As the COVID-19 pandemic progresses, there is an increasing need for rapid, accessible assays for SARS-CoV-2 detection. We present a clinical evaluation and real-world implementation of the INDICAID COVID-19 rapid antigen test (INDICAID rapid test). A multisite clinical evaluation of the INDICAID rapid test using prospectively collected nasal (bilateral anterior) swab samples from symptomatic subjects was performed. The INDICAID rapid test demonstrated a positive percent agreement (PPA) and negative percent agreement (NPA) of 85.3% (95% confidence interval [95% CI], 75.6% to 91.6%) and 94.9% (95% CI, 91.6% to 96.9%), respectively, compared to laboratory-based reverse transcriptase PCR (RT-PCR) using nasal specimens.

The INDICAID rapid test was then implemented at COVID-19 outbreak screening centers in Hong Kong as part of a testing algorithm (termed “dual-track”) to screen asymptomatic individuals for prioritization for confirmatory RT-PCR testing. In one approach, preliminary positive INDICAID rapid test results triggered expedited processing for laboratory-based RT-PCR, reducing the average time to confirmatory result from 10.85 h to 7.0 h. In a second approach, preliminary positive results triggered subsequent testing with an onsite rapid RT-PCR, reducing the average time to confirmatory result to 0.84 h. In 22,994 asymptomatic patients, the INDICAID rapid test demonstrated a PPA of 84.2% (95% CI, 69.6% to 92.6%) and an NPA of 99.9% (95% CI, 99.9% to 100%) compared to laboratory-based RT-PCR INDICAID Rapid Antigen Test Instructions using combined nasal/oropharyngeal specimens. The INDICAID rapid test has excellent performance compared to laboratory-based RT-PCR testing and, when used in tandem with RT-PCR, reduces the time to confirmatory positive result.

 Laboratory-based RT-PCR, the current gold standard for COVID-19 testing, can require a turnaround time of 24 to 48 h from sample collection to result.

The delayed time to result limits the effectiveness of centralized RT-PCR testing to reduce transmission and stem potential outbreaks. To address this, we conducted a thorough evaluation of the INDICAID COVID-19 rapid antigen test, a 20-minute rapid antigen test, in both symptomatic and asymptomatic populations. The INDICAID rapid test demonstrated high sensitivity and specificity with RT-PCR as the comparator method. A dual-track testing algorithm was also evaluated utilizing the INDICAID rapid test to screen for preliminary positive patients, whose samples were then prioritized for RT-PCR testing. The dual-track method demonstrated significant improvements in expediting the reporting of positive RT-PCR test results compared to standard RT-PCR testing without prioritization, offering an improved strategy for community testing and controlling SARS-CoV-2 outbreaks.

• The global SARS-CoV-2 pandemic has continued despite implementation of significant public health measures (1).
• Over 155 million worldwide cases of COVID-19 and over 3 million COVID-19 deaths have been reported as of May 2021. Rapid identification of SARS-CoV-2 infection, patient isolation, and contact tracing are essential for disease containment (2).
• The current gold standard for detecting SARS-CoV-2 is reverse transcriptase PCR (RT-PCR) (3). While RT-PCR can detect nucleic acids from SARS-CoV-2 with high sensitivity, RT-PCR requires equipment and special training and can take days for results to be available following sample collection (4).
• Due to the transmissibility of SARS-CoV-2 (basic reproductive number R₀ of 2.87), long turnaround times for results may lead to a high number of avoidable transmissions (5, 6).
• In contrast, lateral flow immunoassays (LFAs) are an inexpensive testing solution that can be used at point-of-care settings, do not require laboratory equipment, and can generate results quickly.
• However, the performance of LFA-based SARS-CoV-2 rapid antigen tests in community testing settings can vary significantly .
• In this study, we evaluated the clinical performance of the LFA-based INDICAID COVID-19 rapid antigen test (INDICAID rapid test) by PHASE Scientific International Ltd. A prospective multisite clinical study was performed in symptomatic patient populations in point-of-care (POC) community testing sites in the United States.
• The performance of the INDICAID rapid test was also evaluated in COVID-19 outbreak screening centers in Hong Kong as a part of an algorithm testing approach (termed “dual-track”) to screen for COVID-19-positive patients prior to RT-PCR testing in asymptomatic patient populations.

Prospective multisite clinical evaluation of the INDICAID COVID-19 rapid antigen test.

 In total, 83 participants with at least two COVID-19 symptoms were enrolled at the San Francisco, CA and Oakland, CA sites. Two participants were excluded from the analysis due to lost samples during transport for RT-PCR. Of the 81 participant specimens analyzed, 44.4% were from female participants (Table S1), with a median age of 32 years (interquartile range [IQR], 25, 44). The most frequently reported symptoms were muscle/body ache (61.7%), congestion/runny nose (60.5%), fatigue (56.8%), and headache (53.1%). The breakdown of duration of symptoms was 1 to 2 days in 37 participants (45.7%), 3 to 4 days in 38 participants (46.9%), and 5 days in 6 participants (7.4%).

San Fernando population characteristics.

In total, 270 participants with at least one COVID-19 symptom were enrolled at the San Fernando, CA site. Two participants were excluded from the analysis due to lost or spilled samples during transport for RT-PCR. Of the 268 participant specimens analyzed, 52.6% were from female participants (Table S2), and the median age was 35 years (IQR, 24, 50). The most frequently reported symptoms were sore throat (60.8%), headache (60.1%), congestion/runny nose (59.0%), and cough (54.9%). The distribution of duration of symptoms was 1 to 2 days in 109 participants (40.7%), 3 to 4 days in 127 participants (47.4%), and 5 days in 32 participants (11.9%).

Performance of the INDICAID COVID-19 rapid antigen test in symptomatic patients.

Of the total 329 participant specimens included in the analyses, 75 tested positive with the comparator laboratory-based RT-PCR test. The mean cycle threshold value was 20.79 ± 6.39.

The INDICAID rapid test demonstrated a PPA of 85.3% (95% confidence interval [95% CI], 75.6% to 91.6%) and an NPA of 94.9% (95% CI, 91.6% to 96.9%) when sample collection was conducted by a health care professional. There was a total of 11 false-negative INDICAID results that were not concordant with RT-PCR results; the mean threshold cycle (C_T) value of the false-negative INDICAID specimens was 32.56 ± 4.59.