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Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection MESHD, and cancer therapy

    Authors: Sierra M. Barone; Alberta G.A. Paul; Lyndsey M. Muehling; Joanne A. Lannigan; William W. Kwok; Ronald B. Turner; Judith A. Woodfolk; Jonathan M. Irish

    doi:10.1101/2020.07.31.190454 Date: 2020-08-01 Source: bioRxiv

    For an emerging disease MESHD like COVID-19, systems immunology tools may quickly identify and quantitatively characterize cells associated with disease progression MESHD or clinical response. With repeated sampling, immune monitoring creates a real-time portrait of the cells reacting to a novel virus before disease MESHD specific knowledge and tools are established. However, single cell analysis tools can struggle to reveal rare cells that are under 0.1% of the population. Here, the machine learning workflow Tracking Responders Expanding (T-REX) was created to identify changes in both very rare and common cells in diverse human immune monitoring settings. T-REX identified cells that were highly similar in phenotype and localized to hotspots of significant change during rhinovirus and SARS-CoV-2 infections MESHD. MHC tetramers were not used during unsupervised analysis and instead "left out" to serve as a test of whether T-REX identifies biologically significant cells. In the rhinovirus challenge study, T-REX identified virus-specific CD4 + T cells based on these cells being a distinct phenotype that expanded by [≥]95% following infection MESHD. T-REX successfully identified hotspots with virus-specific T cells using pairs of samples comparing Day 7 of infection MESHD to samples taken either after clearing the infection MESHD (Day 28) or samples taken prior to infection MESHD (Day 0). Mapping pairwise comparisons in samples according to both the direction and degree of change provided a framework to compare systems level immune changes during infectious disease MESHD or therapy response. This revealed that the magnitude and direction of systemic immune change in some COVID-19 patients was comparable to that of blast crisis MESHD acute myeloid leukemia MESHD acute myeloid leukemia HP patients undergoing induction chemotherapy and characterized the identity of the immune cells that changed the most. Other COVID-19 patients instead matched an immune trajectory like that of individuals with rhinovirus infection MESHD or melanoma MESHD melanoma HP patients receiving checkpoint inhibitor therapy. T-REX analysis of paired blood SERO samples provides an approach to rapidly identify and characterize mechanistically significant cells and to place emerging diseases MESHD into a systems immunology context.

    Persistence of anti- SARS-CoV-2 antibodies SERO in non-hospitalized COVID-19 convalescent health care workers

    Authors: Margherita Bruni; Valentina Cecatiello; Angelica Diaz-Basabe; Georgia Lattanzi; Erika Mileti; Silvia Monzani; Laura Pirovano; Francesca Rizzelli; Clara Visintin; Giuseppina Bonizzi; Marco Giani; Marialuisa Lavitrano; Silvia Faravelli; Federico Forneris; Flavio Caprioli; Pier Giuseppe Pelicci; Gioacchino Natoli; Sebastiano Pasqualato; Marina Mapelli; Federica Facciotti

    doi:10.1101/2020.07.30.20164368 Date: 2020-08-01 Source: medRxiv

    Background. Coronavirus disease MESHD-19 (COVID-19) is a respiratory illness caused by the Severe Acute Respiratory Syndrome MESHD CoronaVirus 2 (SARS-CoV-2), a novel beta-coronavirus. Although antibody SERO response to SARS-CoV-2 can be detected early during the infection MESHD, several outstanding questions remain to be addressed regarding magnitude and persistence of antibody SERO titer against different viral proteins and their correlation with the strength of the immune response, as measured by serum SERO levels of pro-inflammatory mediators. Methods. An ELISA assay SERO has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length nucleocapsid protein (N protein). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies SERO as well as soluble pro-inflammatory mediators in the sera. Results. Specificity and sensitivity SERO of the ELISA assays SERO were high for anti-RBD IgG and IgA (92-97%) and slightly lower for IgM and the Spike and N proteins (70-85%). The ELISA SERO allowed quantification of IgM, IgG and IgA antibody SERO responses against all the viral antigens tested and showed a correlation between magnitude of the antibody SERO response and disease MESHD severity. Non-hospitalized subjects showed lower antibody SERO titers and blood SERO pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested SERO. Noteworthy, in non-severe COVID-19 infections MESHD, antibody SERO titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Conclusions. Rapid decline in antibody SERO titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection MESHD, suggesting that antibody SERO-mediated protection against re- infection MESHD with SARS-CoV-2 is of short duration. These results suggest caution in use serological testing SERO to estimate the prevalence SERO of SARS-CoV-2 infection MESHD in the general population.

    Disease MESHD severity dictates SARS-CoV-2-specific neutralizing antibody SERO responses in COVID-19

    Authors: Xiangyu Chen; Zhiwei Pan; Shuai Yue; Fei Yu; Junsong Zhang; Yang Yang; Ren Li; Bingfeng Liu; Xiaofan Yang; Leiqiong Gao; Zhirong Li; Yao Lin; Qizhao Huang; Lifan Xu; Jianfang Tang; Li Hu; Jing Zhao; Pinghuang Liu; Guozhong Zhang; Yaokai Chen; Kai Deng; Lilin Ye

    doi:10.1101/2020.07.29.20164285 Date: 2020-07-30 Source: medRxiv

    COVID-19 patients exhibit differential disease MESHD severity after SARS-CoV-2 infection MESHD. It is currently unknown as to the correlation between the magnitude of neutralizing antibody SERO (NAb) responses and the disease MESHD severity in COVID-19 patients. In a cohort of 59 recovered patients with disease MESHD severity including severe, moderate, mild and asymptomatic TRANS, we observed the positive correlation between serum SERO neutralizing capacity and disease MESHD severity, in particular, the highest NAb capacity in sera from the patients with severe disease MESHD, while a lack of ability of asymptomatic TRANS patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease MESHD severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic TRANS or mild illness.

    Use of a humanized anti-CD6 monoclonal antibody SERO (itolizumab) in elderly TRANS patients with moderate COVID-19

    Authors: Mayra Ramos-Suzarte; Yayquier Diaz; Yordanis Martin; Nestor Antonio Calderon; William Santiago; Orlando Vinet; Yulieski La O; Jorge Perez; Augusto Oyarzabal; Yoan Perez; Geidy Lorenzo; Meylan Cepeda; Danay Saavedra; Zayma Mazorra; Daymys Estevez; Patricia Lorenzo-Luaces; Carmen Valenzuela; Armando Caballero; Kalet leon; Tania Crombet; Carlos Jorge Hidalgo

    doi:10.1101/2020.07.24.20153833 Date: 2020-07-30 Source: medRxiv

    Abstract Introduction: The Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease MESHD (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11. Elderly TRANS with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection MESHD. During the outbreak, a local transmission TRANS event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly TRANS residents were positive for SARS-CoV-2. Methods: Based on the increased susceptibility to viral-induced cytokine release syndrome MESHD inducing respiratory and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody SERO. Results: All the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease MESHD was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age TRANS, comorbidities and severity of the disease MESHD. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented. Discussion/Conclusion: Itolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 serum SERO levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death MESHD. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 disease MESHD worsening and mortality. The humanized antibody SERO itolizumab emerges as a therapeutic alternative for patients with COVID-19 and suggests its possible use in patients with cytokine release syndrome MESHD from other pathologies.

    Cell-Free DNA in Blood SERO Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity

    Authors: Alexandre Pellan Cheng; Matthew Pellan Cheng; Wei Gu; Joan Sesing Lenz; Elaine Hsu; Erwin Schurr; Guillaume Bourque; Mathieu Bourgey; Jerome Ritz; Francisco M Marty; Charles Y Chiu; Donald Cuong Vinh; Iwijn De Vlaminck

    doi:10.1101/2020.07.27.20163188 Date: 2020-07-29 Source: medRxiv

    COVID-19 primarily affects the lungs, but evidence of systemic disease MESHD with multi-organ involvement is emerging. Here, we developed a blood SERO test to broadly quantify cell, tissue, and organ specific injury due to COVID-19, using genome-wide methylation profiling of circulating cell-free DNA in plasma SERO. We assessed the utility of this test to identify subjects with severe disease MESHD in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma SERO samples from 33 COVID-19 patients and compared to samples from patients with other viral infections MESHD and healthy controls. We found evidence of injury to the lung MESHD and liver and involvement of red blood SERO cell progenitors associated with severe COVID-19. The concentration of cfDNA correlated with the WHO ordinal scale for disease progression MESHD and was significantly increased in patients requiring intubation. This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.

    Infection MESHD of human lymphomononuclear cells by SARS-CoV-2

    Authors: Marjorie C Pontelli; Italo A Castro; Ronaldo B Martins; Flavio P Veras; Leonardo LaSerra; Daniele C Nascimento; Ricardo S Cardoso; Roberta Rosales; Diego B Caetite; Mikhael HF Lima; Thais M Lima; Juliano P Souza; Juliana T Kawahisa; Marcela C Giannini; Leticia P Bonjorno; Maria IF Lopes; Sabrina S Batah; Li Siyuan; Rodrigo L Assad; Sergio CL Almeida; Fabiola R Oliveira; Maira N Benatti; Lorena LF Pontes; Rodrigo C Santana; Fernando C Villar; Maria A Martins; Thiago M Cunha; Rodrigo T Calado; Jose C Alves-Filho; Dario S Zamboni; Alexandre Fabro; Paulo Louzada-Junior; Paulo Louzada-Junior; Rene DR Oliveira; Fernando Q Cunha; Eurico Arruda

    doi:10.1101/2020.07.28.225912 Date: 2020-07-29 Source: bioRxiv

    Although SARS-CoV-2 severe infection HP infection MESHD is associated with a hyperinflammatory state, lymphopenia MESHD lymphopenia HP is an immunological hallmark, and correlates with poor prognosis in COVID-19. However, it remains unknown if circulating human lymphocytes and monocytes are susceptible to SARS-CoV-2 infection MESHD. In this study, SARS-CoV-2 infection MESHD of human peripheral blood SERO mononuclear cells (PBMCs) was investigated both in vitro and in vivo. We found that in vitro infection MESHD of whole PBMCs from healthy donors was productive of virus progeny. Results revealed that monocytes, as well as B and T lymphocytes, are susceptible to SARS-CoV-2 active infection MESHD and viral replication was indicated by detection of double-stranded RNA. Moreover, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from COVID-19 patients, and less frequently in CD4+T lymphocytes. The rates of SARS-CoV-2-infected monocytes in PBMCs from COVID-19 patients increased over time from symptom onset TRANS. Additionally, SARS-CoV-2-positive monocytes and B and CD4+T lymphocytes were detected by immunohistochemistry in post mortem lung tissue. SARS-CoV-2 infection MESHD of blood SERO circulating leukocytes in COVID-19 patients may have important implications for disease MESHD pathogenesis, immune dysfunction, and virus spread within the host.

    PLEXIT - Therapeutic plasma SERO exchange (TPE) for Covid-19 cytokine release storm (CRS), a retrospective propensity matched control study

    Authors: sultan mehmood kamran; Zill -e Humayun Mirza; Arshad Naseem; Jahanzeb Liaqat; Imran Fazal; Wasim Alamgir; Farrukh Saeed; Rizwan Azam; Maryam Hussain; Muhammad Ali Yousaf; Nadeem Ashraf; Shazia Nisar; Muhammad Zafar Ali; Salman Saleem; Kaswar Sajjad; Asad Zaman; Malik Nadeem Azam; Mehmood Hussain; raheel iftikhar

    doi:10.1101/2020.07.23.20160796 Date: 2020-07-29 Source: medRxiv

    Importance: Cytokine release storm (CRS) plays pivotal role in pathophysiology and progression of COVID-19. Objective: To evaluate the outcomes of COVID-19 patients having CRS treated with Therapeutic Plasma SERO Exchange (TPE) as compared to controls not receiving TPE. Design: Retrospective propensity score (PS) matched analysis, 1st April to 30th June 2020. Setting: Tertiary care hospital, single centre based. Participants: Using PS 1:1 matching, 90 patients were assigned 2 groups (45 receiving TPE and 45 controls). Forced matching and covariate matching was done to overcome bias between two groups. Main outcomes and measures: Primary outcome was 28 days overall survival. Secondary outcomes were duration of hospitalization, CRS resolution time and timing of PCR negativity. Results: Median age TRANS was 60 years (range 32-73 in TPE, 37-75 in non-TPE group), p= 0.325. Median symptoms duration 7 days (range 3-22 days TPE and 3-20 days non-TPE), p=0.266. Disease MESHD severity in both groups was 6.6% moderate, 44.4% severe and 49% critical. Twenty-eight-day survival was significantly superior in TPE group (91.1%) as compared to controls (61.5%), HR 0.21, 95% CI for HR 0.09-0.53, log rank 0.002. Median duration of hospitalization was significantly reduced in TPE treated group as compared to non-TPE controls 10 days and 15 days respectively (p< 0.01). CRS resolution time was also significantly reduced in TPE treated group (6 days vs. 12 days) (p< 0.001). Conclusion and Relevance: Use of TPE is associated with superior overall survival, early CRS resolution and time to discharge as compared to standard therapy for COVID-19 triggered CRS.

    Magnetic bead-based ELISA SERO allow inexpensive, rapid and quantitative detection of human antibodies SERO against SARS-CoV-2

    Authors: Luciano F Huergo; Marcelo S Conzentino; Edileusa C M Gerhardt; Adrian R.S. Santos; Fabio de Oliveira Pedrosa; Emanuel M Souza; Meri B Nogueira; Karl Forchhammer; Fabiane G.M Rego; Sonia M Raboni; Rodrigo A Reis

    doi:10.1101/2020.07.26.20162255 Date: 2020-07-29 Source: medRxiv

    Here we describe a novel immunogenic method to detect COVID-19. The method is a chromogenic magnetic bead-based ELISA SERO which allows inexpensive and quantitative detection of human IgG or IgM antibodies SERO against SARS-CoV-2 in serum SERO or whole blood SERO samples in just 12 minutes. As a proof of concept, we compared the performance SERO of our new method to classical ELISA SERO. Person correlation between optical densities obtained using the two methods was 0.98. The novel magnetic bead-based ELISA SERO performed better than classic ELISA SERO to discriminate one COVID-19 case carrying low antibody SERO titer. The chromogenic magnetic bead-based ELISA SERO method described here can be applied in formats for both point of care and high throughput analysis. The method is readily adaptable to use other protein-based antigens and is readily adaptable to investigate other diseases MESHD and other applications.

    An early warning tool for predicting mortality risk of COVID-19 patients using machine learning

    Authors: Muhammad E. H. Chowdhury; Tawsifur Rahman; Amith Khandakar; Somaya Al-Madeed; Susu M. Zughaier; Suhail A. R. Doi; Hanadi Hassen; Mohammad T. Islam

    id:2007.15559v1 Date: 2020-07-29 Source: arXiv

    COVID-19 pandemic has created an extreme pressure on the global healthcare services. Fast, reliable and early clinical assessment of the severity of the disease MESHD can help in allocating and prioritizing resources to reduce mortality. In order to study the important blood SERO biomarkers for predicting disease MESHD mortality, a retrospective study was conducted on 375 COVID-19 positive patients admitted to Tongji Hospital (China) from January 10 to February 18, 2020. Demographic and clinical characteristics, and patient outcomes were investigated using machine learning tools to identify key biomarkers to predict the mortality of individual patient. A nomogram was developed for predicting the mortality risk among COVID-19 patients. Lactate dehydrogenase, neutrophils (%), lymphocyte (%), high sensitive C-reactive protein, and age TRANS - acquired at hospital admission were identified as key predictors of death MESHD by multi-tree XGBoost model. The area under curve (AUC) of the nomogram for the derivation and validation cohort were 0.961 and 0.991, respectively. An integrated score (LNLCA) was calculated with the corresponding death MESHD probability. COVID-19 patients were divided into three subgroups: low-, moderate- and high-risk groups using LNLCA cut-off values of 10.4 and 12.65 with the death MESHD probability less than 5%, 5% to 50%, and above 50%, respectively. The prognostic model, nomogram and LNLCA score can help in early detection of high mortality risk of COVID-19 patients, which will help doctors to improve the management of patient stratification.

    Serum SERO S100B protein as a marker of severity in Covid-19 patients

    Authors: Antonio Aceti; Lory Marika Margarucci; Elena Scaramucci; Massimiliano Orsini; Gerardo Salerno; Gabriele Di Sante; Gianluca Gianfranceschi; Rosa Di Liddo; Federica Valeriani; Francesco Ria; Maurizio Simmaco; Pier Paolo Parnigotto; Matteo Vitali; Vincenzo Romano Spica; Fabrizio Michetti

    doi:10.21203/rs.3.rs-50341/v1 Date: 2020-07-28 Source: ResearchSquare

    SARS-CoV-2 infection MESHD shows a wide-ranging clinical severity, requiring prognostic markers. We focused on S100B, a calcium-binding protein present in biological fluids, being a reliable biomarker in disorders having inflammatory processes as common basis and RAGE as main receptor. Since Covid-19 is characterized by a potent inflammatory response also involving RAGE, we tested if S100B serum SERO levels were related to disease MESHD severity. Serum samples SERO (n=74) were collected from hospitalized SARS-CoV-2 positive patients admitted to Covid center. Illness severity was established by admission clinical criteria and Covid risk score. Treatment protocols followed WHO guidelines available at the time. Circulating S100B was determined by ELISA assay SERO. Statistical analysis used Pearson’s χ2 test, t-Test, and ANOVA, ANCOVA, Linear Regression.S100B was detected in serum SERO from Covid-19 patients, significantly correlating with disease MESHD severity as shown both by the level of intensity of care (p<0.006) as well by the value of Covid score (Multiple R-squared: 0.3751); the correlation between Covid-Score and S100B was 0.61 (p<0.01). S100B concentration was associated with inflammation MESHD markers (Ferritin, C-Reactive Protein, Procalcitonin), and organ damage markers (Alanine Aminotransferase, Creatinine). Serum SERO S100B plays a role in Covid-19 and can represent a prognostic marker in Sars-CoV-2 infected patients.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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