Corpus overview


MeSH Disease

Human Phenotype

Pneumonia (31)

Fever (23)

Cough (11)

Anosmia (10)

Respiratory distress (10)


    displaying 1 - 10 records in total 449
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    Kinetics of SARS-CoV-2 Antibody SERO Avidity Maturation and Association with Disease MESHD Severity

    Authors: Yiqi Ruben Luo; Indrani Chakraborty; Cassandra Yun; Alan H.B. Wu; Kara Lake Lynch

    doi:10.1101/2020.07.30.20165522 Date: 2020-08-02 Source: medRxiv

    The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD was studied. The IgG avidity assay used a novel label-free immunoassay SERO technology to test IgG against the virus spike protein receptor-binding domain (RBD). The technology, thin-film interferometry (TFI), is able to sense the formation of immune complex on a sensing probe without attaching a reporter (enzyme, fluorophore, etc.). It was found that there was a strong correlation between IgG antibody SERO avidity and days since symptom onset TRANS (p < 0.0001). In addition, peak readings were significantly higher for specimens from ICU than non-ICU patients for the first month after symptom onset TRANS (1-4 weeks) and thereafter (p<0.0001). The findings are consistent for what has been reported for SARS-CoV. Given that SARS-CoV-2 specific IgG avidity is strong in ICU patients after 1 month, this suggests that antibody SERO-mediated immune enhancement triggered by suboptimal antibodies SERO may not play a role in COVID-19 disease progression MESHD and severity.

    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.

    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.

    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.

    Augmentation of anti-MDA5 antibody SERO implies severe disease MESHD in COVID-19 patients

    Authors: Changzheng Liu; Qian Wang; Yeming Wang; Geng Wang; Linghang Wang; Hong Chen; Tao Jiao; Chaojun Hu; Xiaobo Lei; Li Guo; Lili Ren; Mengtao Li; Xiaofeng Zeng; Dingyu Zhang; Bin Cao; Jianwei Wang

    doi:10.1101/2020.07.29.20164780 Date: 2020-08-01 Source: medRxiv

    Recent studies have provided insights into the autoinflammation triggered by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV2) infection MESHD, which is associated with high mortality of coronavirus disease MESHD 2019 (COVID-19). Striking similarities has been noted between COVID-19 and anti- melanoma MESHD melanoma HP differentiation-associated gene 5 (MDA5) antibody SERO (Ab)-related dermatomyositis MESHD (DM), implying a shared autoinflammatory aberrance. However, it is unclear whether anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients. Here, we found that the positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% and the anti-MDA5 Ab positive patients tended to develop severe disease MESHD (88.6% vs 66.9%, P<0.0001). In particular, the titer of anti-MDA5 Ab was increased in the non-survivals (5.95{+/-}5.16 vs 8.22{+/-}6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab ([≥]10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Overall, our data reveal that anti-MDA5 Ab is prevalent in the COVID-19 patients and high titer of this antibody SERO is correlated with severe disease MESHD and unfavorable outcomes.

    Engineered ACE2 receptor traps potently neutralize SARS-CoV-2

    Authors: Anum Glasgow; Jeff Edward Glasgow; Daniel Limonta; Paige Solomon; Irene Lui; Yang Zhang; Matthew A Nix; Nicholas J Rettko; Shion A Lim; Shoshana Zha; Rachel Yamin; Kevin Kao; Oren S Rosenberg; Jeffrey V Ravetch; Arun P Wiita; Kevin K Leung; Xin X Zhou; Tom C Hobman; Tanja K Kortemme; James A. Wells

    doi:10.1101/2020.07.31.231746 Date: 2020-08-01 Source: bioRxiv

    An essential mechanism for SARS-CoV-1 and -2 infection MESHD begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). Here we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection MESHD of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human Fc domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2 pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50) in the tens of ng/ml range. Engineered ACE2 receptor traps offer a promising route to fighting infections MESHD by SARS-CoV-2 and other ACE2-utilizing coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be pre- designed for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies SERO isolated or generated from convalescent patients.

    High effectiveness of multimodal infection MESHD control interventions in preventing SARS-CoV-2 infections MESHD in healthcare professionals: a prospective longitudinal seroconversion study

    Authors: Thomas Theo Brehm; Dorothee Schwinge; Sibylle Lampalzer; Veronika Schlicker; Julia Kuechen; Michelle Thompson; Felix Ullrich; Samuel Huber; Stefan Schmiedel; Marylyn M Addo; Marc Luetgehetmann; Johannes K Knobloch; Julian Schulze zur Wiesch; Ansgar W Lohse

    doi:10.1101/2020.07.31.20165936 Date: 2020-07-31 Source: medRxiv

    Objective: To assess the effectiveness of multimodal infection MESHD control interventions in the prevention of SARS-CoV-2 infections MESHD in healthcare professionals Design: Sequential follow-up study Setting: Largest tertiary care centre in northern Germany Participants: 1253 employees of the University Medical Center Hamburg-Eppendorf were sequentially assessed for the presence of SARS-CoV-2 IgG antibodies SERO at the beginning of the covid-19 epidemic (20 March - 9 April), one month (20 April - 8 May), and another two months later (22 June - 24 July). Of those, 1026 were healthcare workers (HCWs) of whom 292 were directly involved in the care of covid-19 patients. During the study period, infection MESHD control interventions were deployed, those included i) strict barrier nursing of all known covid-19 patients including FFP2 (N95) masks, goggles, gloves, hoods and protective gowns, ii) visitor restrictions with access control at all hospital entries, iii) mandatory wearing of disposable face masks in all clinical settings, and iv) universal RT-PCR admission screening of patients. Main Outcome Measures: SARS-CoV-2 IgG seroconversion rate Results: At the initial screening, ten participants displayed significant IgG antibody SERO ratios. Another ten individuals showed seroconversion at the second time point one month later, only two further participants seroconverted during the subsequent two months. The overall SARS-CoV-2 seroprevalence SERO in the study cohort at the last follow-up was 1.8%, the seroconversion rate dropped from 0.81% to 0.08% per month despite a longer observation period. Amongst HCWs seropositivity was increased in those directly involved in the care of patients with SARS-CoV-2 infections MESHD (3.8%, n=11) compared to other HCWs (1.4%, n=10, P=0.025). However, after the adoption of all multimodal infection MESHD control interventions seroconversions were observed in only two more HCWs, neither of whom were involved in inpatient care. Conclusion: Multimodal infection MESHD control and prevention interventions are highly effective in mitigating SARS-CoV-2 infections MESHD of healthcare professionals.

    A Newcastle disease MESHD virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

    Authors: Weina Sun; Stephen McCroskery; Wen-Chun Liu; Sarah R. Leist; Yonghong Liu; Randy A. Albrecht; Stefan Slamanig; Justine Oliva; Fatima Amanat; Alexandra Schaefer; Kenneth H. Dinnon III; Bruce L. Innis; Adolfo Garcia-Sastre; Florian Krammer; Ralph S. Baric; Peter Palese

    doi:10.1101/2020.07.30.229120 Date: 2020-07-31 Source: bioRxiv

    A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease MESHD virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies SERO in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections MESHD or significantly attenuated SARS-CoV-2 induced disease MESHD. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.

    Dynamics of epidemic diseases MESHD without guaranteed immunity

    Authors: Kurt Langfeld

    id:2007.15971v1 Date: 2020-07-31 Source: arXiv

    The global SARS-CoV-2 pandemic suggests a novel type of disease MESHD disease spread TRANS spread dynamics. WHO states that there is currently no evidence that people who have recovered from COVID-19 and have antibodies SERO are immune from a second infection MESHD [WHO]. Conventional mathematical models consider cases for which a recovered individual either becomes susceptible again or develops an immunity. Here, we study the case where infected agents recover and only develop immunity if they are continuously infected for some time. Otherwise, they become susceptible again. We show that field theory bounds the peak of the infectious rate. Consequently, the theory's phases characterise the disease MESHD dynamics: (i) a pandemic phase and (ii) a response regime. The model excellently describes the epidemic spread of the SARS-CoV-2 outbreak in the city of Wuhan, China. We find that only 30% of the recovered agents have developed an immunity. We anticipate our paper to influence the decision making upon balancing the economic impact and the pandemic impact on society. As long as disease MESHD controlling measures keep the disease MESHD dynamics in the "response regime", a pandemic escalation ('second wave') is ruled out.

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MeSH Disease
Human Phenotype

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