Can Testing Predict SARS-CoV-2 Infectivity? The Potential for Certain Methods To Be Surrogates for Replication-Competent Virus

Since the beginning of the COVID-19 pandemic, molecular methods (e.g., real-time PCR) have been the primary means of diagnosing the disease. It is now well established that molecular tests can continue to detect SARS-CoV-2 genomic RNA for weeks or months following the resolution of clinical illness. This has prompted public health agencies to recommend a symptom- and/or time-based strategy for discontinuation of isolation precautions, which, for hospitalized patients, results in significant use of personal protective equipment. Due to the inability of current molecular diagnostic assays to differentiate between the presence of remnant viral RNA (i.e., noninfectious) and replication-competent (i.e., infectious) virus, there has been interest in determining whether laboratory tests can be used to predict an individual's likelihood of transmitting the virus to others. This review will highlight what is currently known about the potential for existing assays, such as real-time PCR and antigen tests, to predict active viral infection. In addition, data on the performance of new methods, such as molecular tests targeting viral RNA intermediates (e.g., subgenomic RNA), will be discussed.