Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis
Authors: Lisboa Bastos Mayara , Tavaziva Gamuchirai , Abidi Syed Kunal , Campbell Jonathon R , Haraoui Louis-Patrick , Johnston James C , Lan Zhiyi , Law Stephanie , MacLean Emily , Trajman Anete , Menzies Dick , Benedetti Andrea , Ahmad Khan Faiz 
Published: July 2020

Objective

To determine the diagnostic accuracy of
serological tests for coronavirus disease-2019
(covid-19).

Design

Systematic review and meta-analysis.

Data sources

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.

Eligibility criteria and data
analysis

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.

Main outcome measures

The 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.

Results

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% 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%).

Conclusion

Higher 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 registration

PROSPERO CRD42020179452.