Current best evidence for clinical care (more info)
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.
| Discipline / Specialty Area | Score |
|---|---|
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Infectious Disease | |
While the rapid and accurate diagnosis of COVID-19 remains a vital issue to hospitalists, we rarely have choices as to which assay is available. It's not clear to me when more accurate LFIA devices might be available, but right now most of my colleagues are comfortable with the performances and limitations of the ELISA and rRT-PCR assays in widespread clinical use.
One important issue with the use of Abs for COVID-19 diagnosis, is whether they can be used to confirm diagnosis in patients with high clinical probability of COVID-19 but negative RT-PCR. Since in this review all analyses were performed with RT-PCR as the reference standard, this question has not been addressed. There were 5 studies which used a combination of clinical, epidemiological and radiological findings along with the RT-PCR as the reference standard. It would be very interesting to analyse theses studies separately to see whether Abs help when RT-PCR is negative.
This timely, well-conducted systematic review and meta-analysis of Covid-19 serologic tests appropriately insists on the limits and heterogeneity of their performances.