A recent study posted to the medRxiv* preprint server evaluated the positivity rates of coronavirus disease 2019 (COVID-19) rapid antigen tests (RAT) in infected individuals.
The latest COVID-19 isolation guidelines announced by the United States (US) Centers for Disease Control (CDC) revised the isolation period to five days for non-immunocompromised people developing an asymptomatic or mild infection. The infected individuals must use tight-fitting face masks near other people during this period.
According to some studies, the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission is higher one day before the onset of symptoms and up to three days post-symptom-onset. While these results correspond to the period preceding the emergence of the SARS-CoV-2 Omicron variant, there is limited knowledge regarding the infectious phase of an individual in the Omicron period, given its enhanced transmissibility and extensive vaccination rates. Moreover, the optimal isolation duration for infected people is uncertain.
The present study assessed the performance of RATs after five days of initial confirmed COVID-19 diagnosis by quantifying the test positivity rate and correlating the findings with symptoms and viral culture positivity. Between January 5, 2022, and February 11, 2022, SARS-CoV-2-positive study participants wanting to return to work/campus within ten days of COVID-19 diagnosis were provided with home RAT kits. These participants could return if they remain asymptomatic and/or afebrile for 24 hours with a negative RAT result on any day after five days of initial diagnosis.
The participants were adults (≥18 years) affiliated with the Broad Institute of MIT and Harvard reporting a new COVID-19-positive test. They self-tested with the Flowflex RAT, which is approved for emergency use in asymptomatic infections, and were required to provide pictures of test results in addition to reporting symptoms until they were RAT-negative.
The researchers enrolled 40 individuals with a new COVID-19 diagnosis during the study period. The mean age of the participants was 32 years, and females constituted about 58% of them. All participants were vaccinated, with about 90% receiving a booster vaccine dose. Most (83%) individuals developed symptoms approximately 1.2 days before testing positive, and no participant required hospitalization. Cycle threshold (Ct) values were available for 29 individuals tested at the Broad Institute with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The mean Ct value was 26.5, and the median Ct was 28.9.
Ten participants had a negative RAT result on the sixth day; daily positive results declined steadily, and all participants were RAT-negative by day 14. There was no correlation between the first RAT-negative result and time, or time since vaccination and RAT result, and Ct value. Throughout the study period, 90 RATs were performed from the sixth day, and of these, 68% were positive; 10 participants asymptomatic on the sixth day were RAT-positive.
Anterior nasal (AN) and oral swabs were obtained from 17 individuals on the sixth day for the SARS-CoV-2 culture tests. Eight individuals were asymptomatic, 12 subjects were concurrently RAT-positive, and the remaining had a negative result. Six individuals were positive for viral culture and were contemporaneously RAT-positive on that day. Two of them were asymptomatic throughout, with two individuals reporting symptom improvement on day six and two others declaring no change in symptomology. The positive predictive value (PPV) for a symptomatic case with a positive RAT result being culture-positive was 57%. On the sixth day, the negative predictive value (NPV) was 100% for asymptomatic people with a RAT-negative result.
The authors noted that in the cohort of 17 participants with virus culture results, incorporating negative RAT results (with the culture-negative status as a proxy) for ending the isolation period would mean six individuals being isolated longer than needed. A strategy based on improving symptoms alone could risk the premature release of four infectious individuals with positive virus cultures and two individuals in (prolonged) isolation. Based on a negative RAT for asymptomatic cases, one individual would have been released, and the number of people in prolonged isolation could have been minimized to three.
Understanding the risk of transmission in the early stages of infection is critical to guiding policies for containing viral spread and lowering the isolation period for non-infectious individuals. The team observed that 75% of the participants were positive with RAT five days after SARS-CoV-2 infection, and one-third were positive on day 10 of COVID-19 diagnosis. RAT and viral culture positivity rates were poorly correlated with 50% PPV, while a strong correlation was noted with RAT negative results (NPV = 100%).
The sample size was small and included young, healthy vaccinated subjects with a mild infection, presumably the SARS-CoV-2 Omicron variant. Hence, these findings are likely to vary among older people depending on vaccination status and comorbidities. In conclusion, ending isolation on day six of infection could risk the premature release of infectious, virus culture-positive individuals.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.