From the height of the COVID-19 pandemic in March 2020 until the end of 2021, Canadian researchers conducted a diagnostic survey on the accuracy and effectiveness of SARS-CoV-2 nucleic acid amplification tests (NAATs), finding that their diagnostic sensitivity was high and that the results did not vary significantly by symptom duration.
The diagnostic sensitivity of these molecular tests suggests that one negative test result can effectively rule out SARS-CoV-2 infection for most patients, the researchers said.
“Gaining a better understanding of the clinical diagnostic test performance of NAATs in association with time since symptom onset and disease prevalence may help clinicians correctly interpret diagnostic test results, develop rational testing strategies, and avoid unnecessary repeated testing,” noted the researchers in their paper published on Wednesday in Infectious Diseases.
The study, which was led by researchers at the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN), involved 132,760 eligible patients and was evenly split between men and women. The median age of the patients was 57. Nearly 13% of these patients tested positive for SARS-CoV-2 within 14 days of their first NAAT, totaling 17,174 patients. The diagnostic sensitivity of the SARS-CoV-2 NAAT was 96.2% of all tests performed.
Of the 17,174 SARS-CoV-2–positive patients, 538 (3.1%) had an initially negative test result. Of those 538 patients with an initial negative test result, 434 (80.7%) tested positive within 14 days and were thus considered to have had at least one false-negative test result. All other patients tested positive after the follow-up period and were not considered to have had an initial false-negative test result.
The strength of the study, according to the researchers, was that it included enrollment of a consecutive sample of patients presenting to the emergency department, including those being admitted to the hospital and frequently undergoing repeated testing. This uniformity of patients tested in emergency departments afforded the study the ability to maintain a control for health access variables, which would be difficult to control in data sets containing the test results of both community- and hospital-based test sites.
“We used a composite reference standard that included all of the tests a patient had undergone, reporting the diagnostic test characteristics of the first test recorded, similar to prior studies but using a much larger sample size,” noted the researchers in their report. “We were able to perform sensitivity analyses, excluding asymptomatic patients and excluding patients who may be tested at regular intervals for screening purposes owing to their work or living situation.”
Despite this inherent strength of the study, the researchers do concede some limitations. One of the primary issues was that the data were collected retrospectively. This meant there was no way to capture information on the quality of the specimen.
One of the other limitations is an outgrowth of this retrospective collection. The researchers were limited in ascertaining a truly independent criterion standard, such as repeated testing for the same patient by a different laboratory.
“Despite these limitations, we believe our study provides a robust clinical estimation of NAAT sensitivity and can guide emergency department physicians and admitting teams in their interpretation of diagnostic test results at the time patients present,” the researchers concluded.
They added: “The high diagnostic sensitivity of the NAAT suggests that one negative test result can effectively rule out SARS-CoV-2 infection for most patients presenting to the emergency department, including those being tested at admission. Only patients with a very high clinical pretest probability and an initially negative test result warrant repeated testing.”