped SARS-CoV-2 S protein, and can be activated by pseudotyped SARS-CoV-2-S viral particles in vitro. Further, CR3022-CAR-NK cells can specifically kill pseudo-SARS-CoV-2 infected target cells. Thus, off-the-shelf CR3022-CAR-NK cells may have the potential to treat patients with severe COVID-19 disease MESHD.

    A diagnostic decision-making protocol combines a new-generation of serological assay SERO and PCR to fully resolve ambiguity in COVID-19 diagnosis

    Authors: Hu Cheng; Hao Chen; Yiting Li; Peiyan Zheng; Dayong Gu; Shiping He; Dongli Ma; Ruifang Wang; Jun Han; Zhongxin Lu; Xinyi Xia; Yi Deng; Lan Yang; Wenwen Xu; Shanhui Wu; Cuiying Liang; Hui Wang; Baoqing Sun; Nanshan Zhong; Hongwei Ma

    doi:10.1101/2020.08.11.20172452 Date: 2020-08-11 Source: medRxiv

    The capacity to accurately diagnosis COVID-19 is essential for effective public health measures to manage the ongoing global pandemic, yet no presently available diagnostic technologies or clinical protocols can achieve full positive predictive value SERO (PPV) and negative predictive value SERO (NPV) performance SERO. Two factors prevent accurate diagnosis: the failure of sampling methods (e.g., 40% false negatives from PCR testing of nasopharyngeal swabs) and sampling-time-dependent failures reflecting individual humoral responses of patients (e.g., serological testing SERO outside of the sero-positive stage). Here, we report development of a diagnostic protocol that achieves full PPV and NPV based on a cohort of 500 confirmed COVID-19 cases, and present several discoveries about the sero-conversion dynamics throughout the disease MESHD course of COVID-19. The fundamental enabling technology for our study and diagnostic protocol-termed SANE, for Symptom (dpo)- Antibody SERO-Nucleic acid-Epidemiological history-is our development of a peptide-protein hybrid microarray (PPHM) for COVID-19. The peptides comprising PPHMCOVID-19 were selected based on clinical sample data, and give our technology the unique capacity to monitor a patient's humoral response throughout the disease MESHD course. Among other assay-development related and clinically relevant findings, our use of PPHMCOVID-19 revealed that 5% of COVID-19 patients are from an "early sero-reversion" subpopulation, thus explaining many of the mis-diagnoses we found in our comparative testing using PCR, CLIA, and PPHMCOVID-19. Accordingly, the full SANE protocol incorporates orthogonal technologies to account for these patient variations, and successfully overcomes both the sampling method and sampling time limitations that have previously prevented doctors from achieving unambiguous, accurate diagnosis of COVID-19

    Comparative analyses of SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibodies SERO from human serum samples SERO

    Authors: Livia Mazzini; Donata Martinuzzi; Inesa Hyseni; Giulia Lapini; Linda Benincasa; Pietro Piu; Claudia Maria Trombetta; Serena Marchi; Ilaria Razzano; Alessandro Manenti; Emanuele Montomoli

    doi:10.1101/2020.08.10.243717 Date: 2020-08-10 Source: bioRxiv

    A newly identified coronavirus, named SARS-CoV-2, emerged in December 2019 in Hubei Province, China, and quickly spread throughout the world; so far, it has caused more than 18 million cases of disease MESHD and 700,000 deaths MESHD. The diagnosis of SARS-CoV-2 infection MESHD is currently based on the detection of viral RNA in nasopharyngeal swabs by means of molecular-based assays, such as real-time RT-PCR. Furthermore, serological assays SERO aimed at detecting different classes of antibodies SERO constitute the best surveillance strategy for gathering information on the humoral immune response to infection MESHD and the spread of the virus through the population, in order to evaluate the immunogenicity of novel future vaccines and medicines for the treatment and prevention of COVID-19 disease MESHD. The aim of this study was to determine SARS-CoV-2-specific antibodies SERO in human serum samples SERO by means of different commercial and in-house ELISA SERO kits, in order to evaluate and compare their results first with one another and then with those yielded by functional assays using wild-type virus. It is important to know the level of SARS-CoV-2-specific IgM, IgG and IgA antibodies SERO in order to predict population immunity and possible cross-reactivity with other coronaviruses and to identify potentially infectious subjects. In addition, in a small sub-group of samples, we performed a subtyping Immunoglobulin G ELISA SERO. Our data showed an excellent statistical correlation between the neutralization titer and the IgG, IgM and IgA ELISA SERO response against the receptor-binding domain of the spike protein, confirming that antibodies SERO against this portion of the virus spike protein are highly neutralizing and that the ELISA SERO Receptor-Binding Domain-based assay can be used as a valid surrogate for the neutralization assay in laboratories which do not have Biosecurity level-3 facilities.

    Neutralizing antibody SERO response in non-hospitalized SARS-CoV-2 patients

    Authors: Natalia Ruetalo; Ramona Businger; Karina Althaus; Simon Fink; Felix Ruoff; Klaus Hamprecht; Bertram Flehmig; Tamam Bakchould; Markus F Templin; Michael Schindler

    doi:10.1101/2020.08.07.20169961 Date: 2020-08-07 Source: medRxiv

    The majority of infections MESHD with SARS-CoV-2 (SCoV2) are asymptomatic TRANS or mild without the necessity of hospitalization. It is of outmost importance to reveal if these patients develop an antibody SERO response against SCoV2 and to define which antibodies SERO confer virus neutralization. We hence conducted a comprehensive serological survey of 49 patients with a mild course of disease MESHD and quantified neutralizing antibody SERO responses against authentic SCoV2 employing human cells as targets. Four patients (8%), even though symptomatic, did not develop antibodies SERO against SCoV2 and two other sera (4%) were only positive in one of the serological assays SERO employed. For the remainder, antibody SERO response against the S-protein correlated with serum SERO neutralization whereas antibodies SERO against the nucleocapsid were poor predictors of virus neutralization. Only six sera (12%) could be classified as highly neutralizing. Furthermore, sera from several individuals with fairly high antibody SERO levels had only poor neutralizing activity. In addition, our data suggest that antibodies SERO against the seasonal coronavirus 229E contribute to SCoV2 neutralization. Altogether, we show that there is a wide breadth of antibody SERO responses against SCoV2 in patients that differentially correlate with virus neutralization. This highlights the difficulty to define reliable surrogate markers for immunity against SCoV2.

    Dynamics of neutralizing antibody SERO titers in the months after SARS-CoV-2 infection MESHD

    Authors: Katharine HD Crawford; Adam S Dingens; Rachel Eguia; Caitlin R Wolf; Naomi Wilcox; Jennifer K Logue; Kiel Shuey; Amanda M Casto; Brooke Fiala; Samuel Wrenn; Deleah Pettie; Neil P King; Helen Y Chu; Jesse D Bloom

    doi:10.1101/2020.08.06.20169367 Date: 2020-08-07 Source: medRxiv

    Most individuals infected with SARS-CoV-2 develop neutralizing antibodies SERO that target the viral spike protein. Here we quantify how levels of these antibodies SERO change in the months following SARS-CoV-2 infection MESHD by examining longitudinal samples collected between {approx}30 and 152 days post- symptom onset TRANS from a prospective cohort of 34 recovered individuals with asymptomatic TRANS, mild, or moderate-severe disease MESHD. Neutralizing antibody SERO titers declined an average of about four-fold from one to four months post- symptom onset TRANS. Importantly, our data are consistent with the expected early immune response to viral infection MESHD, where an initial peak in antibody SERO levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody SERO titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

    Serology assessment of antibody SERO response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test SERO

    Authors: Yang De Marinis; Torgny Sunnerhagen; Pradeep Bompada; Anna Blackberg; Runtao Yang; Joel Svensson; Ola Ekstrom; Karl-Fredrik Eriksson; Ola Hansson; Leif Groop; Isabel Goncalves; Magnus Rasmussen

    doi:10.1101/2020.08.05.20168815 Date: 2020-08-06 Source: medRxiv

    The coronavirus disease MESHD 2019 (COVID-19) pandemic has created a global health- and economic crisis. Lifting confinement restriction and resuming to normality depends greatly on COVID-19 immunity screening. Detection of antibodies SERO to severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection MESHD. In this study, we applied a rapid COVID-19 IgM/IgG antibody test SERO and performed serology assessment of antibody SERO response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n=45), the total antibody SERO detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. We also studied antibody SERO response in relation to time after symptom onset TRANS and disease MESHD severity, and observed an increase in antibody SERO reactivity and distinct distribution patterns of IgM and IgG following disease progression MESHD. The total IgM and IgG detection is 63% in patients with < 2 weeks from disease MESHD onset; 85% in non-hospitalized patients with > 2 weeks disease MESHD duration; and 91% in hospitalized patients with > 2 weeks disease MESHD duration. We also compared different blood SERO sample types and suggest a potentially higher sensitivity SERO by serum SERO/ plasma SERO comparing with whole blood SERO measurement. To study the specificity of the test, we used 69 sera/ plasma SERO samples collected between 2016-2018 prior to the COVID-19 pandemic, and obtained a test specificity of 97%. In summary, our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody SERO detection patterns in association with disease MESHD progress and hospitalization. Our study supports that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.

    The Trend of Neutralizing Antibody SERO Response Against SARS-CoV-2 and the Cytokine/Chemokine Release in Patients with Differing Severities of COVID-19: All Individuals Infected with SARS-CoV-2 Obtained Neutralizing Antibody SERO

    Authors: Lidya Handayani Tjan; Tatsuya Nagano; Koichi Furukawa; Mitsuhiro Nishimura; Jun Arii; Sayo Fujinaka; Sachiyo Iwata; Yoshihiro Nishimura; Yasuko Mori

    doi:10.1101/2020.08.05.20168682 Date: 2020-08-06 Source: medRxiv

    Background: COVID-19 patients show a wide clinical spectrum ranging from mild respiratory symptoms to severe and fatal disease MESHD, and older individuals are known to be affected more severely. Neutralizing antibody SERO for viruses is critical for their elimination, and increased cytokine/chemokine levels are thought to be related to COVID-19 severity. However, the trend of the neutralizing antibody SERO production and cytokine/chemokine levels during the clinical course of COVID-19 patients with differing levels of severity has not been established. Methods: We serially collected 45 blood SERO samples from 12 patients with different levels of COVID-19 severity, and investigated the trend of neutralizing antibody SERO production using authentic SARS-CoV-2 and cytokine/chemokine release in the patients' clinical courses. Results: All 12 individuals infected with SARS-CoV-2 had the neutralizing antibody SERO against it, and the antibodies SERO were induced at approx. 4-10 days after the patients' onsets. The antibodies SERO in the critical and severe cases showed high neutralizing activity in all clinical courses. Most cytokine/chemokine levels were clearly high in the critical patients compared to those with milder symptoms. Conclusion: Neutralizing antibodies SERO against SARS-CoV-2 were induced at a high level in the severe COVID-19 patients, indicating that abundant virus replication occurred. Cytokines/chemokines were expressed more in the critical patients, indicating that high productions of cytokines/chemokines have roles in the disease MESHD severity. These results may indicate that plasma SERO or neutralizing antibody SERO therapy could be a first-line treatment for older patients to eliminate the virus, and corticosteroid therapy could be effective to suppress the cytokine storm after the viral genome's disappearance.

    Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals

    Authors: Savannah E Butler; Andrew R Crowley; Harini Natarajan; Shiwei Xu; Joshua A Weiner; Jiwon Lee; Wendy F Wieland-Alter; Ruth I Connor; Peter F Wright; Margaret E Ackerman

    doi:10.1101/2020.08.05.20168971 Date: 2020-08-06 Source: medRxiv

    Understanding humoral immune responses to SARS-CoV-2 infection MESHD will play a critical role in the development of vaccines and antibody SERO-based interventions. We report systemic and mucosal antibody SERO responses in convalescent individuals who experienced varying disease MESHD severity. Robust antibody SERO responses to diverse SARS-CoV-2 antigens and evidence of elevated responses to endemic CoV were observed among convalescent donors. SARS-CoV-2-specific IgA and IgG responses were often negatively correlated, particularly in mucosal samples, suggesting subject-intrinsic biases in isotype switching. Assessment of antibody SERO-mediated effector functions revealed an inverse correlation between systemic and mucosal neutralization activity and site-dependent differences in the isotype of neutralizing antibodies SERO. Serum SERO neutralization correlated with systemic anti-SARS-CoV-2 IgG and IgM response magnitude, while mucosal neutralization was associated with nasal SARS-CoV-2-specific IgA. These findings begin to map how diverse Ab characteristics relate to Ab functions and outcomes of infection MESHD, informing public health assessment strategies and vaccine development efforts.

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MeSH Disease
Human Phenotype

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