Viral cultures for COVID-19 infectivity assessment – a systematic review
Jefferson T., Spencer EA., Brassey J., Heneghan C.
<h4>Summary</h4> <h4>Objective</h4> to review of the evidence from studies comparing SARS-CoV-2 culture, the best indicator of current infection and infectiousness with the results of reverse transcriptase polymerase chain reaction (RT-PCR). <h4>Methods</h4> We searched LitCovid, medRxiv, Google Scholar and Google for Covid-19 for ‘viral culture’ or ‘viral replication’ and associated synonyms up to 18 th August 2020. We carried out citation matching and included studies reporting attempts to culture or observe SARS-CoV-2 matching the with cutoffs for RT-PCR positivity. One reviewer extracted data for each study and a second review checked end edited the extraction and summarised the narratively by sample: fecal, respiratory, environment or mixed. Where necessary we wrote to corresponding authors of the included or background papers for additional information. We assessed quality using a modified QUADAS 2 risk of bias tool. This review is part of an Open Evidence Review on Transmission Dynamics of COVID-19. Summaries of the included studies and the protocol (v1) are available at: https://www.cebm.net/evidence-synthesis/transmission-dynamics-of-covid-19/ . Searches are updated every 2 weeks. <h4>Results</h4> We included 17 studies reporting 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, cycle threshold (as a proxy for viral load) and symptom severity. 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 limiting our current ability to quantify the relationship between the variables and ultimately the usefulness of PCR use for assessing infectiousness of patients. Ifectivity appears to decline after about a week of viral shedding around the cycle threshold value of 24. <h4>Conclusion</h4> 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.