Corpus overview


Overview

MeSH Disease

Human Phenotype

Pneumonia (24)

Fever (11)

Hypertension (10)

Cough (6)

Lymphopenia (4)


Transmission

Seroprevalence
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    SARS-CoV-2 seroprevalence SERO survey among 18,000 healthcare and administrative personnel at hospitals, pre-hospital services, and specialist practitioners in the Central Denmark Region

    Authors: Sanne Jespersen; Susan Mikkelsen; Thomas Greve; Kathrine Agergaard Kaspersen; Martin Tolstrup; Jens Kjaergaard Boldsen; Jacob Dvinge Redder; Kent Nielsen; Anders Moensted Abildgaard; Henrik Albert Kolstad; Lars Oestergaard; Marianne Kragh Thomsen; Holger Jon Moeller; Christian Erikstrup

    doi:10.1101/2020.08.10.20171850 Date: 2020-08-12 Source: medRxiv

    Objectives: The objective of this study was to perform a large seroprevalence SERO survey on severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) among Danish healthcare workers to identify high risk groups. Design: Cross-sectional survey. Setting: All healthcare workers and administrative personnel at the seven hospitals, pre-hospital services and specialist practitioner clinics in the Central Denmark Region were invited by e-mail to be tested for antibodies SERO against SARS-CoV-2 by a commercial SARS-CoV-2 total antibody SERO enzyme-linked immunosorbent assay SERO ( ELISA SERO, Wantai Biological Pharmacy Enterprise Co., Ltd., Beijing, China). Participants: A total of 25,950 participants were invited. Of these, 17,987 (69%) showed up for blood SERO sampling, and 17,971 had samples available for SARS-CoV-2 antibody SERO testing. Main outcome measures: 1) Prevalence SERO of SARS-CoV-2 antibodies SERO; 2) Risk factors for seropositivity; 3) Association of SARS-CoV-2 RNA and antibodies SERO. Results: After adjustment for assay sensitivity SERO and specificity, the overall seroprevalence SERO was 3.4% (CI: 2.5%-3.8%). The seroprevalence SERO was higher in the western part of the region than in the eastern part (11.9% vs 1.2%, difference: 10.7 percentage points, CI: 9.5-12.2). In the high prevalence SERO area, the emergency MESHD departments had the highest seroprevalence SERO (29.7%) while departments without patients or with limited patient contact had the lowest seroprevalence SERO (2.2%). Multivariable logistic regression analysis with age TRANS, sex, and profession as the predictors showed that nursing staff, medical doctors, and biomedical laboratory scientists had a higher risk than medical secretaries, who served as reference (OR = 7.3, CI: 3.5-14.9; OR = 4., CI: 1.8-8.9; and OR = 5.0, CI: 2.1-11.6, respectively). Among the total 668 seropositive participants, 433 (64.8%) had previously been tested for SARS-CoV-2 RNA, and 50.0% had a positive RT-PCR result. A total of 98% of individuals who had a previous positive viral RNA test were also found to be seropositive. Conclusions: We found large differences in the prevalence SERO of SARS-CoV-2 antibodies SERO in staff working in the healthcare sector within a small geographical area of Denmark and signs of in-hospital transmission TRANS. Half of all seropositive staff had been tested positive by PCR prior to this survey. This study raises awareness of precautions which should be taken to avoid in-hospital transmission TRANS. Additionally, regular testing of healthcare workers for SARS-CoV-2 should be considered to identify areas with increased transmission TRANS. Trial registration: The study is approved by the Danish Data Protection Agency (1-16-02-207-20).

    A Large-Scale Clinical Validation Study Using nCapp Cloud Plus Terminal by Frontline Doctors for the Rapid Diagnosis of COVID-19 and COVID-19 pneumonia MESHD pneumonia HP in China

    Authors: Dawei Yang; Tao Xu; Xun Wang; Deng Chen; Ziqiang Zhang; Lichuan Zhang; Jie Liu; Kui Xiao; Li Bai; Yong Zhang; Lin Zhao; Lin Tong; Chaomin Wu; Yaoli Wang; Chunling Dong; Maosong Ye; Yu Xu; Zhenju Song; Hong Chen; Jing Li; Jiwei Wang; Fei Tan; Hai Yu; Jian Zhou; Jinming Yu; Chunhua Du; Hongqing Zhao; Yu Shang; Linian Huang; Jianping Zhao; Yang Jin; Charles A. Powell; Yuanlin Song; Chunxue Bai

    doi:10.1101/2020.08.07.20163402 Date: 2020-08-11 Source: medRxiv

    Background The outbreak of coronavirus disease MESHD 2019 (COVID-19) has become a global pandemic acute infectious disease MESHD, especially with the features of possible asymptomatic TRANS carriers TRANS and high contagiousness. It causes acute respiratory distress HP syndrome MESHD and results in a high mortality rate if pneumonia MESHD pneumonia HP is involved. Currently, it is difficult to quickly identify asymptomatic TRANS cases or COVID-19 patients with pneumonia MESHD pneumonia HP due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans, which facilitates the spread of the disease TRANS disease MESHD at the community level, and contributes to the overwhelming of medical resources in intensive care units. Goal This study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist global frontline doctors to efficiently and precisely diagnose asymptomatic TRANS COVID-19 patients and cases who had a false-negative RT-PCR test result. Methods With online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan Unversity (approval number B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. These patients had SARS-CoV-2 RT-PCR test results and chest CT scans, both of which were used as the gold standard for the diagnosis of COVID-19 and COVID-19 pneumonia MESHD pneumonia HP. In particular, the dataset included 137 indeterminate cases who initially did not have RT-PCR tests and subsequently had positive RT-PCR results, 62 suspected cases who initially had false-negative RT-PCR test results and subsequently had positive RT-PCR results, and 122 asymptomatic TRANS cases who had positive RT-PCR test results, amongst whom 31 cases were diagnosed. We also integrated the function of a survey in nCapp to collect user feedback from frontline doctors. Findings We applied the statistical method of a multi-factor regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are fast and accessible: 'Residing or visiting history in epidemic regions', 'Exposure history to COVID-19 patient', 'Dry cough MESHD cough HP', ' Fatigue MESHD Fatigue HP', 'Breathlessness', 'No body temperature decrease after antibiotic treatment', 'Fingertip blood SERO oxygen saturation<=93%', ' Lymphopenia MESHD Lymphopenia HP', and 'C-reactive protein (CRP) increased'. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). To ensure the sensitivity SERO of the model, we used a cutoff value of 0.09. The sensitivity SERO and specificity of the model were 98.0% (95% CI: 96.9%, 99.1%) and 17.3% (95% CI: 15.0%, 19.6%), respectively, in the training dataset, and 96.5% (95% CI: 95.1%, 98.0%) and 18.8% (95% CI: 16.4%, 21.2%), respectively, in the validation dataset. In the subset of the 137 indeterminate cases who initially did not have RT-PCR tests and subsequently had positive RT-PCR results, the model predicted 132 cases, accounting for 96.4% (95% CI: 91.7%, 98.8%) of the cases. In the subset of the 62 suspected cases who initially had false-negative RT-PCR test results and subsequently had positive RT-PCR results, the model predicted 59 cases, accounting for 95.2% (95% CI: 86.5%, 99.0%) of the cases. Considering the specificity of the model, we used a cutoff value of 0.32. The sensitivity SERO and specificity of the model were 83.5% (95% CI: 80.5%, 86.4%) and 83.2% (95% CI: 80.9%, 85.5%), respectively, in the training dataset, and 79.6% (95% CI: 76.4%, 82.8%) and 81.3% (95% CI: 78.9%, 83.7%), respectively, in the validation dataset, which is very close to the published AI model. The results of the online survey 'Questionnaire Star' showed that 90.9% of nCapp users in WeChat mini programs were 'satisfied' or 'very satisfied' with the tool. The WeChat mini program received a significantly higher satisfaction rate than other platforms, especially for 'availability and sharing convenience of the App' and 'fast speed of log-in and data entry'. Discussion With the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic TRANS patients and avoid misdiagnoses of cases with false-negative RT-PCR results. These patients require timely isolation or close medical supervision. By applying the model, medical resources can be allocated more reasonably, and missed diagnoses can be reduced. In addition, further education and interaction among medical professionals can improve the diagnostic efficiency for COVID-19, thus avoiding the transmission TRANS of the disease from asymptomatic MESHD asymptomatic TRANS patients at the community level.

    Specificity and Performance SERO of Nucleocapsid and Spike-based SARS-CoV-2 Serologic Assays

    Authors: Zahra Rikhtegaran Tehrani; Saman Saadat; Ebtehal Saleh; Xin Ouyang; Niel Constantine; Anthony L. DeVico; Anthony D. Harris; George K. Lewis; Shyam Kottilil; Mohammad M. Sajadi

    doi:10.1101/2020.08.05.20168476 Date: 2020-08-07 Source: medRxiv

    There is an urgent need for an accurate antibody test SERO for severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). In this paper, we have developed 3 ELISA SERO methods, trimer spike IgA, trimer spike IgG, and nucleocapsid IgG, for detecting anti- SARS-CoV-2 antibodies SERO. We evaluated their performance SERO in comparison with four commercial ELISAs SERO, EDI Novel Coronavirus COVID-19 ELISA IgG SERO and IgM, Euroimmun Anti-SARS-CoV-2 ELISA IgG SERO and IgA, and one lateral flow assay, DPP COVID-19 IgM/IgG System (Chembio). Both sensitivity SERO and specificity were evaluated and the causes of false-positive reactions were determined. The assays were compared using 300 pre-epidemic samples and 100 PCR-confirmed COVID-19 samples. The sensitivities SERO and specificities of the assays were as follows: 90%/100% (in-house trimer spike IgA), 90%/99.3% (in-house trimer spike IgG), 89%/98.3% (in-house nucleocapsid IgG), 73.7%/100% (EDI nucleocapsid IgM), 84.5%/95.1% (EDI nucleocapsid IgG), 95%/93.7% (Euroimmun S1 IgA), 82.8%/99.7% (Euroimmun S1 IgG), 82.0%/91.7% (Chembio nucleocapsid IgM), 92%/93.3% (Chembio nucleocapsid IgG). The presumed causes of positive signals from pre-epidemic samples in commercial and in-house assays were mixed. In some cases, positivity varied with assay repetition. In other cases, reactivity was abrogated by competitive inhibition (spiking the sample with analyte prior to performing the assay). In other cases, reactivity was consistently detected but not abrogated by analyte spiking. Overall, there was wide variability in assay performance SERO using our samples, with in-house tests exhibiting the highest combined sensitivity SERO and specificity. The causes of false positivity in pre-epidemic samples may be due to plasma SERO antibodies SERO apparently reacting with the analyte, or spurious reactivity may be directed against non-specific components in the assay system. Identification of these targets will be essential to improving assay performance SERO.

    Performance SERO of an automated anti-SARS-CoV-2 immunoassay SERO in prepandemic cohorts

    Authors: Elena Riester; Beda Krieter; Peter Findeisen; Michael Laimighofer; Kathrin Schoenfeld; Tina Laengin; Christoph Niederhauser

    doi:10.1101/2020.08.07.20169987 Date: 2020-08-07 Source: medRxiv

    Background: The Elecsys(R) Anti-SARS-CoV-2 immunoassay SERO (Roche Diagnostics) was developed to provide an accurate and reliable method for the detection of antibodies SERO to severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). We evaluated the specificity of the Elecsys Anti-SARS-CoV-2 immunoassay SERO in prepandemic sample cohorts across five sites in Germany, Austria and Switzerland. Methods: Specificity of the immunoassay SERO was evaluated using anonymised, frozen, residual serum SERO and/or plasma SERO samples from blood SERO donors or routine diagnostic testing. All samples were collected before September 2019 and therefore presumed negative for SARS-CoV-2-specific antibodies SERO. Cohorts included samples from blood SERO donors, pregnant women and paediatric patients. Point estimates and 95% confidence intervals (CIs) were calculated. Results: Overall specificities for the Elecsys Anti-SARS-CoV-2 immunoassay SERO in 9575 samples from blood SERO donors (n = 6714) and diagnostic specimens (n = 2861) were 99.82% (95% CI 99.69-99.91) and 99.93% (95% CI 99.75-99.99), respectively. Among 2256 samples from pregnant women, specificity was 99.91% (95% CI 99.68-99.99). Among 205 paediatric samples, specificity was 100% (95% CI 98.22-100). Conclusion: The Elecsys Anti-SARS-CoV-2 immunoassay SERO demonstrated a very high specificity across blood SERO donor samples and diagnostic specimens from Germany, Austria and Switzerland. Our findings support the use of the Elecsys Anti-SARS-CoV-2 immunoassay SERO as a potential tool for determination of an immune response following previous exposure to SARS-CoV-2 in the general population, including in blood SERO donors, pregnant women and paediatric populations.

    Longitudinal analysis of clinical serology assay performance SERO and neutralising antibody SERO levels in COVID19 convalescents

    Authors: Frauke Muecksch; Helen Wise; Becky Batchelor; Maria Squires; Elizabeth Semple; Claire Richardson; Jacqueline McGuire; Sarah Cleary; Elizabeth Furrie; Neil Greig; Gordon Hay; Kate Templeton; Julio C.C. Lorenzi; Theodora Hatziioannou; Sara J Jenks; Paul Bieniasz

    doi:10.1101/2020.08.05.20169128 Date: 2020-08-06 Source: medRxiv

    Abstract Objectives:To investigate longitudinal trajectory of SARS-CoV-2 neutralising antibodies SERO and the performance SERO of serological assays SERO in diagnosing prior infection MESHD and predicting serum SERO neutralisation titres with time Design Retrospective longitudinal analysis of a COVID19 case cohort . Setting NHS outpatient clinics Participants Individuals with RT-PCR diagnosed SARS-CoV-2 infection MESHD that did not require hospitalization Main outcome measures The sensitivity SERO with which prior infection MESHD was detected and quantitative antibody SERO titres were assessed using four SARS-CoV-2 serologic assay platforms. Two platforms employed SARS-CoV-2 spike (S) based antigens and two employed nucleocapsid (N) based antigens. Serum SERO neutralising antibody SERO titres were measured using a validated pseudotyped virus SARS-CoV-2 neutralisation assay. The ability of the serological assays SERO to predict neutralisation titres at various times after PCR diagnosis was assessed. Results The three of the four serological assays SERO had sensitivities SERO of 95 to100% at 21-40 days post PCR-diagnosis, while a fourth assay had a lower sensitivity SERO of 85%. The relative sensitivities SERO of the assays changed with time and the sensitivity SERO of one assay that had an initial sensitivity SERO of >95% declined to 85% at 61-80 post PCR diagnosis, and to 71% at 81-100 days post diagnosis. Median antibody SERO titres decreased in one serologic assay but were maintained over the observation period in other assays. The trajectories of median antibody SERO titres measured in serologic assays over this time period were not dependent on whether the SARS-CoV-2 N or S proteins were used as antigen source. A broad range of SARS-CoV-2 neutralising titres were evident in individual sera, that decreased over time in the majority of participants; the median neutralisation titre in the cohort decreased by 45% over 4 weeks. Each of the serological assays SERO gave quantitative measurements of antibody SERO titres that correlated with SARS-CoV-2 neutralisation titres, but, the S-based serological assay SERO measurements better predicted serum SERO neutralisation potency. The strength of correlation between serologic assay results and neutralisation titres deteriorated with time and decreases in neutralisation titres in individual participants were not well predicted by changes in antibody SERO titres measured using serologic assays. Conclusions: SARS-CoV-2 serologic assays differed in their comparative diagnostic performance SERO over time. Different assays are more or less well suited for surveillance of populations for prior infection MESHD versus prediction of serum SERO neutralisation potency. Continued monitoring of declining neutralisation titres during extended follow up should facilitate the establishment of appropriate serologic correlates of protection against SARS-CoV-2 reinfection.

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

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

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

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

    Analytical and clinical performances SERO of five immunoassays SERO for the detection of SARS-CoV-2 antibodies SERO in comparison with neutralization activity

    Authors: Mario Plebani; Andrea Padoan; Laura Sciacovelli; Francesco Bonfante; Matteo Pagliari; Dania Bozzato; Chiara Cosma; Alessio Bortolami; Davide Negrini; Silvia Zuin

    doi:10.1101/2020.08.01.20166546 Date: 2020-08-04 Source: medRxiv

    Background. Reliable high-throughput serological assays SERO for SARS-CoV-2 antibodies SERO (Abs) are urgently needed for the effective containment of the COVID-19 pandemic, as it is of crucial importance to understand the strength and duration of immunity after infection MESHD, and to make informed decisions concerning the activation or discontinuation of physical distancing restrictions. Methods. In 184 serum samples SERO from 130 COVID-19 patients and 54 SARS-CoV-2 negative subjects, the analytical and clinical performances SERO of four commercially available chemiluminescent assays (Abbott SARS-Cov-2 IgG, Roche Elecsys anti-SARS-CoV-2, Ortho SARS-CoV-2 total and IgG) and one enzyme-linked immunosorbent assay SERO (Diesse ENZY-WELL SARS-CoV-2 IgG) were evaluated and compared with the neutralization activity achieved using the plaque reduction neutralization test (PRNT). Findings. Precision results ranged from 0.9% to 11.8% for all assays. Elecsys anti-SARS-CoV-2 demonstrated linearity of results at concentrations within the cut-off value. Overall, sensitivity SERO ranged from 78.5 to 87.8%, and specificity, from 97.6 to 100%. On limiting the analysis to samples collected 12 days after onset of symptoms TRANS, the sensitivity SERO of all assays increased, the highest value (95.2%) being obtained with VITRO Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG. The strongest PRNT50 correlation with antibody SERO levels was obtained with ENZY-Well SARS-CoV-2 IgG (rho = 0.541, p < 0.001). Interpretation. The results confirmed that all immunoassays SERO had an excellent specificity, whereas sensitivity SERO varied across immunoassays SERO, depending strongly on the time interval between symptoms onset TRANS and sample collection. Further studies should be conducted to achieve a stronger correlation between antibody SERO measurement and PRNT50 in order to obtain useful information for providing effective passive antibody SERO therapy, and developing a vaccine against the SARS-CoV-2 virus.

    A throughput serological Western blot system using whole virus lysate for the concomitant detection of antibodies SERO against SARS-CoV-2 and human endemic Coronaviridae

    Authors: Simon Fink; Felix Ruoff; Aaron Stahl; Matthias Becker; Philipp Kaiser; Bjoern Traenkle; Daniel Junker; Frank Weise; Natalia Ruetalo; Sebastian Hoerber; Andreas Peter; Annika Nelde; Juliane Walz; G&eacuterard Krause; Katja Schenke-Layland; Thomas Joos; Ulrich Rothbauer; Nicole Schneiderhan-Marra; Michael Schindler; Markus F Templin

    doi:10.1101/2020.07.31.20165019 Date: 2020-08-04 Source: medRxiv

    BACKGROUND: Seroreactivity against human endemic coronaviruses has been linked to disease MESHD severity after SARS-CoV-2 infection MESHD. Assays that are capable of concomitantly detecting antibodies SERO against endemic coronaviridae such as OC43, 229E, NL63, and SARS-CoV-2 may help to elucidate this question. We set up a platform for serum SERO-screening and developed a bead-based Western blot system, namely DigiWest, capable of running hundreds of assays using microgram amounts of protein prepared directly from different viruses. METHODS: The parallelized and miniaturised DigiWest assay was adapted for detecting antibodies SERO using whole protein extract prepared from isolated SARS-CoV-2 virus particles. After characterisation and optimization of the newly established test, whole virus lysates of OC43, 229E, and NL63 were integrated into the system. RESULTS: The DigiWest-based immunoassay SERO system for detection of SARS-CoV-2 specific antibodies SERO shows a sensitivity SERO of 87.2 % and diagnostic specificity of 100 %. Concordance analysis with the SARS-CoV-2 immunoassays SERO available by Roche, Siemens, and Euroimmun indicates a comparable assay performance SERO (Cohen's Kappa ranging from 0.8799-0.9429). In the multiplexed assay, antibodies SERO against the endemic coronaviruses OC43, 229E, and NL63 were detected, displaying a high incidence of seroreactivity against these coronaviruses. CONCLUSION: The DigiWest-based immunoassay SERO, which uses authentic antigens from isolated virus particles, is capable of detecting individual serum SERO responses against SARS-CoV-2 with high specificity and sensitivity SERO in one multiplexed assay. It shows high concordance with other commercially available serologic assays. The DigiWest approach enables a concomitant detection of antibodies SERO against different endemic coronaviruses and will help to elucidate the role of these possibly cross-reactive antibodies SERO.

    SARS-CoV-2 antigens expressed in plants detect antibody SERO responses in COVID-19 patients

    Authors: Mohau S Makatsa; Marius B Tincho; Jerome M Wendoh; Sherazaan D Ismail; Rofhiwa Nesamari; Francisco Pera; Scott de Beer; Anura David; Sarika Jugwanth; Maemu P Gededzha; Nakampe Mampeule; Ian Sanne; Wendy Stevens; Lesley Scott; Jonathan Blackburn; Elizabeth S Mayne; Roanne S Keeton; Wendy A Burgers

    doi:10.1101/2020.08.04.20167940 Date: 2020-08-04 Source: medRxiv

    Background: The SARS-CoV-2 pandemic has swept the world and poses a significant global threat to lives and livelihoods, with over 16 million confirmed cases TRANS and at least 650 000 deaths MESHD from COVID-19 in the first 7 months of the pandemic. Developing tools to measure seroprevalence SERO and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay SERO using plant-derived recombinant viral proteins, which represent important tools in less-resourced settings. Methods: We established an indirect enzyme-linked immunosorbent assay SERO ( ELISA SERO) using the S1 and receptor-binding domain (RBD) portions of the spike protein from SARS-CoV-2, expressed in Nicotiana benthamiana. We measured antibody SERO responses in sera from South African patients (n=77) who had tested positive by PCR for SARS-CoV-2. Samples were taken a median of six weeks after the diagnosis, and the majority of participants had mild and moderate COVID-19 disease MESHD. In addition, we tested the reactivity of pre-pandemic plasma SERO (n=58) and compared the performance SERO of our in-house ELISA SERO with a commercial assay. We also determined whether our assay could detect SARS-CoV-2-specific IgG and IgA in saliva. Results: We demonstrate that SARS-CoV-2-specific immunoglobulins are readily detectable using recombinant plant-derived viral proteins, in patients who tested positive for SARS-CoV-2 by PCR. Reactivity to S1 and RBD was detected in 51 (66%) and 48 (62%) of participants, respectively. Notably, we detected 100% of samples identified as having S1-specific antibodies SERO by a validated, high sensitivity SERO commercial ELISA SERO, and OD values were strongly and significantly correlated between the two assays. For the pre-pandemic plasma SERO, 1/58 (1.7%) of samples were positive, indicating a high specificity for SARS-CoV-2 in our ELISA SERO. SARS-CoV-2-specific IgG correlated significantly with IgA and IgM responses. Endpoint titers of S1- and RBD-specific immunoglobulins ranged from 1:50 to 1:3200. S1-specific IgG and IgA were found in saliva samples from convalescent volunteers. Conclusions: We demonstrate that recombinant SARS-CoV-2 proteins produced in plants enable robust detection of SARS-CoV-2 humoral responses. This assay can be used for seroepidemiological studies and to measure the strength and durability of antibody SERO responses to SARS-CoV-2 in infected patients in our setting.

    Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection MESHD at Both Individual and Population Levels

    Authors: Thomas M Snyder; Rachel M Gittelman; Mark Klinger; Damon H May; Edward J Osborne; Ruth Taniguchi; H Jabran Zahid; Ian M Kaplan; Jennifer N Dines; Matthew N Noakes; Ravi Pandya; Xiaoyu Chen; Summer Elasady; Emily Svejnoha; Peter Ebert; Mitchell W Pesesky; Patricia De Almeida; Hope O'Donnell; Quinn DeGottardi; Gladys Keitany; Jennifer Lu; Allen Vong; Rebecca Elyanow; Paul Fields; Julia Greissl; Lance Baldo; Simona Semprini; Claudio Cerchione; Massimiliano Mazza; Ottavia M Delmonte; Kerry Dobbs; Gonzalo CarreƱo-Tarragona; Santiago Barrio; Luisa Imberti; Alessandra Sottini; Eugenia Quiros-Roldan; Camillo Rossi; Andrea Biondi; Laura Rachele Bettini; Mariella D'Angio; Paolo Bonfanti; Miranda F Tompkins; Camille Alba; Clifton Dalgard; Vittorio Sambri; Giovanni Martinelli; Jason D Goldman; James R Heath; Helen C Su; Luigi D Notarangelo; Joaquin Martinez-Lopez; Jonathan M Carlson; Harlan S Robins

    doi:10.1101/2020.07.31.20165647 Date: 2020-08-04 Source: medRxiv

    T cells are involved in the early identification and clearance of viral infections MESHD and also support the development of antibodies SERO by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection MESHD. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides (class II data in a forthcoming study). Then, at the population level, we performed T-cell repertoire sequencing on 1,015 samples (from 827 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection MESHD from both CD8 and CD4 T cells. Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection MESHD and is detectable for several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection MESHD based solely on TCR sequencing from blood SERO samples, and observed, at 99.8% specificity, high early sensitivity SERO soon after diagnosis (Day 3-7 = 83.8% [95% CI = 77.6-89.4]; Day 8-14 = 92.4% [87.6-96.6]) as well as lasting sensitivity SERO after recovery (Day 29+/convalescent = 96.7% [93.0-99.2]). These results demonstrate an approach to reliably assess the adaptive immune response both soon after viral antigenic exposure (before antibodies SERO are typically detectable) as well as at later time points. This blood SERO-based molecular approach to characterizing the cellular immune response has applications in vaccine development as well as clinical diagnostics and monitoring.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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