by Kristina Fiore, Director of Enterprise & Investigative Reporting, MedPage Today August 3, 2022

A substantial proportion of COVID-19 patients who continue to test positive on a rapid antigen test after 5 days may still be infectious, according to a small study.

Of 17 patients who were tested for viral culture on day 6, 12 still had a positive antigen test, and six of these patients had culturable virus, a proxy for infectiousness, reported Lisa Cosimi, MD, of Brigham and Women's Hospital in Boston, and colleagues in JAMA Network Open.

These findings could have implications for current CDC guidelines that recommend ending isolation after 5 days if afebrile for 24 hours and symptoms are improving.

Cosimi said rapid antigen tests (RATs) correlate well with viral culture in the first several days of infection, so one might have expected the percentage of culturable samples to be higher. However, she noted, these tests haven't been validated for use in the later phases of infection, such as after day 5.

While previous studies have correlated antigen test positivity with culture positivity during early infection, there aren't much data on test positivity and culturable virus more than 5 days after infection, even though people can test positive for far longer.

"It's plausible that, similar to PCR testing, RATs are detecting viral shedding that is not actually capable of transmission," Cosimi told MedPage Today in an email. "Therefore, maintaining isolation through day 10 may unduly isolate a large number of individuals who are not still infectious."

"However, given these data, there is also a risk that individuals are leaving isolation while still infectious," she added. "We strongly agree with CDC's recommendation to wear a tight-fitting mask on days 6-10, especially if RAT positive, and to avoid areas where there is a high risk of transmission to others."

Cosimi and colleagues enrolled 40 people with COVID-19 (mean age 34) from January 5 to February 11, when Omicron BA.1 was the predominant strain in the Boston area. The majority of the participants (75%) had a positive rapid antigen test on day 6; only 10 participants had a negative test on day 6.

The researchers focused on a convenience sample of 17 individuals, collecting anterior nasal and oral swabs on day 6 to grow in culture, as culturable virus is currently the best proxy for transmissibility.

Of the six people who had culturable virus, two had improving symptoms, two had unchanged symptoms, and two never reported any symptoms.

None of the five people with a negative rapid antigen test on day 6 had positive cultures. In addition, seven of the nine people who had no symptoms on day 6 had negative culture results.

All patients in the study were negative by day 14, and the mean day of first negative rapid antigen test was 9.3 in those who'd ever had symptoms and 8.1 in those who'd never had symptoms.

Cosimi pointed to two other small studies that found culturable virus after day 5. One study found that 17% of vaccinated college students had culturable virus after day 5 from symptom onset, with the latest on day 12. Another found the median time to culture conversion to negative was 6 days after an initial diagnosis with a PCR test.

The researchers concluded that the data "suggest that a negative RAT result in individuals with residual symptoms could provide reassurance about ending isolation. However, a universal requirement of a negative RAT result may unduly extend isolation for those who are no longer infectious. Meanwhile, a recommendation to end isolation based solely on the presence of improving symptoms risks releasing culture-positive, potentially infectious individuals prematurely, underscoring the importance of proper mask wearing and avoidance of high-risk transmission venues through day 10."

The study was limited by its small cohort of mostly young, vaccinated, and non-hospitalized patients, and thus may not be generalizable to a wider population.

Kristina Fiore leads MedPage’s enterprise & investigative reporting team. She’s been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com. Follow

The authors reported financial relationships with Cell Signaling Technologies, Sherlock Biosciences, and Proof Diagnostics.

Source Reference: Cosimi LA, et al "Duration of symptoms and association with positive home rapid antigen test results after infection with SARS-CoV-2" JAMA Netw Open 2022; DOI: 10.1001/jamanetworkopen.2022.25331.

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