Viral cultures for COVID-19 infectivity assessment – a systematic review (Update 4)

Abstract
We report the results of a review of the evidence from studies comparing SARS-CoV-2 culture with reverse transcriptase polymerase chain reaction (rt-PCR), as viral culture represents the best indicator of current infection and infectiousness of the isolate. We identified fourteen studies succeeding in culturing or observing tissue invasion by SARS-CoV in sputum, naso or oropharyngeal, urine, stool and environmental samples from patients diagnosed with Covid-19. The data are suggestive of a relation between the time from collection of a specimen to test, copy threshold, and symptom severity, but the quality of the studies was moderate with lack of standardised reporting and lack of testing of PCR against viral culture or infectivity in animals. This limits our current ability to quantify the relationship between viral load, cycle threshold and viable virus detection and ultimately the usefulness of PCR use for assessing infectiousness of patients. Prospective routine testing of reference and culture specimens are necessary for each country involved in the pandemic to establish the usefulness and reliability of PCR for Covid-19 and its relation to patients factors such as date of onset of symptoms and copy threshold, in order to help predict infectivity.