COVID-19 disease lies on a spectrum, ranging from completely asymptomatic to mild disease to severe and critical disease. Studies have shown that prolonged shedding or sporadic detection of SARS-CoV-2 RNA can occur long after symptom resolution. Adding to these clinical complexities is the demand for testing for SARS-CoV-2 at all stages of diseases, frequently driven by screening of asymptomatic persons, something that traditionally has not been performed for other viral respiratory diseases. This can lead to positive results from nucleic acid amplification tests (NAATs), such as RT-PCR, with late cycle threshold (CT) values near the test's limit of detection. In this commentary, we review unique attributes of COVID-19 and causes of NAAT late CT values. We provide interpretation considerations as well as strategies to aid in test interpretation.