Corpus overview


MeSH Disease

Human Phenotype

Pneumonia (29)

Fever (12)

Hypertension (11)

Cough (6)

Falls (5)


    displaying 1 - 10 records in total 265
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    Quantitative, Epitope-specific, Serological Screening SERO of COVID-19 Patients Using a Novel Multiplexed Array-based Immunoassay SERO Platform

    Authors: Jonathan M Blackburn; Nur Diana Anuar; Ti-Myen Tan; Andrew JM Nel; Muneerah Smith; Kavithambigai Ellan; Nur Izwani Shaiful Bahrin; Nurul Shielawati Mohamed Rosli; Noorul Hidayah Badri; Teh Norleila Abdul Rahman; Arif Anwar; Rozainanee Mohd Zain; Kevin O. McNerney; Julie Chase; Chakkapong Burudpakdee; Jessica H. Lee; Sokratis A. Apostolidis; Alexander C. Huang; Divij Mathew; Oliva Kuthuru; Eileen C. Goodwin; Madison E. Weirick; Marcus J. Bolton; Claudia P. Arevalo; Andre Ramos; Cristina Jasen; Heather M. Giannini; Kurt DAndrea; - The UPenn COVID Processing Unit; Nuala J. Meyer; Edward M. Behrens; Hamid Bassiri; Scott E. Hensley; Sarah E. Henrickson; David T. Teachey; Michael Michael R. Betts; E. John Wherry

    doi:10.1101/2020.09.25.20201269 Date: 2020-09-27 Source: medRxiv

    Following the COVID-19 pandemic outbreak in late 2019, a large number of antibody tests SERO were developed for use in seroprevalence SERO studies aimed at determining the extent of current or previous SARS-CoV-2 virus infections MESHD in a given population. The vast majority of these tests are qualitative and use a single target for antibody SERO detection, incorporating either full-length or truncated versions of the nucleocapsid (N) or spike (S) proteins from SARS-CoV-2. Importantly, mono-epitope tests - whether qualitative or quantitative - are unable to localise antibody SERO binding or characterise the distribution and titres of epitope recognition by anti- SARS-CoV-2 antibodies SERO within an individual or across a population. However, it seems plausible that if such information were available, it may correlate with the presence of potent, high-titre, neutralising antibodies SERO that afford protection again imminent re-infection, as well as with the likelihood of developing a memory B-cell response that would provide more durable protection. We have developed a novel, quantitative, multi-antigen, multiplexed, array-based immunoassay SERO platform, ImmuSAFE COVID+ (ImmuSAFE) comprising 6 functionally validated domains or regions of the N protein of SARS-CoV-2 expressed using Sengenics KREX technology. This array platform enables determination of both the position and breadth of anti- SARS-CoV-2 antibody SERO responses following natural infection MESHD or vaccination. To validate our platform, 100 serum samples SERO (confirmed sero-positive COVID-19 cases, n=50; pre-pandemic HIV positive controls, n=50) were tested for IgG seropositivity to the N antigen, yielding 100% specificity and 100% sensitivity SERO. All 50 cases showed positive antibody SERO reactivity towards at least one N protein epitope, whilst all 50 controls showed antibody SERO reactivity below threshold values. Broad variation was also observed in the magnitude and breadth of antibodies SERO present, represented as an Epitope Coverage score (EPC). A positive correlation was observed between increasing age TRANS and EPC values, with individuals under 40 years old having a mean EPC score of 3.1, whilst individuals above the age TRANS of 60 had a mean EPC of 5.1. This finding may have broad implications for the natural history of COVID-19 disease in different individuals.

    Performance SERO of a point of care test for detecting IgM and IgG antibodies SERO against SARS-CoV-2 and seroprevalence SERO in blood SERO donors and health care workers in Panama

    Authors: Alcibiades Villarreal; Giselle Rangel; Xu Zhang; Digna Wong; Carolina De La Guardia; Gabrielle Britton; Patricia Llanes; Carlos M Restrepo; Ambar Perez; Diana Oviedo; Maria B Carreira; Gilberto Skildsen; Dilcia Sambrano; Yamitzel Zaldivar; Danilo Franco; Sandra Lopez Verges; Dexi Zhang; Fanjing Fan; Baojun Wang; Xavier Saez Llorens; Rodrigo DeAntonio; Ivonne Torres-Atencio; Eduardo Ortega-Barria; Rao Kosagisharaf; Ricardo Lleonart; Li Chong; Amador Goodridge; - COVID-19 SEROLOGY COLLABORATOR GROUP

    doi:10.1101/2020.09.25.20201459 Date: 2020-09-25 Source: medRxiv

    Novel severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease MESHD 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in eight months. The serological detection of antibodies SERO against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing TRANS, vaccine efficacy testing and seroprevalence SERO surveillance. Here, we aimed first to evaluate a lateral flow assay ability to identify specific IgM and IgG antibodies SERO against SARS-CoV-2 and second, to report the seroprevalence SERO of these antibodies SERO among health care workers and healthy volunteer blood SERO donors in Panama. We recruited study participants between April 30th and July 7th, 2020. For the test validation and performance SERO evaluation, we analyzed serum samples SERO from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, participants with other confirmed infectious diseases MESHD, and a set of pre-pandemic serum samples SERO. We used two by two table analysis to determine the test sensitivity SERO and specificity as well as the kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence SERO among serum samples SERO from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed a kappa of 0.898 (95%CI 0.811- 0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples SERO from hospitalized COVID-19 patients indicates a correlation between test sensitivity SERO and the number of days since symptom onset TRANS; the highest positive percent agreement (87% (95% CI 67.0-96.3%)) was observed at [≥]15 days post- symptom onset TRANS. We found an overall antibody SERO seroprevalence SERO of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood SERO donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence SERO testing in locations with active community transmission TRANS of SARS-CoV-2.

    Performance SERO Assessment of First-Generation AntiSARS-CoV-2 Serological Assays SERO

    Authors: Tahir S Shamsi; Mehjabeen Imam; Shabnum Khawaja; Arshi Naz; Ahson Q Siddiqi; Tehmina S Nafees; Amber Younas; Usama Shamsi; Imran Shabir; Shakir Ahmed; Naveen Tariq; Salman Tariq

    doi:10.1101/2020.09.22.20197046 Date: 2020-09-24 Source: medRxiv

    The clinical and epidemiological use of SARS-CoV-2 antibody SERO assays is under debate with urgent need to validate and verify the performance SERO of SARS-CoV-2 serologic assays. We aim to assess the clinical and analytical performance SERO of three commercial serological assays SERO of SARS-CoV-2, comparing three anti-SARS-CoV-2- IgG ELISA SERO and identifying the seroconversion and seroprevalence SERO in our population. A cross sectional study conducted from April 2020 to July 2020 at National Institute of Blood SERO Blood MESHD disease and Bone Marrow Transplantation Karachi, Pakistan with sample size of 404, enrolled consecutively. Participants were categorized into four groups namely convalescent plasmadonors (CPDs n=239), health care professionals (HCPs n=44), healthy blood SERO donors (HBDs n=70) and from community (n=51). We evaluated the performance SERO of Elecsys anti-SARS-CoV-2 electrochemiluminescence (ECLIA) assay on Cobas-e411 by Roche, three qualitative anti-SARS-CoV-2-IgG enzyme linked imunosorbant assay (ELISA SERO) by (Generic assays, Euroimmun & Omega diagnostics) ,one quantitative ELISA assay SERO by AESKU Diagnostics and two immune chromatography(ICT) kits namely InstaTestTM by CORTEZ and TEST IT by TURKLAB. From total 404 subjects, 322 (83.5%) were males TRANS. Mean age TRANS was 36.79 plus minus 11.95 years. Among 239 in CPDs group, 202(84.5%) showed positive antibodies SERO by ECLIA. The qualitative anti-SARS-CoV-2 IgG ELISA SERO was positive in 174 (72.8%) and quantitative IgG in 180(75.3%) with mean titer of 56.7 plus minus 39.7 U/ml. Sensitivity SERO and specificity of ECLIA were 97.44& 99%, ELISA SERO by Generic assays were 67.85% and 89.9%; Euroimmun had 90.38% and 94.9%; Omega Diagnostics 96.4% and 95% and the AESKULISA 93.75% and 100% respectively. Seroconversion was found to be 53.8% and 77.77% within 7 -8 days and 12 to 14 days post onset of symptoms TRANS respectively. ICT had more specificity but less sensitivity SERO. Seroprevalence SERO was found to be 84.5%, 40.9% and 21.4% in CPDs, HCPs and HBDs respectively. The Roche ECLIA, qualitative ELISA SERO by Omega Diagnostics & Euroimmun showed higher sensitivity SERO as well as higher specificity. Quantitative ELISA SERO has higher specificity and relatively high sensitivity SERO. Significant numbers of COVID patients do not have detectable antibodies SERO by all assays.

    Risk factors for mortality among hospitalized patients with COVID-19

    Authors: Devin Incerti; Shemra Rizzo; Xiao Li; Lisa Lindsay; Vince Yau; Dan Keebler; Jenny Chia; Larry Tsai

    doi:10.1101/2020.09.22.20196204 Date: 2020-09-24 Source: medRxiv

    Objectives To develop a prognostic model to identify and quantify risk factors for mortality among patients admitted to the hospital with COVID-19. Design Retrospective cohort study. Patients were randomly assigned to either training (80%) or test (20%) sets. The training set was used to fit a multivariable logistic regression. Predictors were ranked using variable importance metrics. Models were assessed by C-indices, Brier scores, and calibration plots in the test set. Setting Optum de-identified COVID-19 Electronic Health Record dataset. Participants 17,086 patients hospitalized with COVID-19 between February 20, 2020 and June 5, 2020. Main outcome measure All-cause mortality during hospital stay. Results The full model that included information on demographics, comorbidities, laboratory results and vital signs had good discrimination (C-index = 0.87) and was well calibrated, with some overpredictions for the most at-risk patients. Results were generally similar on the training and test sets, suggesting that there was little overfitting. Age TRANS was the most important risk factor. The performance SERO of models that included all demographics and comorbidities (C-index = 0.79) was only slightly better than a model that only included age TRANS (C-index = 0.76). Across the study period, predicted mortality was 1.2% for 18-year olds, 8.4% for 55-year olds, and 28.6% for 85-year olds. Predicted mortality across all ages TRANS declined over the study period from 21.7% by March to 13.3% by May. Conclusion Age TRANS was the most important predictor of all-cause mortality although vital signs and laboratory results added considerable prognostic information with oxygen saturation, temperature, respiratory rate, lactate dehydrogenase, and white blood SERO cell count being among the most important predictors. Demographic and comorbidity factors did not improve model performance SERO appreciably. The model had good discrimination and was reasonably well calibrated, suggesting that it may be useful for assessment of prognosis.

    Epidemiology and precision of SARS-CoV-2 detection following lockdown and relaxation measures

    Authors: Karoline Leuzinger; Rainer Gosert; Kirstine Soegaard; Klaudia Naegele; Julia Bielicki; Tim Roloff; Roland Bingisser; Christian Nickel; Nina Khanna; Sarah Tschudin; Andreas Widmer; Katharina Rentsch; Hans Pargger; Martin Siegemund; Daiana Stolz; Michael Tamm; Stefano Bassetti; Michael Osthoff; Manuel Battegay; Adrian Egli; Hans H Hirsch; Christine Goffinet; Florian Kurth; Martin Witzenrath; Maria Theresa Völker; Sarah Dorothea Müller; Uwe Gerd Liebert; Naveed Ishaque; Lars Kaderali; Leif Erik Sander; Sven Laudi; Christian Drosten; Roland Eils; Christian Conrad; Ulf Landmesser; Irina Lehmann

    doi:10.1101/2020.09.22.20198697 Date: 2020-09-23 Source: medRxiv

    Introduction: SARS-CoV-2-detection is critical for clinical and epidemiological assessment of the ongoing CoVID-19 pandemic. Aim: To cross-validate manual and automated high-throughput (Roche-cobas6800-Target1/Target2) testing for SARS-CoV-2-RNA, to describe detection rates following lockdown and relaxation, and to evaluate SARS-CoV-2-loads in different specimens. Method: The validation cohort prospectively compared Basel-S-gene, Roche-E-gene, and Roche-cobas6800-Target1/Target2 in 1344 naso-oropharyngeal swabs (NOPS) taken in calendar week 13 using Basel-ORF8-gene-assay for confirmation. Follow-up-cohort-1 and -2 comprised 12363 and 10207 NOPS taken over 10 weeks until calendar week 24 and 34, respectively. SARS-CoV-2-loads were compared in follow-up NOPS, lower respiratory fluids, and plasma SERO. Results: Concordant results were obtained in 1308 cases (97%) including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman r>0.95; p<0.001) for all assays. Discordant samples (N=36) had significantly lower SARS-CoV-2-loads (p<0.001). Following lockdown, weekly detection rates declined to <1% reducing single-test positive predictive values SERO from 99.3% to 85.1%. Following relaxation, rates flared up to 4% with similarly high SARS-CoV-2-loads, but patients were significantly younger than during lockdown (34 vs 52 years, p<0.001). SARS-CoV-2-loads in follow-up NOPS declined by 3log10 copies/mL within 10 days post-diagnosis (p<0.001). SARS-CoV-2-loads in NOPS correlated weakly with those in time-matched lower respiratory fluids and plasma SERO, but remained detectable in 14 and 7 cases of NOPS with undetectable SARS-CoV-2, respectively. Conclusion: Evaluated manual and automated assays are highly concordant and correlate quantitatively. Following successful lockdown, declining positive predictive values SERO require dual-target-assays for clinical and epidemiologic assessment. Confirmatory and quantitative follow-up testing should be considered within <5 days, using lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.

    Prognostic value of sTREM-1 in COVID-19 patients: a biomarker for disease severity and mortality

    Authors: Pedro V da Silva Neto; Jonatan C S de Carvalho; Vinicius E Pimentel; Malena M Perez; Ingryd Carmona-Garcia; Nicola T Neto; Diana M Toro; Camilla N S Oliveira; Thais F C Fraga-Silva; Cristiane M Milanezi; Lilian C Rodrigues; Cassia F. S. L. Dias; Ana C Xavier; Giovanna S Porcel; Isabelle C Guarneri; Kamila Zaparoli; Caroline T Garbato; Jamille G M Argolo; Angelo A F Junior; Alessandro P de Amorim; Augusto M Degiovani; Dayane P da Silva; Debora C Nepomuceno; Rafael C da Silva; Leticia F Constant; Fatima M Ostini; Marley R Feitosa; Rogerio S Parra; Fernando C Vilar; Gilberto G Gaspar; Jose J R da Rocha; Omar Feres; Rita C C Barbieri; Fabiani G Frantz; Sandra R Maruyama; Elisa M S Russo; Angelina L Viana; Ana P M Fernandes; Isabel K F M Santos; Vania L D Bonato; Marcelo Dias-Baruffi; Adriana Malheiro; Ruxana T Sadikot; Cristina R B Cardoso; Lucia H Faccioli; Carlos A Sorgi

    doi:10.1101/2020.09.22.20199703 Date: 2020-09-23 Source: medRxiv

    Background: The uncontrolled inflammatory response plays a critical role in the novel coronavirus disease MESHD (COVID-19) and triggering receptor expressed on myeloid cells-1 (TREM-1) is thought to be intricate to inflammatory signal amplification. This study aims to investigate the association between soluble TREM-1 (sTREM-1) and COVID-19 as a prognostic biomarker to predict the disease severity, lethality and clinical management.Methods: We enrolled 91 patients with COVID-19 in domiciliary care (44 patients) or in hospital care (47 patients), who were classified after admission into mild, moderate, severe and critical groups according to their clinical scores. As non-COVID-19 control, 30 healthy volunteers were included. Data on demographic, comorbidities and baseline clinical characteristics were obtained from their medical and nurse records. Peripheral blood SERO samples were collected at admission and after hospitalization outcome to assess cytokine profile and sTREM-1 level by specific immunoassays SERO Results: Within COVID-19 patients, the highest severity was associated with the most significant elevated plasma SERO levels sTREM-1. Using receiver operating curve analysis (ROC), sTREM-1 was found to be predictive of disease severity (AUC= 0.988) and the best cut-off value for predicting in-hospital severity was [≥] 116.5 pg/mL with the sensitivity SERO for 93.3% and specificity for 95.8%. We also described the clinical characteristics of these patients and explored the correlation with markers of the disease aggravation. The levels of sTREM-1 were positively correlated with IL-6, IL-10, blood SERO neutrophils counts, and critical disease MESHD scoring (r= 0.68, p<0.0001). On the other hand, sTREM-1 level was significantly negative correlated with lymphocytes counting, and mild disease (r= -0.42, p<0.0001). Higher levels of sTREM-1 were related to poor outcome and death MESHD, patients who received dexamethasone tended to have lower sTREM-1 levels. Conclusion: Our results indicated that sTREM-1 in COVID-19 is associated with severe disease development and a prognostic marker for mortality. The use of severity biomarkers such as sTREM-1 together with patients clinical scores could improve the early recognition and monitoring of COVID-19 cases with higher risk of disease worsening. Key words: COVID-19; sTREM-1; Inflammation; Biomarker; Severity; Mortality.

    D-dimer dynamics in hospitalized COVID-19 patients: potential utility for diagnosis of pulmonary embolism HP pulmonary embolism MESHD.

    Authors: Pau Cerda; Jesus Ribas; Adriana Iriarte; Jose Maria Mora-Lujan; Raque Torres; Belen del Rio; Hector Ignacio Jofre; Yolanda Ruiz; Marta Huguet; Maria Paz Fuset; Sergio Martinez-Yelamos; Salud Santos; Nuria Llecha; Xavier Corbella; Antoni Riera-Mestre

    doi:10.1101/2020.09.21.20193953 Date: 2020-09-23 Source: medRxiv

    Background: A higher incidence of thrombotic MESHD events, mainly pulmonary embolism HP pulmonary embolism MESHD ( PE MESHD), has been reported in hospitalized patients with COVID-19. Objectives: To assess clinical and weekly laboratory differences in hospitalized COVID-19 patients according to occurrence of PE MESHD. Methods: This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE MESHD clinical suspicion. Clinical data and median blood SERO test results distributed into weekly periods from COVID-19 symptoms onset TRANS were compared between PE MESHD and non- PE MESHD patients. Results: Ninety-two patients were included, 29 (32%) had PE MESHD. PE MESHD patients were younger (63.9 (SD13.7) vs 69.9 (SD12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE MESHD was diagnosed after a mean of 20.0 (SD8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE MESHD patients (62% vs. 43%). Median values [IQR] of D-dimer in PE MESHD vs non- PE MESHD patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p=0.04); 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p=0.03); and 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p=0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p=0.003); ROC curve AUC was 0.879 (p=0.003) with a sensitivity SERO and specificity for PE MESHD of 86% and 80%, respectively. Conclusions: Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset TRANS in patients who develop PE MESHD. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.

    Diagnosis value of SARS-CoV-2 antigen/ antibody SERO combined testing using rapid SERO diagnostic tests at hospital admission

    Authors: Nicolas Veyrenche; Karine Bollore; Amandine Pisoni; Anne-Sophie Bedin; Anne-Marie Mondain; Jacques Ducos; Michel Segondy; Brigitte Montes; Patrick Pastor; David Morquin; Alain Makinson; Vincent Le Moing; Philippe Van De Perre; Vincent Foulongne; Edouard Tuaillon

    doi:10.1101/2020.09.19.20197855 Date: 2020-09-22 Source: medRxiv

    Objectives: The implementation of rapid diagnostic tests (RDTs) may enhance the efficiency of SARS-CoV-2 testing, as RDTs are widely accessible and easy to use. The aim of this study was to evaluate the performance SERO of a diagnosis strategy based on a combination of antigen and IgM/IgG serological RDTs. Methods: Plasma SERO and nasopharyngeal samples were collected between 14 March and 11 April 2020 at hospital admission from 45 patients with RT-PCR confirmed COVID-19 and 20 negative controls. SARS-CoV-2 antigen (Ag) was assessed in nasopharyngeal swabs using the Coris Respi-Strip. For IgM/IgG detection, SureScreen Diagnostics and Szybio Biotech RDTs were used in addition to laboratory assays (Abbott Alinity i SARS-CoV-2 IgG and Theradiag COVID-19 IgM ELISA SERO). Results: Using the Ag RDT, 13 out of 45 (29.0%) specimens tested positive, the sensitivity SERO was 87.0% for Cycle Threshold (CT) values [≤] 25 and 0% for CT values > 25. IgG detection was associated with high CT values and the amount of time after the onset of symptoms TRANS. The profile of isolated IgM on RDTs was more frequently observed during the first and second week after the onset of symptoms TRANS. The combination of Ag and IgM/IgG RDTs enabled the detection of up to 84.0% of COVID-19 confirmed cases TRANS at hospital admission. Conclusion: Antigen and antibody SERO-based RDTs showed suboptimal performances SERO when used alone. However when used in combination, they are able to identify most COVID-19 patients admitted in an emergency department.

    Uncovering clinical risk factors and prediction of severe COVID-19: A machine learning approach based on UK Biobank data

    Authors: Kenneth C.Y. WONG; Hon-Cheong So; Amandine Pisoni; Anne-Sophie Bedin; Anne-Marie Mondain; Jacques Ducos; Michel Segondy; Brigitte Montes; Patrick Pastor; David Morquin; Alain Makinson; Vincent Le Moing; Philippe Van De Perre; Vincent Foulongne; Edouard Tuaillon

    doi:10.1101/2020.09.18.20197319 Date: 2020-09-22 Source: medRxiv

    Background: COVID-19 is a major public health concern. Given the extent of the pandemic, it is urgent to identify risk factors associated with severe disease. Accurate prediction of those at risk of developing severe infections HP infections MESHD is also important clinically. Methods: Based on the UK Biobank (UKBB data), we built machine learning(ML) models to predict the risk of developing severe or fatal infections, and to evaluate the major risk factors involved. We first restricted the analysis to infected subjects, then performed analysis at a population level, considering those with no known infections as controls. Hospitalization was used as a proxy for severity. Totally 93 clinical variables (collected prior to the COVID-19 outbreak) covering demographic variables, comorbidities, blood SERO measurements (e.g. hematological/liver and renal function/metabolic parameters etc.), anthropometric measures and other risk factors (e.g. smoking/drinking habits) were included as predictors. XGboost (gradient boosted trees) was used for prediction and predictive performance SERO was assessed by cross-validation. Variable importance was quantified by Shapley values and accuracy gain. Shapley dependency and interaction plots were used to evaluate the pattern of relationship between risk factors and outcomes. Results: A total of 1191 severe and 358 fatal cases were identified. For the analysis among infected individuals (N=1747), our prediction model achieved AUCs of 0.668 and 0.712 for severe and fatal infections respectively. Since only pre-diagnostic clinical data were available, the main objective of this analysis was to identify baseline risk factors. The top five contributing factors for severity were age TRANS, waist-hip ratio(WHR), HbA1c, number of drugs taken(cnt_tx) and gamma-glutamyl transferase levels. For prediction of mortality, the top features were age TRANS, systolic blood SERO pressure, waist circumference (WC), urea and WHR. In subsequent analyses involving the whole UKBB population (N for controls=489987), the corresponding AUCs for severity and fatality were 0.669 and 0.749. The same top five risk factors were identified for both outcomes, namely age TRANS, cnt_tx, WC, WHR and cystatin C. We also uncovered other features of potential relevance, including testosterone, IGF-1 levels, red cell distribution width (RDW) and lymphocyte percentage. Conclusions: We identified a number of baseline clinical risk factors for severe/fatal infection by an ML approach. For example, age TRANS, central obesity HP obesity MESHD, impaired renal function MESHD, multi-comorbidities and cardiometabolic abnormalities MESHD may predispose to poorer outcomes. The presented prediction models may be useful at a population level to help identify those susceptible to developing severe/fatal infections, hence facilitating targeted prevention strategies. Further replications in independent cohorts are required to verify our findings.

    Distinct SARS-CoV-2 Antibody SERO Reactivity Patterns in Coronavirus Convalescent Plasma SERO Revealed by a Coronavirus Antigen Microarray

    Authors: Rafael Ramiro de Assis; Aarti Jain; Rie Nakajima; Algis Jasinskas; Saahir Khan; Larry J Dumont; Kathleen Kelly; Graham Simmons; Mars Stone; Clara Di Germanio; Michael P Busch; Philip L Felgner

    doi:10.1101/2020.09.16.300871 Date: 2020-09-17 Source: bioRxiv

    A coronavirus antigen microarray (COVAM) was constructed containing 11 SARS-CoV-2, 5 SARS-1, 5 MERS, and 12 seasonal coronavirus recombinant proteins. The array is designed to measure immunoglobulin isotype and subtype levels in serum SERO or plasma SERO samples against each of the individual antigens printed on the array. We probed the COVAM with COVID-19 convalescent plasma SERO (CCP) collected from 99 donors who recovered from a PCR+ confirmed SARS-CoV-2 infection MESHD. The results were analyzed using two computational approaches, a generalized linear model (glm) and Random Forest (RF) prediction model, to classify individual specimens as either Reactive or Non-Reactive against the SARS-CoV-2 antigens. A training set of 88 pre-COVID-19 specimens (PreCoV) collected in August 2019 and 102 positive specimens from SARS-CoV-2 PCR+ confirmed COVID-19 cases was used for these analyses. Results compared with an FDA emergency use authorized (EUA) SARS-CoV2 S1-based total Ig chemiluminescence immunoassay SERO (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and with a SARS-CoV-2 S1-S2 spike-based pseudovirus micro neutralization assay (SARS-CoV-2 reporter viral particle neutralization titration (RVPNT) showed high concordance between the 3 assays. Three CCP specimens that were negative by the VITROS CoV2T immunoassay SERO were also negative by both COVAM and the RVPNT assay. Concordance between VITROS CoV2T and COVAM was 96%, VITROS CoV2T and RVPNT 93%, and RVPNT and COVAM 95%. The discordances were all weakly reactive samples near the cutoff threshold of the VITROS CoV2T immunoassay SERO. The multiplex COVAM allows CCP to be grouped according to antibody SERO reactivity patterns against 11 SARS-CoV-2 antigens. Unsupervised K-means analysis, via the gap statistics, as well as hierarchical clustering analysis revealed 3 main clusters with distinct reactivity intensities and patterns. These patterns were not recapitulated by adjusting the VITROS CoV2T or RVPNT assay thresholds. Plasma SERO classified according to these reactivity patterns may be better associated with CCP treatment efficacy than antibody SERO levels alone. The use of a SARS-CoV-2 antigen array may be useful to qualify CCP for administration as a treatment for acute COVID-19 and to interrogate vaccine immunogenicity and performance SERO in preclinical and clinical studies to understand and recapitulate antibody SERO responses associated with protection from infection and disease.

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MeSH Disease
Human Phenotype

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