- 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.
- Epidemiological Correlates of PCR Cycle Threshold Values in the Detection of SARS-CoV-2
Cycle threshold (Ct) values are lowest (corresponding to higher viral RNA concentration) soon after symptom onset and are significantly correlated with time elapsed since onset (P<0.001); within 7 days after symptom onset, the median Ct value was 26.5 compared with a median Ct value of 35.0 occurring 21 days after onset. Ct values were significantly lower among participants under 18 years of age (P=0.01) and those reporting upper respiratory symptoms at the time of sample collection (P=0.001) and were higher among participants reporting no symptoms (P=0.05). (Science Magazine Summary)
- Estimating Epidemiologic Dynamics from Single Cross-Sectional Viral Load Distributions (Not Peer Reviewed)
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.
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.
- False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications
- SARS-CoV-2 Nasopharyngeal Swab Testing—False-Negative Results From a Pervasive Anatomical Misconception
- Cerebrospinal Fluid Leak After Nasal Swab Testing for Coronavirus Disease 2019
“We conducted a head-to-head evaluation of ten point-of-care-style lateral flow assays (LFAs) and two laboratory-based enzyme-linked immunosorbent assays to detect anti-SARS-CoV-2 IgM and IgG antibodies in 5-d time intervals from symptom onset and studied the specificity of each assay in pre-coronavirus disease 2019 specimens. The percent of seropositive individuals increased with time, peaking in the latest time interval tested (>20 d after symptom onset). Test specificity ranged from 84.3% to 100.0% and was predominantly affected by variability in IgM results. LFA specificity could be increased by considering weak bands as negative, but this decreased detection of antibodies (sensitivity) in a subset of SARS-CoV-2 real-time PCR-positive cases. Our results underline the importance of seropositivity threshold determination and reader training for reliable LFA deployment. Although there was no standout serological assay, four tests achieved more than 80% positivity at later time points tested and more than 95% specificity.”
IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Currently available commercial LFIA devices do not perform sufficiently well for 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 first symptoms.
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.
Point of care (POC) test is highly sensitive and specific against RT-PCR. Time to result is 2.6 hour for POC versus 26.4 hours for standard lab RT-PCR. SARS-CoV-2 POC test reduces median time-to-bed placement by ∼6 hours in-hospital. SARS-CoV-2 POC improves indices of hospital functioning and patient care.
- CovidNudge: Assessing a Novel, Lab-Free, Point-of-Care Test for SARS-CoV-2 (CovidNudge): A Diagnostic Accuracy Study
In this small study, researchers compared home-collected versus clinician-collected nasopharyngeal swabs for COVID-19 testing. The two methods were comparable.
“In this mass-screening study including 1,924 individuals, the sensitivity of nucleic acid amplification testing with nasopharyngeal and saliva specimens were 86% (90%CI:77-93%) and 92% (90%CI:83-97%), respectively, with specificities greater than 99.9%. The true concordance probability between the nasopharyngeal and saliva tests was estimated at 0.998 (90%CI:0.996-0.999) on the estimated airport prevalence at 0.3%. In positive individuals, viral load was highly correlated between NPS and saliva. Both nasopharyngeal and saliva specimens had high sensitivity and specificity. Self-collected saliva is a valuable specimen to detect SARS-CoV-2 in mass screening of asymptomatic persons.”
SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols.