Pasadena, CA—Rapid at-home COVID-19 tests using a nasal swap often provide false negatives, suggesting someone is infection-free even if other parts of their respiratory tract have high viral loads.

That is according to new research from the California Institute of Technology (Caltech). The researchers tracked viral loads in three places in the human body: the nose, the throat, and the mouth. “Generally, we saw that most people have virus first appear in their throat and in saliva, and then, sometimes days later, in their nose,” explained coauthor Alexander Viloria Winnett, a biology graduate student. “Actually, each sample type from a single person follows its own distinct rise and fall of viral load, so it makes a big difference which sample type is used for testing.”

The report in Microbiology Spectrum pointed out that, earlier in the pandemic, medical professionals performed a deep nasal swab (polymerase chain reaction [PCR] rest), which was more sensitive but had two downsides—discomfort and slow results.

The at-home nasal rapid antigen tests can be performed without the assistance of a medical professional and provide results in as little as 15 minutes.

Yet, the researchers determined that most people had a delay of several days between when the virus first appeared in the throat or saliva and when it appeared in the nose where it could be detected by a swab. They advised that 15 out of 17 study participants had high and likely levels of the virus for at least 1 day prior to getting a positive antigen test.

“In one individual, levels of virus in throat swabs were extremely high and presumably infectious for almost 2 weeks while nasal-swab viral loads were undetectable or remained so low they would have been detected only by a highly sensitive PCR test,” said Natasha Shelby, PhD, the Caltech COVID-19 study’s administrator and a coauthor on the paper. “This individual never tested positive on her daily rapid antigen tests.”

Dr. Shelby pointed out that, in addition to only testing the nose, the rapid tests “have low sensitivity, which means they require a lot of virus to indicate a positive result. People assume that these tests will be positive when people are infectious, but we now know from numerous studies that this is not always true.”

“In a recent household transmission study of SARS-CoV-2, we found extreme differences in SARS-CoV-2 viral loads among paired saliva, anterior nares swab (ANS), and oropharyngeal swab specimens collected from the same time point,” according to the report.

Hypothesizing that the differences might hinder low–analytical-sensitivity assays (including antigen rapid diagnostic tests [Ag-RDTs]), the researchers evaluated daily at-home ANS Ag-RDTs (Quidel QuickVue) in a cross-sectional analysis of 228 individuals and a longitudinal analysis (throughout infection) of 17 individuals enrolled early in the course of infection.

With Ag-RDT results compared with reverse transcription-quantitative PCR results and high, presumably infectious viral loads (in each, or any, specimen type), the study found that the ANS Ag-RDT correctly detected only 44% of time points from infected individuals on cross-sectional analysis.

“From the longitudinal cohort, daily Ag-RDT clinical sensitivity was very low (<3%) during the early, preinfectious period of the infection,” the authors advised. “Further, the Ag-RDT detected ≤63% of presumably infectious time points. The poor observed clinical sensitivity of the Ag-RDT was similar to what was predicted based on quantitative ANS viral loads and the inferred limit of detection of the ANS Ag-RDT being evaluated, indicating high-quality self-sampling.”

They warned that nasal Ag-RDTs, even when used daily, “can miss individuals infected with the Omicron variant and even those presumably infectious.”

The researchers further cautioned that the poor clinical sensitivity to detect infectious individuals “is inconsistent with the commonly held view that daily Ag-RDTs have near-perfect detection of infectious individuals.”

Viloria Winnett said he hopes the Caltech COVID-19 study findings will spur the development of home testing kits that sample both the nose and throat. The tests are widely used in places such as the United Kingdom but are not authorized for use in the United States.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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