Evaluation of recombinant nucleocapsid and spike proteins for serological diagnosis of novel coronavirus disease 2019 (COVID-19)

Zhang, Pingping; Gao, Qi; Wang, Tang; Yuan, Ke; Mo, Fei; Jia, Ruizhong; Liu, Wanbing; Liu, Lei; Zheng, Shangen; Liu, Yuzhen; Li, Luping; Wang, Yao; Xu, Lei; Hao, Kun; Li, Shiyue; Cui, Lin; Zhao, Yong

doi:10.1101/2020.03.17.20036954

“…In total, 4696 records based on screening of titles or abstracts and 235 after full text review were excluded. Forty studies totalling 73 study arms15161718192021222324252627282930313233343536373839404142434445464748495051525354 met the inclusion criteria. Table 1 summarises the studies by test method; the sum of the number of studies exceeds 40 because some evaluated more than one method.…”

Section: Resultsmentioning

confidence: 99%

“…Table 1 summarises the studies by test method; the sum of the number of studies exceeds 40 because some evaluated more than one method. Seventy per cent (28/40) of the studies were from China,16171819202122232425262728293031323334353839404145464748 8% (3/40) from Italy,153643 and the remainder from the United States (3/40),425052 Denmark (1/40),51 Spain (1/40),37 Sweden (1/40),53 Japan (1/40),44 the United Kingdom (1/40),49 and Germany (1/40) 5433…”

Section: Resultsmentioning

confidence: 99%

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Bastos

¹

,

Tavaziva

²

,

Abidi

³

et al. 2020

BMJ

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AbstractObjectiveTo determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).DesignSystematic review and meta-analysis.Data sourcesMedline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19.Eligibility criteria and data analysisEligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses.Main outcome measuresThe primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset.Results5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%).ConclusionHigher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests.Study registrationPROSPERO CRD42020179452.

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“…Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. The analyses also showed that tests that use the S antigen are more sensitive than N antigen-based tests probably due to higher sensitivity and earlier immune response to the S antigen 52 and more specific perhaps due to less cross-reactivity with less conserved regions of spike proteins existing in other coronaviruses (SARS-CoV) 17,55,64 . Combining N and S antigens further improves sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis

Kontou

¹

,

Braliou

²

,

Dimou

³

et al. 2020

Preprint

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With the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LFIA) that are based on immunochromatography. In total, we identified 38 eligible studies that include data from 7,848 individuals. The analyses showed that tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones, and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. All methods yielded high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods performed better in terms of sensitivity (90-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 86%. ELISA tests could be a safer choice at this stage of the pandemic. POC tests (LFIA), that are more attractive for large seroprevalence studies show high specificity but lower sensitivity and this should be taken into account when designing and performing seroprevalence studies.

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“…The sensitivity of the immunoassays for the presence of antibodies in human samples may depend on the viral titer and time of sample collected after viral infection; both factors impact circulating antibody concentration [77]. ELISA and chemiluminescence assays based on the antibodies have shown a sensitivity of 70-95% and 82-97% respectively [78][79][80]. A peptide luminescence method was developed with recombinant S protein to detect IgM and IgG antibody.…”

Section: Immunoassays For Antibody To Virusmentioning

confidence: 99%

“…The immunoassay-based rapid diagnostic test (RDT) kits, depending on the vendor type, are reported to have sensitivity in the range of 60-80% and selectivity of 85-100% at a confidence interval of 95% [57]. The RDTs that are LFIAs have shown 86% to 88% sensitivity and 90% to 99% specificity to detect total antibodies [78,79,81,82]. A study by Bendavid et al demonstrated 82% sensitivity and 99.5% specificity for detecting antibodies to SARS-CoV-2 tested in 3330 adults and children in Santa Clara County, CA, using LFIAs [29].…”

Section: Immunoassays For Antibody To Virusmentioning

confidence: 99%

Review of analytical performance of COVID-19 detection methods

Giri

¹

,

Pandey

²

,

Shrestha

³

et al. 2020

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In the recent SARS-CoV-2 pandemic, public health experts have emphasized testing, tracking infected people, and tracing their contacts as an effective strategy to reduce the spread of the virus. Several diagnostic methods are reported for detecting the coronavirus in clinical, research, and public health laboratories. Some tests detect the infection directly by detecting the viral RNA and other tests detect the infection indirectly by detecting the host antibodies. A diagnostic test during the pandemic should help make an appropriate clinical decision in a short period of time. Recently reported diagnostic methods for SARS-CoV-2 have varying throughput, batching capacity, requirement of infrastructure setting, analytical performance, and turnaround times ranging from a few minutes to several hours. These factors should be considered while selecting a reliable and rapid diagnostic method to help make an appropriate decision and prompt public health interventions. This paper reviews recent SARS-CoV-2 diagnostic methods published in journals and reports released by regulatory agencies. We compared the analytical efficiency including limit of detection, sensitivity, specificity, and throughput. In addition, we also looked into ease of use, affordability, and availability of accessories. Finally, we discuss the limitations of the methods and provide our perspectives on priorities for future test development.

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Evaluation of recombinant nucleocapsid and spike proteins for serological diagnosis of novel coronavirus disease 2019 (COVID-19)

Cited by 50 publications

References 19 publications

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis

Review of analytical performance of COVID-19 detection methods

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