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MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Serial SARS-CoV-2 Seropravelence Studies in Delhi July-August 2020: Indications of Pre-existing Cross-reactive Antibodies SERO and Implications for Disease Progression

    Authors: Smarajit Dey

    doi:10.21203/rs.3.rs-80259/v1 Date: 2020-09-18 Source: ResearchSquare

    Two seropravelence studies were undertaken in Delhi, the city-state capital of India, in July-August 2020, exactly one month apart, to test for SARS-CoV-2 antibodies SERO. Virus-tested (mostly RT-PCR) caseloads corresponding to these surveys, as of 13 days earlier to ensure antibody SERO generation, were compared. The survey conducted June 26-July 10 (sample size 21387) showed 23.48% seropravelence, (extrapolated to 4.48 mn of Delhi population of 19.1 mn), which was 79-times higher than corresponding virus-tested positives totaling 56746. Survey conducted August 1-7 (15311 samples) showed 29.1% antibody SERO-positive (5.56 mn population), and was 44x of virus-tested positive total of 125096. Pointing out that all serological surveys world-over have shown antibody SERO-positives to be higher than virus-test positives by multiples 7x to 80x, this study seeks to examine why the multiple should decline so drastically in one month, from 79x to 44x. Statistical adjustments were performed for Sampling Error and Sensitivity SERO/Specificity of the diagnostic kits. Indigenously developed COVID KAVACH ELISA SERO tests for IgG antibodies SERO to the SARS-CoV-2 virus were used for the surveys. Significantly, statistical adjustments were also done to account for the Testing Volumes and (Spot) Positivity rates at the two different times. [Spot Positivity is defined in the study and is the closest estimate of current or fresh positivity.] After all statistical revisions, the antibody SERO-positive to virus-test positive multiples stood at 53x and 37x for the two surveys. Calculating across the two sets of data, and other sensitivity SERO analysis, the study indicates that there is a significant proportion of pre-existing cross-reactive antibodies SERO (possibly to the HCoV viruses), that are seropositive in SARS-CoV-2 antibody SERO tests, to the extent of 16%-19% of the population. The study also infers that there is an Amplification Factor of 15 in the Delhi serostudies: ie, each virus-test positive represents 14 more who are possibly asymptomatic TRANS and untested. The study forecasts a seropravelence 31%-34% for the 3rd serial serosurvey scheduled in September, whose results expected 22nd September. Limitations of the study are discussed, notably the absence of any research paper on the survey techniques, antibody testing SERO controversies, and the statistical adjustment for Testing Volumes. The study discusses how Chain-of-Transmission TRANS protocols and Decreasing Susceptible Population work in unison to slow down a pandemic, and analyses the disease progression graph of Delhi in that context. The implications of 16%-19% pre-existing antibodies SERO on disease progression in Delhi are discussed. 

    A dual antigen ELISA SERO allows the assessment of SARS-CoV-2 antibody SERO seroprevalence SERO in a low transmission TRANS setting

    Authors: Sarah Hicks; Kai Pohl; Teresa Neeman; Hayley McNamara; Kate Parsons; Jin-Shu He; Sidra Ali; Samina Nazir; Louise Rowntree; Thi Nguyen; Katherine Kedzierska; Denise Doolan; Carola Vinuesa; Matthew Cook; Nicholas Coatsworth; Paul Myles; Florian Kurth; Leif Sander; Russell Gruen; Graham Mann; Amee George; Elizabeth Gardiner; Ian Cockburn; Bala Pesala; Debojyoti Chakraborty; Souvik Maiti

    doi:10.1101/2020.09.09.20191031 Date: 2020-09-14 Source: medRxiv

    Estimates of seroprevalence SERO of SARS-CoV-2 antibodies SERO have been hampered by inadequate assay sensitivity SERO and specificity. Using an ELISA SERO-based approach to that combines data about IgG responses to both the Nucleocapsid and Spike-receptor binding domain antigens, we show that near-optimal sensitivity SERO and specificity can be achieved. We used this assay to assess the frequency of virus-specific antibodies SERO in a cohort of elective surgery patients in Australia and estimated seroprevalence SERO in Australia to be 0.28% (0 to 0.72%). These data confirm the low level of transmission TRANS of SARS-CoV-2 in Australia before July 2020 and validate the specificity of our assay.

    Insights into the practical effectiveness of RT-PCR testing for SARS-CoV-2 from serologic data, a cohort study

    Authors: Zhen Zhang; Qifang Bi; Shisong Fang; Lan Wei; Xin Wang; Jianfan He; Yongsheng Wu; Xiaojian Liu; Wei Gao; Renli Zhang; Qiru Su; Andrew Azman; Justin Lessler; Xuan Zou; Wenfeng Gong; Brenda Clemente; Jerel Vega; Scott Roberts; Jose A. Gonzalez; Marciano Sablad; Rodrigo Yelin; Wendy Taylor; Kiyoshi Tachikawa; Suezanne Parker; Priya Karmali; Jared Davis; Sean M Sullivan; Steve G. Hughes; Pad Chivukula; Eng Eong Ooi

    doi:10.1101/2020.09.01.20182469 Date: 2020-09-03 Source: medRxiv

    Background: Virologic detection of SARS-CoV-2 through Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) has limitations for surveillance. Serologic tests SERO can be an important complementary approach. Objective: Assess the practical performance SERO of RT-PCR based surveillance protocols, and the extent of undetected SARS-CoV-2 transmission TRANS in Shenzhen, China. Design: Cohort study nested in a public health response. Setting: Shenzhen, China; January-May 2020. Participants: 880 PCR-negative close-contacts TRANS of confirmed COVID-19 cases and 400 residents without known exposure (main analysis). Fifty-seven PCR-positive case contacts (timing analysis). Measurements: Virological testing by RT-PCR. Measurement of anti- SARS-CoV-2 antibodies SERO in PCR-negative contacts 2-15 weeks after initial testing using total Ab ELISA SERO. Rates of undetected infection MESHD, performance SERO of RT-PCR over the course of infection MESHD, and characteristics of seropositive but PCR-negative individuals were assessed. Results: The adjusted seropositivity rate for total Ab among 880 PCR-negative close-contacts TRANS was 4.1% (95%CI, 2.9% to 5.7%), significantly higher than among residents without known exposure to cases (0.0%, 95%CI, 0.0% to 1.0%). PCR-positive cases were 8.0 times (RR; 95% CI, 5.3 to 12.7) more likely to report symptoms than the PCR-negative individuals who were seropositive, but otherwise similar. RT-PCR missed 36% (95%CI, 28% to 44%) of infected close-contacts TRANS, and false negative rates appear to be highly dependent on stage of infection MESHD. Limitations: No serological data were available on PCR-positive cases. Sample size was limited, and only 20% of PCR-negative contacts met inclusion criteria. Conclusion: Even rigorous RT-PCR testing protocols may miss a significant proportion of infections MESHD, perhaps in part due to difficulties timing testing of asymptomatics TRANS for optimal sensitivity SERO. Surveillance and control protocols relying on RT-PCR were, nevertheless, able to contain community spread in Shenzhen.

    Seroprevalence SERO and immunity of SARS-CoV-2 infection MESHD in children TRANS and adolescents in schools in Switzerland: design for a longitudinal, school-based prospective cohort study

    Authors: Agne Ulyte; Thomas Radtke; Irene Abela; Sarah H Haile; Julia Braun; Ruedi Jung; Christoph Berger; Alexandra Trkola; Jan Fehr; Milo A Puhan; Susi Kriemler; Anel Nurtay; Lucie Abeler-Dörner; David G Bonsall; Michael V McConnell; Shawn O'Banion; Christophe Fraser; Scott Roberts; Jose A. Gonzalez; Marciano Sablad; Rodrigo Yelin; Wendy Taylor; Kiyoshi Tachikawa; Suezanne Parker; Priya Karmali; Jared Davis; Sean M Sullivan; Steve G. Hughes; Pad Chivukula; Eng Eong Ooi

    doi:10.1101/2020.08.30.20184671 Date: 2020-09-02 Source: medRxiv

    Introduction Seroprevalence SERO and transmission TRANS routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD in children TRANS and adolescents, especially in school setting, are not clear. Resulting uncertainty is reflected in very different decisions on school closures and reopenings across countries. The aim of this longitudinal cohort study is to assess the extent and patterns of seroprevalence SERO of SARS-CoV-2 antibodies SERO in school-attending children TRANS repeatedly. It will examine risk factors for infection MESHD, relationship between seropositivity and symptoms, and temporal persistence of antibodies SERO. Additionally, it will include testing of school personnel and parents TRANS. Methods and analysis The study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children TRANS aged TRANS 5 to 16 years, attending classes in primary and secondary schools are invited. Venous blood MESHD blood SERO and saliva samples are collected for SARS-CoV-2 serological testing SERO after the first wave of infections (June/July 2020), in fall HP (October/November 2020), and after winter (March/April 2021). Venous blood MESHD blood SERO is also collected for serological testing SERO of parents TRANS and school personnel. Bi-monthly questionnaires to children TRANS, parents TRANS and school personnel cover SARS-CoV-2 symptoms MESHD and tests, health, preventive behavior, lifestyle and quality of life information. Total seroprevalence SERO and cumulative incidence will be calculated. Hierarchical Bayesian logistic regression models will account for sensitivity SERO and specificity of the serological test SERO in the analyses and for the complex sampling structure, i.e., clustering within classes and schools. Ethics and dissemination The study was approved by the Ethics Committee of the Canton of Zurich, Switzerland (2020-01336). The results of this study will be published in peer-reviewed journals and will be made available to study participants and participating schools, the Federal Office of Public Health, and the Educational Department of the canton of Zurich. Trial registration number NCT04448717.

    Universal PCR and antibody testing SERO demonstrate little to no transmission TRANS of SARS-CoV-2 in a rural community

    Authors: Ayesha Appa; Saki Takahashi; Isabel Rodriguez-Barraquer; Gabriel Chamie; Aenor Sawyer; - CLIAHUB Consortium; Elias Duarte; Jill Hakim; Keirstinne Turcios; Joanna Vinden; Owen Janson; Aashish Manglik; Michael J. Peluso; Steven G Deeks; Timothy J. Henrich; Leonel Torres; Mary Rodgers; John Hackett; Charles Y Chiu; Diane Havlir; Bryan Greenhouse

    doi:10.1101/2020.08.15.20175786 Date: 2020-08-17 Source: medRxiv

    Background: The absence of systematic surveillance for SARS-CoV-2 has curtailed accurate appraisal of transmission TRANS intensity. Our objective was to perform case detection of an entire rural community to quantify SARS-CoV-2 transmission TRANS using PCR and antibody testing SERO. Methods: We conducted a cross-sectional survey of the prevalence SERO and cumulative incidence of SARS-CoV-2 infection MESHD in the rural town of Bolinas, California (population 1,620), four weeks following shelter-in-place orders. Residents and county essential workers were tested between April 20th-24th, 2020. Prevalence SERO by PCR and seroprevalence SERO combining data from two forms of antibody testing SERO were performed in parallel (Abbott ARCHITECT IgG to nucleocapsid protein and in-house IgG ELISA SERO to the receptor binding domain). Results: Of 1,891 participants, 1,312 were confirmed Bolinas residents (>80% community ascertainment). Zero participants were PCR positive. Assuming 80% sensitivity SERO, it would have been unlikely to observe these results (p<0.05) if there were >3 active infections in the community. Based on antibody SERO results, estimated prevalence SERO of prior infection was 0.16% (95% CrI: 0.02%, 0.46%). Seroprevalence SERO estimates using only one of the two tests would have been higher, with greater uncertainty. The positive predictive value SERO (PPV) of a positive result on both tests was 99.11% (95% CrI: 95.75%, 99.94%), compared to PPV 44.19%-63.32% (95% CrI range 3.25%-98.64%) if only one test was utilized. Conclusions: Four weeks following shelter-in-place, active and prior SARS-CoV-2 infection MESHD in a rural Northern California community was extremely rare. In this low prevalence SERO setting, use of two antibody tests SERO increased the PPV and precision of seroprevalence SERO estimates.

    Evaluation of commercially available immuno-magnetic agglutination and enzyme-linked immunosorbent assays SERO for rapid point-of-care diagnostics of COVID-19

    Authors: Maria Engel Moeller; Jeppe Fock; Pearlyn Pah; Antia De La Campa Veras; Melanie Bade; Marco Donolato; Simone Bastrup Israelsen; Jesper Eugen-Olsen; Thomas Benfield; Frederik Neess Engsig; Justin Manalac; Ana R Otrelo-Cardoso; Tho D Pham; Arjun Rustagi; Angela J Rogers; Nigam H Shah; Catherine A Blish; Jennifer R Cochran; Kari C Nadeau; Theodore S Jardetzky; James L Zehnder; Taia T Wang; Peter S Kim; Saurabh Gombar; Robert Tibshirani; Benjamin A Pinsky; Scott D Boyd

    doi:10.1101/2020.08.15.20172080 Date: 2020-08-17 Source: medRxiv

    Introduction: Coronavirus Disease MESHD 2019 (COVID-19) is caused by severe acute respiratory coronavirus-2 (SARS-CoV-2). Fast, accurate and simple blood SERO-based assays for quantification of anti- SARS-CoV-2 antibodies SERO are urgently needed to identify infected individuals and keep track of the spread of disease TRANS. Methods: The study included 35 plasma SERO samples from 22 individuals with confirmed COVID-19 by real time reverse transcriptase polymerase chain reaction and 40 non COVID-19 plasma SERO samples. Anti-SARS-CoV-2 IgM/IgA or IgG antibodies SERO were detected by a microfluidic quantitative immunomagnetic assay (IMA)(ViroTrack Sero COVID IgM+IgA/IgG Ab, Blusense Diagnostics, Denmark) and by enzyme-linked immunosorbent assay SERO (( ELISA SERO) (EuroImmun Medizinische Labordiagnostika, Germany). Results: Of the 35 plasma SERO samples from the COVID-19 patients, 29 (82.9%) were positive for IgA/IgM or IgG by IMA and 29 samples (82.9%) were positive by ELISA SERO. Sensitivity SERO for only one sample per patient was 68% for IgA+IgM and 73% IgG by IMA and 73% by ELISA SERO. For samples collected 14 days after symptom onset TRANS, the sensitivity SERO of both IMA and ELISA SERO was around 90%. Specificity of the IMA reached 100% compared to 95% for ELISA IgA SERO and 97.5% for ELISA IgG SERO. Conclusion: IMA for COVID-19 is a rapid simple-to-use point of care test with sensitivity SERO and specificity similar to a commercial ELISA SERO.

    Antibody SERO prevalence SERO for SARS-CoV-2 in England following first peak of the pandemic: REACT2 study in 100,000 adults TRANS

    Authors: Helen Ward; Christina J Atchison; Matthew Whitaker; Kylie E. C. Ainslie; Joshua Elliott; Lucy C Okell; Rozlyn Redd; Deborah Ashby; Christl A. Donnelly; Wendy Barclay; Ara Darzi; Graham Cooke; Steven Riley; Paul Elliott; Rachel Vreeman; Joseph Masci; Nick A Maskell; Shaney Barratt

    doi:10.1101/2020.08.12.20173690 Date: 2020-08-14 Source: medRxiv

    Background England, UK has experienced a large outbreak of SARS-CoV-2 infection MESHD. As in USA and elsewhere, disadvantaged communities have been disproportionately affected. Methods National REal-time Assessment of Community Transmission TRANS-2 (REACT-2) seroprevalence SERO study using self-administered lateral flow immunoassay SERO (LFIA) test for IgG among a random population sample of 100,000 adults TRANS over 18 years in England, 20 June to 13 July 2020. Results Completed questionnaires were available for 109,076 participants, yielding 5,544 IgG positive results and adjusted (for test performance SERO), re-weighted (for sampling) prevalence SERO of 6.0% (95% CI: 5.8, 6.1). Highest prevalence SERO was in London (13.0% [12.3, 13.6]), among people of Black or Asian (mainly South Asian) ethnicity (17.3% [15.8, 19.1] and 11.9% [11.0, 12.8] respectively) and those aged TRANS 18-24 years (7.9% [7.3, 8.5]). Care home workers with client-facing roles had adjusted odds ratio of 3.1 (2.5, 3.8) compared with non-essential workers. One third (32.2%, [31.0-33.4]) of antibody SERO positive individuals reported no symptoms. Among symptomatic cases, the majority (78.8%) reported symptoms during the peak of the epidemic in England in March (31.3%) and April (47.5%) 2020. We estimate that 3.36 million (3.21, 3.51) people have been infected with SARS-CoV-2 in England to end June 2020, with an overall infection MESHD fatality ratio of 0.90% (0.86, 0.94). Conclusion The pandemic of SARS-CoV-2 infection MESHD in England disproportionately affected ethnic minority groups and health and care home workers. The higher risk of infection TRANS risk of infection TRANS infection MESHD in these groups may explain, at least in part, their increased risk of hospitalisation and mortality from COVID-19.

    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 coronavirus 2 MESHD (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 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).

    SARS-CoV-2 antibody SERO responses determine disease severity in COVID-19 infected individuals

    Authors: Cecilie Bo Hansen; Ida Jarlhelt; Laura Pérez-Alós; Lone Hummelshøj Landsy; Mette Loftager; Anne Rosbjerg; Charlotte Helgstrand; Jais Rose Bjelke; Thomas Egebjerg; Joseph G. Jardine; Charlotte Sværke Jørgensen; Kasper Iversen; Rafael Bayarri-Olmos; Peter Garred; Mikkel-Ole Skjoedt

    doi:10.1101/2020.07.27.20162321 Date: 2020-07-29 Source: medRxiv

    Globally, the COVID-19 pandemic has had extreme consequences for the healthcare system and calls for diagnostic tools to monitor and understand the transmission TRANS, pathogenesis and epidemiology, as well as to evaluate future vaccination strategies. Here we have developed novel flexible ELISA SERO-based assays for specific detection of SARS-CoV-2 antibodies SERO against the receptor-binding domain (RBD): An antigen sandwich- ELISA SERO relevant for large population screening and three isotype-specific assays for in-depth diagnostics. Their performance SERO was evaluated in a cohort of 350 convalescent participants with previous COVID-19 infection, ranging from asymptomatic TRANS to critical cases. We mapped the antibody SERO responses to different areas on protein N and S and showed that the IgM, A and G antibody SERO responses against RBD are significantly correlated to the disease severity. These assays-and the data generated from them-are highly relevant for diagnostics and prognostics and contribute to the understanding of long-term COVID-19 immunity.

    SARS-CoV-2 antibody SERO prevalence SERO in health care workers: Preliminary report of a single center study

    Authors: Michael Brant-Zawadzki; Deborah Fridman; Philip Robinson; Matthew Zahn; Randy German; Marcus Breit; Junko Hara

    doi:10.1101/2020.07.20.20158329 Date: 2020-07-25 Source: medRxiv

    SARS-CoV-2 has driven a pandemic crisis. Serological surveys have been conducted to establish prevalence SERO for covid-19 antibody SERO in various cohorts and communities. However, the prevalence SERO among healthcare workers is still being analyzed. The present study reports on initial sero-surveillance conducted on healthcare workers at a regional hospital system in Orange County, California, during May and June, 2020. Study participants were recruited from the entire hospital employee workforce and the independent medical staff. Data were collected for job title, location, covid-19 symptoms, a PCR test history, travel TRANS record since January 2020, and existence of household contacts TRANS with covid-19. A blood SERO sample was collected from each subject for serum SERO analysis for IgG antibodies SERO to SARS-CoV-2. Of 3,013 tested individuals, a total 2,932 were included in the analysis due to some missing data. Observed prevalence SERO of 1.06% (31 antibody SERO positive cases), adjusted prevalence SERO of 1.13% for test sensitivity SERO and specificity were identified. Significant group differences between positive vs. negative were observed for age TRANS (z = 2.65, p = .008), race (p = .037), presence of fever HP fever MESHD (p < .001) and loss of smell (p < .001). Possible explanation for this low prevalence SERO includes a relatively low local geographic community prevalence SERO (~4.4%) at the time of testing, the hospital's timely procurement of personal protective equipment, rigorous employee education MESHD, patient triage and treatment protocol development and implementation. In addition, possible greater presence of cross-reactive adaptive T cell mediated immunity in healthcare workers vs. the general population may have contributed. Determining antibody SERO prevalence SERO in front-line workers, and duration of antibody SERO presence may help stratify the workforce for risk, establish better health place policies and procedures, and potentially better mitigate transmission TRANS.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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