Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Systematic review and meta-analysis.</jats:p></jats:sec><jats:sec><jats:title>Data sources</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Eligibility criteria and data analysis</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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%).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Study registration</jats:title><jats:p>PROSPERO CRD42020179452.</jats:p></jats:sec>

Serological Determinants of COVID-19

“…The results of many studies showed that their global sensitivity, speci city, positive predictive value (PPV) and negative predictive value (NPV) were equivalent to the ELISA IgG/IgM or the CLIA IgG/IgM tests 44 . Similarly, to previous studies, we found accordance between the two analytical methods.…”

Antibody testing for coronavirus disease 2019: not ready for prime time

“…In a linked paper, Bastos and colleagues (doi:10.1136/bmj.m2516) provide a much needed review of the performance of serological assays to accurately detect antibodies to SARS-CoV-2 2. They meta-analyzed 40 studies according to type of antibody test (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), and chemiluminescent immunoassays (CLIAs)), and for each type, determined the average or pooled sensitivity and specificity and assessed the studies for risk of bias.…”

A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial.

“…Plasma collected from patients who have recovered from a SARS-CoV-2 infection can contain antiviral antibodies detectable through serological testing 2 . It is unclear to what extent these antibodies provide anti-viral protection, but at least a subset of patients presents with high titres of neutralizing antibodies, or with speci c potent antibodies irrespective of the titre 3 .…”