New review of the evidence suggests PCR cycle threshold may be key

Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from pre and asymptomatic infected individuals. A systematic review
Clinical Microbiology and Infection – Available online 29 October 2021

New review of the evidence suggests PCR cycle threshold may be key to predicting infectiousness of people with asymptomatic and pre-symptomatic COVID-19.

The results suggest that PCR ‘Cycle thresholds’ could be the key to determining if someone who is asymptomatic may be able to infect others or not, and therefore deciding what measures should be put in place to prevent further transmission.

The findings confirm that a proportion of asymptomatic and pre-symptomatic people can pass on COVID-19 to others, while remaining apparently unaffected themselves, but this is far more likely to happen in people who have a low PCR ‘cycle threshold’.

In most commonly used COVID PCR tests, a positive result is given if a fluorescent signal develops after a number of ‘amplification’ cycles. The cycle threshold (Ct) is the number of amplification cycles required for the fluorescent signal to become strong enough to confirm a positive result. Because of the way PCR works, the more virus in a sample to start with, the fewer cycles are needed for a signal to be detected – the lower the Ct value.

A low Ct value is associated with  a high viral load. This means the amount of virus in a given sample was  high, and therefore the infected person is more likely to go on to infect others.

From the UK

“In the UK, by design, we carry out a large amount of asymptomatic testing, but we rarely ,if ever, report on an individual’s Ct numbers of  these tests. If we look at these findings in the context of reducing the amount of testing done in the UK, for example, it could be that by reporting people’s Ct numbers, we could better determine if someone should isolate or not. 

This would have multiple positive effects on both people, such as saving them the worry of being notified they may have been in contact with someone infected, and society, by stopping people needlessly having to isolate and all the problems this  causes people and communities as they go about their daily lives.”

The proportion of asymptomatic people who may have been transmissible ranged from 18% (in cruise ship passengers) to 86% (in army barracks), depending on the study population. As some of the studies focussed on ‘captive’ populations, such as cruise ships or care homes, these levels are likely to vary depending on a number of population and environmental factors.

“This finding may go some way to explain the apparent paradox of why the number of people with COVID in care homes rose after lockdowns began. These could well have been people who were infected before the lockdown began, it just took longer for symptoms to manifest or be recognised, and the person be tested.”

It was not possible from the studies included to estimate how long a person might remain contagious.

The results from this systematic review from Centre for Evidence-based Medicine based at the University of Oxford are part of a larger project supported by the World Health Organization and the NIHR School of Primary Care Research (SPCR) , providing regularly updated summaries and evaluations of the data and evidence on SARs-CoV-2 transmissibility, including areas such as airborne, contact and droplet, orofecal, and fomite transmission (inanimate objects that might pass on infection, like door handles and phones).

 “As these are ‘living’ reviews, each update we make narrows the sphere of uncertainty a bit more, meaning we can be increasingly confident in what the data says, and what it’s real-world implications may be. The overall aim of this ongoing research is to enable policy makers to make reasonable and reliable decisions around transmission probabilities.”