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.

Pathogenesis‐directed therapy of 2019 novel coronavirus disease

“…Similarly, viral cultures of respiratory specimens have been found to be positive for 8–18 days with an average time of 10 days in patients with mild forms of COVID‐19 and for up to 32 days in patients with severe COVID‐19 267–270 . Clearly, SARS‐CoV‐2 has been cultured from many clinical samples 270 . Moreover, viable SARS‐CoV‐2 has been cultured from the air in a hospital room 271 .…”

“…It is important to realize that positive cultures of SARS‐CoV‐2 from the upper respiratory tract are found less frequently than RT‐PCR positive upper respiratory tract samples. Lower respiratory tract infections and stool cultures appear to have viable SARS‐CoV‐2 for approximately 1 month 267–270 . Antiviral therapy aimed at reducing the SARS‐CoV‐2 viral load would clearly benefit COVID‐19 patients as well as potentially reducing the spread to others.…”

Operation Moonshot proposals are scientifically unsound

“…One fundamental challenge is that proper evaluation of any point-of-care test destined for mass screening requires a robust and reliable way to identify true infectiousness: we need a reference standard against which the new test’s performance can be compared. Viral culture is one option, but culture based tests are hard to run and have high failure rates 5…”

“…It correlates with symptoms,4 and people with low Ct values (indicating more viral material) are those most likely to be infectious 5. Using a low maximum Ct value (around 3056) has been suggested to reduce problematic detection of dead virus,6 but it will also miss early infection and rising infectiousness in both presymptomatic and symptomatic people. The measurement error of Ct values is non-trivial, and measurements vary between manufacturers and laboratories 7.…”

Covid-19: Government faces criticism over £500m plan to pilot mass testing

“…Tom Jefferson, an epidemiologist for the Nordic Cochrane Centre and coauthor of a preprint paper examining viral cultures for assessing covid-19 infectivity,3 said that, while evidence showed that PCR tests were effective, the number of false positives they yielded must be taken into account when deploying them.…”