COVID-19 Clinical Resources and Pertinent Research
A regularly updated list of the most useful COVID-19 clinical resources, the most significant research publications, and reliable news. To contribute, click the plus button on the left. Short URL: bit.ly/C19Res

Testing

  1. CEBM: COVID-19 Testing and Correlation with Infectious Virus, Cycle Thresholds, and Analytical Sensitivity
    Molecular detection of SARS-CoV-2 RNA does not mean infectious virus is present. The use of Ct values and clinical symptoms in combination with PCR testing for SARS-CoV-2 provides a more accurate assessment of the potential for infectious virus shedding.
  2. 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.
  3. 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.
  4. COVID-19 Testing: One Size Does Not Fit All
    Testing is a central pillar of clinical and public health response to global health emergencies, including the COVID-19 pandemic. Nearly all testing modalities have a role, and the one-size-fits-all approach to testing by many western countries has failed.
  5. 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)
  6. Antigen Rapid Tests, Nasopharyngeal PCR and Saliva PCR to Detect SARS-CoV-2: A Prospective Comparative Clinical Trial (Not Peer Reviewed)
    “The high performance of rapid diagnostic [antigen] tests allows rapid identification of COVID cases with immediate isolation of the vast majority of contagious individuals. RDT could be a game changer in primary care practices, and even more so in resource-constrained settings. PCR on saliva can replace nasopharyngeal PCR.”
  7. 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.
  8. 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.
  9. Evaluation of SARS-CoV-2 Serology Assays Reveals a Range of Test Performance
    “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.”
  10. Antibody Testing for COVID-19: A Report from the National COVID Scientific Advisory Panel
    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.
  11. Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review
    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.
  12. Point of Care Nucleic Acid Testing for SARS-CoV-2 in Hospitalized Patients: A Clinical Validation Trial and Implementation Study
    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.
  13. Comparison of Unsupervised Home Self-collected Midnasal Swabs with Clinician-Collected Nasopharyngeal Swabs for Detection of SARS-CoV-2 Infection
    In this small study, researchers compared home-collected versus clinician-collected nasopharyngeal swabs for COVID-19 testing. The two methods were comparable.
  14. The Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal Swabs
    “Thirty-seven studies with 7,332 paired samples were included. Against a reference standard of a positive result on either sample, the sensitivity of saliva was 3.4 percentage points lower than that of nasopharyngeal swabs. Among persons with previously confirmed SARS-CoV-2 infection, saliva’s sensitivity was 1.5 percentage points higher than that of nasopharyngeal swabs. Among persons without a previous SARS-CoV-2 diagnosis, saliva was 7.9 percentage points less sensitive. In this subgroup, if testing 100 000 persons with a SARS-CoV-2 prevalence of 1%, nasopharyngeal swabs would detect 79 more persons with SARS-CoV-2 than saliva, but with an incremental cost per additional infection detected of $8,093.”
  15. Cell-Based Culture of SARS-CoV-2 Informs Infectivity and Safe De-Isolation Assessments during COVID-19
    SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols.
  16. Modeling the Effectiveness of Olfactory Testing to Limit SARS-2-CoV Transmission (Not Peer Reviewed)
    Evaluation of an alternative strategy based on the monitoring of olfactory dysfunction, a symptom identified in 76-83% of SARS-CoV-2 infections—including those that are otherwise asymptomatic—when a standardized olfaction test is used. The authors model how screening for olfactory dysfunction, with reflexive molecular tests, could be beneficial in reducing community spread of SARS-CoV-2 by varying testing frequency and the prevalence, duration, and onset time of olfactory dysfunction and believe that self-monitoring olfactory dysfunction could reduce spread via regular screening.
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