The Interpretation of SARS-CoV-2 Diagnostic Tests

Abstract

Testing for SARS-CoV-2 has attracted a tremendous amount of attention as a tool to manage the ongoing COVID-19 pandemic. Although diagnostic laboratory testing is used ubiquitously by physicians and encountered regularly by individuals receiving medical care, several aspects of test interpretation are incompletely understood by medical communities and the general population, creating a significant challenge in minimizing the damage caused by disease spread through informed decision making and proper testing utilization. Here, general principles of test interpretation are reviewed and applied to specific examples, such as whether asymptomatic individuals should be tested, what it means to test positive (or negative), and how to interpret tests for "immunity passports." Unexpectedly, the answers seem to run contrary to many of the popular narratives about testing as a tool for managing COVID-19. Although testing is an important and essential part of managing diseases such as COVID-19, improper utilization can have unintended negative consequences.

Figure 1

Current Sensitivity and Specificity of SARS-CoV-2 Tests Allow for Problems If Overinterpreted The sensitivity of RT-PCR is reported to be only ∼80% in practice. Thus, someone infected with SARS-CoV-2 may test negative. Thus, negative tests should not be overinterpreted for individuals who are likely to be positive by other indications. The specificity of serology tests may be 95%, which still suggests a 5% false positive rate. Thus, the testing of a population such as a workplace may falsely suggest 5% of the non-infected population has been infected.

Figure 2

Test Result Interpretation Is Largely Affected by Whether Other Factors Suggest the Tested Individual Is Infected with SARS-CoV-2 If the same exact RT-PCR test is given to 2 different individuals—one whose presentation is consistent with SARS-CoV-2 infection and one whose presentation is not—then the probability that a positive test indicates an infection with SARS-CoV-2 can vary greatly. For example, the individual whose presentation suggests a 90% chance of infection is >99% likely to have an infection if he or she tests positive and 65% likely to have an infection if he or she tests negative. The individual at low risk remains more likely not to have an infection if he or she tests positive, and the absolute reduction in the chance that he or she has a SARS-CoV-2 infection has reduced by <1%.

Figure 3

Immunity Passport Decisions Need to Consider More Factors Than the Presence of Antibodies In a hypothetical example, a 65-year-old and a 25-year-old are tested for antibodies to SARS-CoV-2. They have no known exposure, the local seroprevalence is 5%, and they receive a serology test with sensitivity and specificity of 95%. The 65-year-old tests positive, which has a 50% probability of being a true positive. The 25-year-old tests negative, which has a >99% chance of being a true negative. Even if we assume the 65-year-old has immunity to SARS-CoV-2 when antibodies are present (an overly aggressive assumption), the 25-year-old is still at less risk of death for a SARS-CoV-2 infection. The estimated risk of death for individuals 60–70 years old is 3.6% and 0.2% for individuals 20–30 years old. Thus, if we assume that the risk of the 65-year-old is zero when antibodies are present and 3.6% when they are not, then the overall risk, considering test results, is a 1.8% risk of death, which is nearly 10× the risk faced by the 25-year-old. Therefore, although test results are valuable sources of information, other factors need to be considered.