- CDC: Interim Guidelines for COVID-19 Antibody Testing
Recommendations on the use of serologic tests to determine protective immunity and infectiousness among persons recently infected with SAR-CoV-2 will be updated as new information becomes available.
- Interpreting Diagnostic Tests for SARS-CoV-2
This Viewpoint describes how to interpret 2 types of diagnostic tests commonly in use for SARS-CoV-2 infections—reverse transcriptase–polymerase chain reaction (RT-PCR) and IgM and IgG enzyme-linked immunosorbent assay (ELISA)—and how the results may vary over time.
- Diagnostic Accuracy of Serological Tests for COVID-19: Systematic Review and Meta-analysis
The authors of this meta-analysis of 40 studies evaluated the diagnostic accuracy of serological tests for COVID-19. There was a high risk of patient selection bias and bias from the performance or interpretation of the serological test. The pooled sensitivity was 84.3% for enzyme-linked immunosorbent assays measuring IgG or IgM, 66.0% for lateral flow immunoassays (LFIAs), and 97.8% for chemiluminescent immunoassays. The pooled specificity was >96% for all tests, but most of the samples used for estimating specificity were from populations not suspected of having COVID-19. The pooled sensitivity of LFIAs was lower in commercial kits compared with non-commercial tests. The sensitivity at week 3 after symptom onset was significantly higher than at week 1.
- Estimating False-negative Detection Rate of SARS-CoV-2 by RT-PCR (Not Peer Reviewed)
Testing throat and nasal swabs by RT-PCR is not guaranteed to yield a positive result for SARS-CoV-2 infection and this probability decreases with time since the onset of symptoms. In a single test of someone who first developed symptoms ten days ago, there’s a 33% chance of a false negative with a nasopharyngeal swab and 53% chance of a false negative with an oropharyngeal swab.
“We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV2 antibodies. The specimen set comprised 130 plasma or serum samples from 80 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with COVID-19…Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.8-94.8%. No consistent cross-reactivity was observed. Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals.”
The performance of current LFIA devices is inadequate for most individual patient applications. ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following symptoms onset.
SARS-CoV-2 testing on respiratory specimens has imperfect sensitivity and is limited in capacity. Antibody testing can aid in diagnosing RT-PCR–negative patients who present later during disease. However, antibody testing should not be the only test for diagnosing acute COVID-19. Serologic testing may help to clarify the determinants of SARS-CoV-2 immunity and aid in vaccine development.