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. Spencer EA, Heneghan C.

https://www.cebm.net/study/diagnostic-accuracy-of-serological-tests-for-covid-19-systematic-review-and-meta-analysis/

Published on September 1, 2020

Reference Lisboa Bastos M, Tavaziva G, Abidi SK, et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ. 2020;370:m2516. Published 2020 Jul 1.  2020
Study type
Country Any
Setting Review and meta-analysis
Funding Details Grant (ECRF-R1-30) from the McGill Interdisciplinary Initiative in Infection and Immunity (MI4).
Transmission mode Testing
Exposures N/a

Bottom Line

Higher quality studies of the accuracy of serological tests for Covid-19 are needed. Current evidence indicates that they are insufficiently accurate for use in point-of-care testing for Covid-19.

Evidence Summary

5016 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% CI 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%).

What did they do?

The study aimed to determine the diagnostic accuracy of serological tests to detect antibodies for Covid-19, using a systematic review and meta-analysis.

Literature searches were in Medline, 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.

Eligible 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.

The primary outcome was overall sensitivity and specificity, stratified by method of serological testing:

  • enzyme linked immunosorbent assays (ELISAs)
  • lateral flow immunoassays (LFIAs)
  • 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.

Study reliability

The authors state that the evidence has high risks of bias, heterogeneity, and limited generalisability to point-of-care testing and to outpatient populations.

The authors also state:
“Cautious interpretation of specificity estimates is warranted for several reasons. Importantly, few data were available from people who were tested because of suspected SARS-CoV-2 infection; hence our overall pooled estimates might not be generalisable to people who need testing because of covid-19 symptoms. For CLIAs, the lower specificity among people with suspected covid-19 could be a spurious finding from a false negative RT-PCR result, given that the specificity for CLIAs was high among people with confirmed other viral infections. By contrast, for LFIAs, other viral infections could have contributed to the lower specificity in suspected covid-19.”

Additional limitations reported by the authors:
“we compared pooled estimates between different study populations. As such, the possibility of confounding exists (eg, from differences in timing of sampling between studies), explaining differences in sensitivity or specificity.”

Clearly defined setting Demographic characteristics described Follow-up length was sufficient Transmission outcomes assessed Main biases are taken into consideration
Yes Yes N/A N/A Partly

What else should I consider?

This study compared accuracy of serological testing using viral culture, which can be considered gold standard at this stage, and also PCR, which is unclear as a standard for Covid-19 identification.

About the authors

Carl Heneghan

Carl Heneghan

Carl is Professor of EBM & Director of CEBM at the University of Oxford. He is also a GP and tweets @carlheneghan. He has an active interest in discovering the truth behind health research findings

Elizabeth Spencer

Elizabeth Spencer

Dr Elizabeth Spencer; MMedSci, PhD. Epidemiologist, Nuffield Department for Primary Care Health Sciences, University of Oxford.