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 was performed to explore the heterogeneity. Results The pooled sensitivity for IgG (n = 17), IgM (n = 16) and IgG-IgM (n = 24) based LFIA tests were 0.5856, 0.4637 and 0.6886, respectively compared to rRT-PCR method. The pooled sensitivity for IgG (n = 9) and IgM (n = 10) based CLIA tests were 0.9311 and 0.8516, respectively compared to rRT-PCR. The pooled sensitivity the IgG (n = 10), IgM (n = 11) and IgG-IgM (n = 5) 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. Amongst 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 a 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 CRD42020179112

A systematic review and meta-analysis of the sensitivity of antibody tests for the laboratory confirmation of COVID-19

“…The pooled mean sensitivity obtained with CLIA IgM-IgG was significantly higher than LFIA IgM and CLIA IgG only ( Supplementary Table 4 ). Unlike previous studies that have reported lower sensitivities with the LFIA test method compared with the CLIA and ELISA based assays within each antibody class [ 14 , 15 , 77 , 78 ], our results show that LFIA tests do have a role to play in detecting antibodies to SARS-CoV-2. While LFIA IgM, 47.1% (95% CI: 39.77–54.48), had the lowest sensitivity: LFIA IgG, 78 % (95% CI: 72.71–82.48), performed marginally better than either CLIA IgG or IgM assays.…”

“…Our meta-analysis yielded high specificities ranging from 95.3% (95% CI: 91.75–96.9) to 99% (95% CI: 96.09–99.71) compared with the rRT-PCR. Similar studies have reported pooled specificities spanning from 95% (95% CI: 91–98) to 99.9% (97.78–100) [ 14 , 15 , 77 , 78 ]. Sensitivity estimates for within 7 days since onset of disease could not be evaluated because identified studies did not provide the data.…”

“…In LFIA tests, detecting the IgG seemed to be a better choice than assaying the IgM. The meta-analysis by Bastos et al and Vengesai et al reported higher pooled sensitivities with the CLIA IgG and LFIA IgG based serological assays compared with the respective IgM test methods albeit with overlapping 95% CIs, while with the ELISA methods higher positivity was obtained by detecting the IgM [ 14 , 15 ]. Regarding sensitivity within 7 days of symptom onset, our findings show that neither IgM nor IgG was a more sensitive marker for COVID-19 diagnosis.…”

“…Hence the use of LFIA tests in the diagnosis of COVID-19 has been questioned. The sensitivity of LFIA, CLIA and ELISA have been reported the lowest during the first week of symptom onset but peaked in the third week or later [ 14 , 15 ]. Even though the current evidence points to an increase in sensitivity later during infection, serological tests still result in many false negatives [ 14 ].…”

Serological testing for SARS-CoV-2 antibodies in clinical practice: a comparative diagnostic accuracy study

“…Sensitivities and specificities obtained were consistent across various patient subgroups. With these diagnostic accuracy measures obtained in a real-life clinical setting, we were able to fill a critical gap in knowledge, identified by many previous authors, systematic reviews, and institutions such as the WHO [2,5,9,10,20,[30][31][32].…”