A systematic and meta-analysis review on the diagnostic accuracy of antibodies in the serological diagnosis of COVID-19.

Abstract

Background: Serological testing based on different antibody types are an alternative method being used to diagnose SARS-CoV-2 and has the potential of having higher diagnostic accuracy compared to the current gold standard rRT-PCR. Therefore, the objective of this review was to evaluate the diagnostic accuracy of IgG and IgM based point-of-care (POC) lateral flow immunoassay (LFIA), chemiluminescence enzyme immunoassay (CLIA), fluorescence enzyme-linked immunoassay (FIA) and ELISA systems that detect SARS-CoV-2 antigens.Method: A systematic literature search was carried out in PubMed, Medline complete and MedRxiv. Studies evaluating the diagnostic accuracy of serological assays for SARS-CoV-2 were eligible. Study selection and data-extraction were performed by two authors independently. QUADAS-2 checklist tool was used to assess the quality of the studies. The bivariate model and the hierarchical summary receiver operating characteristic curve model were performed to evaluate the diagnostic accuracy of the serological tests. Subgroup meta-analysis analyses was performed to explore the heterogeneity. Results: The pooled sensitivity for IgG, IgM and IgG-IgM based LFIA tests were 0.5856, 0.4637 and 0.6886, respectively compared to rRT-PCR method. The pooled sensitivity for IgG and IgM based CLIA tests were 0.9311 and 0.8516, respectively compared to rRT-PCR. The pooled sensitivity the IgG, IgM and IgG-IgM based ELISA tests were 0.8292, 0.8388 and 0.8531 respectively compared to rRT-PCR. All tests displayed high specificities ranging from 0.9693 to 0.9991. Among the evaluated tests, IgG based CLIA expressed the highest sensitivity signifying its accurate detection of the largest proportion of infections identified by rRT-PCR. ELISA and CLIA tests performed better in terms of sensitivity compared to LFIA. IgG based tests performed better compared to IgM except for the ELISA. Conclusions: We report that IgG-IgM based ELISA tests have the best overall diagnostic test accuracy. 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 independently. Given the poor performances of the current LFIA devices there is need for more research on the development of highly sensitivity and specific POC LFIA that are adequate for most individual patient applications and attractive for large sero-prevalence studies.Systematic review registration: PROSPERO Registration Number is: CRD42020179112

A comparative review of immunoassays for COVID-19 detection

“…As stated in WHO guideline, COVID-19 cases are confirmed by detection of unique sequences of the virus RNA using nucleic acid amplification tests (NAAT) such as real-time reverse transcription-polymerase chain reaction (rRT-PCR) in sputum, throat swabs, and secretions of the lower respiratory tract [6,7]. rRT-PCR, the reference standard method, diagnoses SARS-CoV-2 infection with high sensitivity and accuracy in the acute phase of COVID-19 illness [4].…”

“…However, rRT-PCR is timeconsuming and needs 4-6 h to be performed. It also needs costly specialist equipment, skillful laboratory staff for sample preparation and testing [7]. Furthermore, false-negative results due to low viral load in the upper respiratory may occur using RT-PCR analysis.…”

“…Additionally, the peak of viral load in upper respiratory tract secretions is within the first week of symptoms and can become undetectable by 14 days post-symptom onset [4,7]. Furthermore, problems in different steps of real-time RT-PCR, including sampling, RNA extraction, and PCR amplification, may result in failure in detecting COVID-19 patients by realtime RT-PCR.…”

SARS-COV-2 IgG and IgM Antibodies in Cancer Patients

“…There is extremely limited information on the Pishtaz Teb SARS-CoV-2 ELISA kit in international literature. Different types of ELISA tests targeting at different targets can result in different sensitivity and specificity (Vengesai et al, 2021;Huber et al, 2021). False positive is also a possible problem (Vengesai et al, 2021;Huber et al, 2021).…”

“…Different types of ELISA tests targeting at different targets can result in different sensitivity and specificity (Vengesai et al, 2021;Huber et al, 2021). False positive is also a possible problem (Vengesai et al, 2021;Huber et al, 2021). For further generalization of the finding for disease control plan in any setting, it is necessary to have a validation on diagnostic property of the diagnostic test.…”