Corpus overview


Overview

MeSH Disease

Infections (541)

Disease (486)

Coronavirus Infections (322)

Death (187)

Pneumonia (169)


Human Phenotype

Transmission

Seroprevalence
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    Clinical Utility of a Highly Sensitive Lateral Flow Immunoassay SERO as determined by Titer Analysis for the Detection of anti- SARS-CoV-2 Antibodies SERO at the Point-of-Care

    Authors: Amanda Haymond; Claudius Mueller; Hannah Steinberg; K. Alex Hodge; Caitlin W Lehman; Shih-Chao Lin; Lucia Collini; Heather Branscome; Tuong Vi Nguyen; Sally Rucker; Lauren Panny; Rafaela Flor; Raouf Guirguis; Richard Hoefer; Giovanni Lorenzin; Emanuel Petricoin; Fatah Kashanchi; Kylene Kehn-Hall; Paolo Lanzafame; Lance Liotta; Alessandra Luchini

    doi:10.1101/2020.07.30.20163824 Date: 2020-08-02 Source: medRxiv

    Coronavirus disease MESHD 2019 (COVID-19), caused by the severe acute respiratory syndrome MESHD coronavirus-2 (SARS-CoV-2), became a pandemic in early 2020. Lateral flow immunoassays SERO for antibody testing SERO have been viewed as a cheap and rapidly deployable method for determining previous infection MESHD with SARS-CoV-2; however, these assays have shown unacceptably low sensitivity SERO. We report on nine lateral flow immunoassays SERO currently available and compare their titer sensitivity SERO in serum SERO to a best-practice enzyme-linked immunosorbent assay SERO ( ELISA SERO) and viral neutralization assay. For a small group of PCR-positive, we found two lateral flow immunoassay SERO devices with titer sensitivity SERO roughly equal to the ELISA SERO; these devices were positive for all PCR-positive patients harboring SARS-CoV-2 neutralizing antibodies SERO. One of these devices was deployed in Northern Italy to test its sensitivity SERO and specificity in a real-world clinical setting. Using the device with fingerstick blood SERO on a cohort of 27 hospitalized PCR-positive patients and seven hospitalized controls, ROC curve analysis gave AUC values of 0.7646 for IgG. For comparison, this assay was also tested with saliva from the same patient population and showed reduced discrimination between cases and controls with AUC values of 0.6841 for IgG. Furthermore, during viral neutralization testing, one patient was discovered to harbor autoantibodies to ACE2, with implications for how immune responses are profiled. We show here through a proof-of-concept study that these lateral flow devices can be as analytically sensitive as ELISAs SERO and adopted into hospital protocols; however, additional improvements to these devices remain necessary before their clinical deployment.

    Comparison of sixteen serological SARS-CoV-2 immunoassays SERO in sixteen clinical laboratories

    Authors: Lene Holm Harritshoej; Mikkel Gybel-Brask; Shoaib Afzal; Pia R. Kamstrup; Charlotte Svaerke Joergensen; Marianne K. Thomsen; Linda M. Hilsted; Lennart J. Friis-Hansen; Pal B. Szecsi; Lise Pedersen; Lene Nielsen; Cecilie B. Hansen; Peter Garred; Trine-Line Korsholm; Susan Mikkelsen; Kirstine O. Nielsen; Bjarne K. Moeller; Anne T. Hansen; Kasper K. Iversen; Pernille B. Nielsen; Rasmus B. Hasselbalch; Kamille Fogh; Jakob B. Norsk; Jonas H. Kristensen; Kristian Schoenning; Nikolai S. Kirkby; Alex C.Y. Nielsen; Lone H. Landsy; Mette Loftager; Dorte K. Holm; Anna C. Nilsson; Susanne G. Saekmose; Birgitte Grum-Svendsen; Bitten Aagaard; Thoeger G. Jensen; Dorte M. Nielsen; Henrik Ullum; Ram BC Dessau

    doi:10.1101/2020.07.30.20165373 Date: 2020-08-02 Source: medRxiv

    Serological SARS-CoV-2 assays are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for the large-volume detection of total antibodies SERO (Ab) and immunoglobulin (Ig) G and M against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was organized as a Danish national collaboration and included fifteen commercial and one in-house anti-SARS-CoV-2 assays in sixteen laboratories. Sensitivity SERO was evaluated using 150 serum samples SERO from individuals diagnosed with asymptomatic TRANS, mild or moderate nonhospitalized (n=129) or hospitalized (n=31) COVID-19, confirmed by nucleic acid amplification tests, collected 13-73 days from symptom onset TRANS. Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from > 586 blood SERO donors and patients with autoimmune diseases MESHD or CMV or EBV infections MESHD. Predefined specificity criteria of [≥]99% were met by all total-Ab and IgG assays except one (Diasorin/LiaisonXL-IgG 97.2%). The sensitivities SERO in descending order were: Wantai/ ELISA SERO total-Ab (96.7%), CUH/NOVO in-house ELISA SERO total-Ab (96.0%), Ortho/Vitros total-Ab (95.3%), YHLO/iFlash-IgG (94.0%), Ortho/Vitros-IgG (93.3%), Siemens/Atellica total-Ab (93.2%), Roche-Elecsys total-Ab (92.7%), Abbott-Architect-IgG (90.0%), Abbott/Alinity-IgG (median 88.0%), Diasorin/LiaisonXL-IgG (84.6%), Siemens/Vista total-Ab (81.0%), Euroimmun/ ELISA-IgG SERO (78.0%), and Snibe/Maglumi-IgG (median 78.0%). The IgM results were variable, but one assay (Wantai/ ELISA SERO-IgM) had both high sensitivity SERO (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset TRANS and symptom severity. In conclusion, predefined sensitivity SERO and specificity acceptance criteria of 90%/99%, respectively, for diagnostic use were met in five of six total-Ab and three of seven IgG assays.

    Outpatient screening of health status and lifestyle among post-bariatric patients during the Covid-19 pandemic in Sao Paulo, Brazil.

    Authors: Karla Fabiana Goessler; Carolina Ferreira Nicoletti; Diego Augusto Nunes Rezende; Sofia Mendes Sieczkowska; Gabriel Perri Esteves; Rafael Genario; Gersiel Nascimento Oliveira-Junior; Kamila Meireles; Ana Jessica Pinto; Michele Nakahara-Melo; Roberto Cleva; Marco Aurelio Santo; John Kirwan; Hamilton Roschel; Bruno Gualano

    doi:10.1101/2020.07.30.20165068 Date: 2020-08-02 Source: medRxiv

    Background/Objectives: This was an out-of-hospital screening of health status and lifestyle during the Covid-19 pandemic in post-operative bariatric patients from Sao Paulo, Brazil, prevented from face-to-face health care. Subjects/Methods: In this cross-sectional study, 66 patients were remotely (via phone call) and in-person (by home visit) assessed for health status and lifestyle habits. Results: Mean age TRANS was 47.4 years. Patients were obese grade I (30.0%), II (22.0%), and III (30.0%), and 94.2% had above reference waist circumference values. Sixty-four percent displayed high blood SERO pressure, whereas 24% showed CRP levels above normal range. Nineteen percent of patients reported irregular use of nutritional supplementation and 6.0% reported binge eating habits. Thirty-three exhibited symptoms of depression. Mild-to-moderate and moderate-to-severe anxiety HP symptoms were reported by 27.4% and 11.3% of the patients; 4.5% exhibited suicidal ideation HP and were referred to a specialist for healthcare. Of relevance, inactive patients (59.6%) had poorer global mental and physical health scores as compared to active peers (both p<0.05). Conclusion: This out-of-hospital screening revealed that the absence of face-to-face health care due to the Covid-19 pandemic is associated with suboptimal status of physical and mental health as well as lifestyle inadequacies among patients who have recently undergone bariatric surgery.

    High SARS-CoV-2 seroprevalence SERO in Health Care Workers but relatively low numbers of deaths MESHD in urban Malawi

    Authors: Marah Grace Chibwana; Khuzwayo Chidiwa Jere; Jonathan Mandolo; Vincent Katunga-Phiri; Dumizulu Tembo; Ndaona Mitole; Samantha Musasa; Simon Sichone; Agness Lakudzala; Lusako Sibale; Prisca Matambo; Innocent Kadwala; Rachel Louise Byrne; Alice Mbewe; Ben Morton; Chimota Phiri; Jane Mallewa; Henry C Mwandumba; Emily R Adams; Stephen B Gordon; Kondwani Charles Jambo

    doi:10.1101/2020.07.30.20164970 Date: 2020-08-01 Source: medRxiv

    Background In low-income countries, like Malawi, important public health measures including social distancing or a lockdown, have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD, there are no reliable estimates of the true burden of infection MESHD and death MESHD. We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers (HCW) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection MESHD in urban Malawi. Methods Five hundred otherwise asymptomatic TRANS HCWs were recruited from Blantyre City (Malawi) from 22nd May 2020 to 19th June 2020 and serum samples SERO were collected all participants. A commercial ELISA SERO was used to measure SARS-CoV-2 IgG antibodies SERO in serum SERO. We run local negative samples (2018 - 2019) to verify the specificity of the assay. To estimate the seroprevalence SERO of SARS CoV-2 antibodies SERO, we adjusted the proportion of positive results based on local specificity of the assay. Results Eighty-four participants tested positive for SARS-CoV-2 antibodies SERO. The HCW with a positive SARS-CoV-2 antibody SERO result came from different parts of the city. The adjusted seroprevalence SERO of SARS-CoV-2 antibodies SERO was 12.3% [CI 9.0-15.7]. Using age TRANS-stratified infection MESHD fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence SERO, the number of predicted deaths MESHD was 8 times the number of reported deaths MESHD. Conclusion The high seroprevalence SERO of SARS-CoV-2 antibodies SERO among HCW and the discrepancy in the predicted versus reported deaths MESHD, suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.

    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.

    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.

    Sex-specificity of mortality risk factors among hospitalized COVID-19 patients in New York City: prospective cohort study

    Authors: Tomi Jun; Sharon Nirenberg; Patricia Kovatch; Kuan-lin Huang

    doi:10.1101/2020.07.29.20164640 Date: 2020-08-01 Source: medRxiv

    Objective: To identify sex-specific effects of risk factors for in-hospital mortality among COVID-19 patients admitted to a hospital system in New York City. Design: Prospective observational cohort study with in-hospital mortality as the primary outcome. Setting: Five acute care hospitals within a single academic medical system in New York City. Participants: 3,086 hospital inpatients with COVID-19 admitted on or before April 13, 2020 and followed through June 2, 2020. Follow-up till discharge or death MESHD was complete for 99.3% of the cohort. Results: The majority of the cohort was male TRANS (59.6%). Men were younger (median 64 vs. 70, p<0.001) and less likely to have comorbidities such as hypertension MESHD hypertension HP (32.5% vs. 39.9%, p<0.001), diabetes (22.6% vs. 26%, p=0.03), and obesity MESHD obesity HP (6.9% vs. 9.8%, p=0.004) compared to women. Women had lower median values of laboratory markers associated with inflammation MESHD compared to men: white blood SERO cells (5.95 vs. 6.8 K/uL, p<0.001), procalcitonin (0.14 vs 0.21 ng/mL, p<0.001), lactate dehydrogenase (375 vs. 428 U/L, p<0.001), C-reactive protein (87.7 vs. 123.2 mg/L, p<0.001). Unadjusted mortality was similar between men and women (28.8% vs. 28.5%, p=0.84), but more men required intensive care than women (25.2% vs. 19%, p<0.001). Male TRANS sex was an independent risk factor for mortality (OR 1.26, 95% 1.04-1.51) after adjustment for demographics, comorbidities, and baseline hypoxia MESHD. There were significant interactions between sex and coronary artery disease MESHD (p=0.038), obesity MESHD obesity HP (p=0.01), baseline hypoxia MESHD (p<0.001), ferritin (p=0.002), lactate dehydrogenase (p=0.003), and procalcitonin (p=0.03). Except for procalcitonin, which had the opposite association, each of these factors was associated with disproportionately higher mortality among women. Conclusions: Male TRANS sex was an independent predictor of mortality, consistent with prior studies. Notably, there were significant sex-specific interactions which indicated a disproportionate increase in mortality among women with coronary artery disease MESHD, obesity MESHD obesity HP, and hypoxia MESHD. These new findings highlight patient subgroups for further study and help explain the recognized sex differences in COVID-19 outcomes.

    Converting Microwave Ovens into Plasma SERO-Generating Decontamination Units for N-95 Respirators

    Authors: David N. Ruzic; Chamteut Oh; Joseph V. Puthussery; Vishal Verma; Thanh H. Nguyen

    doi:10.1101/2020.07.28.20163915 Date: 2020-07-31 Source: medRxiv

    We show how a common microwave oven, a coat-hanger and a coffee cup can be used to decontaminate N-95 respirators in 30 seconds. Tulane virus in artificial saliva was reduced by >3 log and Geobacillus stearothermophilus spores were reduced by >6 log. Respirators maintained filtration and fitting after 10 cycles.

    SARS-CoV-2 protein subunit vaccination elicits potent neutralizing antibody SERO responses

    Authors: Marco Mandolesi; Daniel J Sheward; Leo Hanke; Junjie Ma; Pradeepa Pushparaj; Laura Perez Vidakovics; Changil Kim; Karin Loré; Xaquin Castro Dopico; Jonathan M Coquet; Gerald McInerney; Gunilla B Karlsson Hedestam; Ben Murrell

    doi:10.1101/2020.07.31.228486 Date: 2020-07-31 Source: bioRxiv

    The outbreak and spread of SARS-CoV-2 ( Severe Acute Respiratory Syndrome MESHD coronavirus 2), the cause of coronavirus disease MESHD 2019 (COVID-19), is a current global health emergency MESHD and a prophylactic vaccine is needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is a target for neutralizing antibodies SERO and vaccine design. Here we show that adjuvanted protein immunization with SARS-CoV-2 spike trimers, stabilized in prefusion conformation 1, results in potent antibody SERO responses in mice and rhesus macaques with neutralizing antibody SERO titers orders of magnitude greater than those typically measured in serum SERO from SARS-CoV-2 seropositive humans. Neutralizing antibody SERO responses were observed after a single dose, with exceptionally high titers achieved after boosting. Furthermore, neutralizing antibody SERO titers elicited by a dose-sparing regimen in mice were similar to those obtained from a high dose regimen. Taken together, these data strongly support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.

    Red blood SERO cells injuries and hypersegmented neutrophils in COVID-19 peripheral blood SERO film

    Authors: Nordine Lakhdari; Boualem Tabet; Lila Boudraham; Malha Laoussati; Sofiane Aissanou; Lamia Beddou; Sihem Bensalem; Yuva Bellik; Lamine Bournine; Sofiane Fatmi; Mokrane Iguer-Ouada

    doi:10.1101/2020.07.24.20160101 Date: 2020-07-30 Source: medRxiv

    In the current investigation, peripheral blood SERO films of 15 COVID-19 patients (44.78{+/-}16.55 years), proven by computed tomographic imaging and RT-PCR for coronavirus SARS-CoV-2, were analyzed at the moment of hospital admission. Blood SERO tests showed raised inflammatory markers (C-reactive protein 58.2{+/-}61.2 mg/L) with normal values for hemoglobin (126.2{+/-}2.6 g/L), WBC (6.8{+/-}18.74 109/L) RBC (4.55{+/-}0.99 1012/L) platelets (262.4{+/-}41.8, 109/L) MCV (79.84{+/-}8.2 fL) MCH (28{+/-}3.31 pg) and MCHC (350.3{+/-}1.15 g/L). The results revealed the presence of hypersegmented neutrophils in 66.66%% of the patients. The percentages of neutrophils with 4 and 5 lobes were 46.25{+/-}4.83% and 31.5{+/-}14.84%, respectively. Three major red blood SERO cells morphological alteration were observed: (1) erythrocytes in double primerouleauxdouble prime formation represented by linear erythrocytes aggregation, (2) spherocytes with the disappearance of the usual biconcave disk, and (3) echinocytes showing spiky projections. Apparent reorganization of hemoglobin is found in the majority of the analyzed erythrocytes. Rouleaux formation HP is observed in 33.33% of patients and spherocytes and echinocytes are present at variable levels in the all analyzed patients. The current results revealed erythrocytes injuries in COVID-19 peripheral blood SERO, in association with hypersegmented neutrophils, alterations that could be involved in the respiratory syndrome MESHD.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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