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It was possible -- albeit rare -- for people not infected with SARS-CoV-2 to have persistent false positive rapid antigen COVID-19 tests, longitudinal data showed.

Among a large cohort of over 11,000 people, 1.7% had at least one false-positive COVID-19 rapid antigen test despite concurrent negative molecular tests, according to a brief report in the .

Most of those people had incidental false positive tests -- meaning they also had at least one negative rapid antigen test during the study period -- but 13 people had persistent false-positive COVID-19 rapid antigen tests with no negative tests, Apurv Soni, MD, PhD, of the University of Massachusetts Chan Medical School in Worcester, and colleagues reported.

"It is important to note that this is an extremely rare phenomenon -- in our report about 2% of participants tested [falsely] positive," Soni commented to MedPage Today in an email. "That is a similar false-positive rate reported for most antigen tests."

False negative results are known to occur fairly frequently with rapid antigen COVID-19 tests and, to a lesser extent, with the more accurate RT-PCR tests. False positives are thought to be much less common.

Soni said that false positive COVID-19 antigen test results have not been previously described before as a potential systematic issue. "There have been sporadic reports of lot-specific tests malfunctioning, but what we observed was independent of lots and test types," she explained.

Her group reported that certain groups may be more prone to getting these false positives.

Twelve of the 13 people with persistent false positive tests were women and all but one had used the Quidel QuickVue test.

Notably, six of the 13 people reported having an autoimmune disorder versus 10 out of the 178 with tests that were incidentally positive (OR, 14.4, 95% CI 3.2-59.9). Of the six individuals with autoimmune disorders, two had rheumatoid arthritis, one had Sjögren's syndrome, one had lupus and antisynthetase syndrome, and two had unidentified autoimmune disorders.

One potential explanation for the persistent false-positive tests among people with autoimmune diseases is that rheumatoid factor is known to cross-react with test antibodies, the authors explained. This cross-reactivity "could potentially occur in any patient who has a condition characterized by circulating rheumatoid factor."

"Now that we have this information, the physicians who care for such patients -- largely rheumatologists -- can inform their patients that if they think they might have COVID, they will have to do the more definitive PCR test, because the at-home test is not going to be reliable" in patients with autoimmune diseases, William Schaffner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, commented to MedPage Today.

"Although these rapid tests are convenient for the community, clinicians should always use clinical judgment when interpreting the test," Kruti Yagnik, DO, an infectious diseases specialist from Cleveland Clinic Indian River Hospital in Vero Beach, Florida, said in an interview. "If a patient does have an autoimmune disease, especially one with high levels of rheumatoid factor, definitely take that into account."

The report was based on two longitudinal cohort studies in which 11,297 participants had serial rapid antigen tests paired with RT-PCR tests for SARS-CoV-2 infection over 76,610 total days of testing. Researchers considered an antigen test result as a false positive if there was a corresponding negative RT-PCR test from anterior nasal samples obtained within 48 hours.

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