Testing for SARS-CoV-2 antibodies

Watson, Jessica; Richter, Alex; Deeks, Jonathan J

doi:10.1136/bmj.m3325

Cited by 89 publications

(86 citation statements)

References 20 publications

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“…As previously described, there is no clear gold standard for reference against which to assess SARS-CoV-2 immunoassays. A positive RT-PCR test has been used previously as a reference standard, although limited by a high rate of false negatives, failure in some cases to develop IgG antibodies (sero-silence or lack of antibody against the same antigenic component of the virus as the immunoassay uses as a capture antigen), or the lack of RT-PCR testing availability early in the pandemic 3,5,15 . Self-assessment of symptoms for COVID-19 disease is a poor indicator of previous infection, even among healthcare workers 16 .…”

Section: Discussionmentioning

confidence: 99%

“…RT-qPCR assays are labour and reagent intensive, limited by a short temporal window for positive diagnosis, and exhibit potential for false negative results 4 . Evidence suggests sensitivity of RT-qPCR can be as low as 70% 5 . Lockdown measures and “flattening the curve” strategies meant many infected individuals were instructed to self-isolate and were not offered a diagnostic RT-qPCR, with much of the testing limited to patients admitted to hospital, who perhaps reflect a more severely infected cohort.…”

Section: Introductionmentioning

confidence: 99%

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Laboratory evaluation of SARS-CoV-2 antibodies: detectable IgG up to 20 weeks post infection

Lj¹,

Js²,

Blighe³

et al. 2020

Preprint

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Background The SARS-CoV-2 pandemic necessitated rapid and global responses across all areas of healthcare, including an unprecedented interest in serological immunoassays to detect antibodies to the virus. The dynamics of the immune response to SARS-CoV-2 is still not well understood. Methods We measure SARS-CoV-2 antibody levels in plasma samples from 880 people in Northern Ireland by Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays to analyse immune dynamics over time. Using these results, we develop a "pseudo gold standard" reference cohort against which to assess immunoassay performance. We report performance metrics for the UK-RTC AbC-19 rapid lateral flow immunoassay (LFIA) against a characterised panel of 304 positives established using the "pseudo gold standard" system and 350 negative samples. Results We detect persistence of SARS-CoV-2 IgG up to 140 days (20 weeks) post infection, across all three antibody immunoassays, at levels up to 4.4 times the cut-off for a positive result by Roche measurement. Using our "pseudo gold standard" cohort (n=348 positive, n=510 negative) we determine the sensitivity and specificity of the three commercial immunoassays used (EuroImmun; Sens. 98.9% [97.7-99.7%]; Spec. 99.2% [98.4-99.8%]; Roche; Sens. 99.4% [98.6-100%]; Spec. (96.7% [95.1-98.2%]; Abbott; Sens. 86.8% [83.1-90.2%]; Spec. (99.2% [98.4-99.8%]). The UK-RTC AbC-19 lateral flow immunoassay using shows a sensitivity of 97.70% (95.72%-99.34%) and specificity of 100% (100.00-100.00%). Conclusions Through comprehensive analysis of a large cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting up to 140 days, providing insight to immunity levels at later time points. We propose an alternative to RT-PCR positive status as a standard for assessing SARS-CoV-2 antibody assays and show strong performance metrics for the AbC-19 rapid test.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Laboratory evaluation of SARS-CoV-2 antibodies: detectable IgG up to 20 weeks post infection

Lj¹,

Js²,

Blighe³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Levels and styles of reporting the epidemic progress in each country vary considerably (2). Cases are dramatically under-reported and case definitions have changed significantly over time; therefore, the scientific and public health communities turned to serological surveys as a means to position populations along their expected epidemic timeline (3,4). Prospects that information gained from serological studies could resolve the true levels of population exposure to the virus, and thus provide valuable insights into COVID-19 lethality, were frustrated by apparent rapid declines in antibody levels following infection (5)(6)(7).…”

Section: Main Textmentioning

confidence: 99%

Levels of SARS-CoV-2 population exposure are considerably higher than suggested by seroprevalence surveys

Chen

Flegg

White

et al. 2021

Preprint

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Accurate knowledge of levels of prior population exposure will inform preparedness plans for subsequent SARS-CoV-2 epidemic waves and vaccination strategies. Serological studies can be used to estimate levels of past exposure and thus position populations in their epidemic timeline. To circumvent biases introduced by decaying antibody titers over time, population exposure estimation methods should account for seroreversion. Here, we present a new method that combines multiple datasets (serology, mortality, and virus positivity ratios) to estimate seroreversion time and infection fatality ratios and simultaneously infer population exposure levels. The results indicate that the average time to seroreversion is five months, meaning that true exposure may be more than double the current seroprevalence levels reported for several regions of England.SummarySARS-CoV-2 exposure in England could be double the reported seroprevalence, with implications for the impact of vaccines/other interventions.

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“…Following the initial genomic characterisation in December 2019, the immediate focus was on preventive measures to minimize the spread of infection. Extensive use of laboratory testing has been and remains a critical part of these measures despite its limitations [1][2][3] and cost. Simultaneously, there has been an intense research focus on the mechanisms underpinning coronavirus infectivity.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 (Covid-19): A short update on molecular biochemistry, pathology, diagnosis and therapeutic strategies

Ismail

2021

Ann Clin Biochem

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The ongoing coronavirus (covid-19) pandemic highlights the need for global scientific cooperation to advance our understanding of the immunological, molecular and biochemical mechanisms causing infection by this virus. Better understanding of key processes has allowed development of vaccines in record time, and of agents with the potential to treat and neutralise current and future coronavirus outbreaks. To date, clinically effective agents for prevention and treatment of covid-19 infections are limited. This review provides a brief synopsis regarding the molecular biology, pathology and laboratory tests commonly used in the diagnosis and prognosis of covid-19, as well as the development of vaccines and therapeutic strategies to manage its current and future mutations.

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Testing for SARS-CoV-2 antibodies

Cited by 89 publications

References 20 publications

Laboratory evaluation of SARS-CoV-2 antibodies: detectable IgG up to 20 weeks post infection

Laboratory evaluation of SARS-CoV-2 antibodies: detectable IgG up to 20 weeks post infection

Levels of SARS-CoV-2 population exposure are considerably higher than suggested by seroprevalence surveys

SARS-CoV-2 (Covid-19): A short update on molecular biochemistry, pathology, diagnosis and therapeutic strategies

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