How Global Health Policies can Better Utilise Covid-19 Ct Values
Henry Kwan argues that a global standardisation of Covid-19 measures is sorely needed.
Currently, national policies in many countries take a hands-off or delegatory approach to standardising Ct-assays. Indeed, there are no requirements to standardise Ct-assays or introduce means for easy comparison between different tests. This is a missed opportunity for profound public health benefits, both nationally and internationally. To seize them, governments should instil national (and ultimately international) means of comparing Ct (cycle threshold) value for Covid-19 infections.
In the remainder of this piece, I explore the problems caused by the lack of test standardization and also the benefits of facilitating comparison. As it is impractical to have one single standardized test, public health policies should instead establish a scale to correlate / convert and compare the Ct values generated by different assays. The starting point would be to introduce a broad categorization of Ct values in terms of “high”, “medium” and “low” viral load.
Measuring the Ct value via PCR assays is a common way to detect Covid-19 infections. The higher the value, the lower the concentration of viral genetic material. In other words, a low Ct value indicates having a high viral load and a higher risk of transmission to others. This helps to identify people at high risk of transmission. Together with serology testing, they are the two major testing methods for determining Covid-19 infections.
Hands-off regulation: The absence of standardization and implications
However, current health policies have not fully utilized the potential of Ct values. In the US, the common practice is for laboratories to merely report back whether the outcome is positive or negative, with the Ct value not reported to submitters and providers. This is also the case in Canada and the UK, unless there is a specific request. The reason often given is that many countries have multiple PCR tests done by different labs.
Why can governments be said to have taken a hands-off approach? Each lab — rather than the governments — set their own cut-off / threshold for determining infection, because the assay design varies depending on “how sensitive the test is and how the test is designed”. In general, this includes factors such as “sensitivity (limit of detection), chemistry of reagents, gene targets, cycle parameters, analytical interpretive methods, sample preparation and extraction techniques”. Some PCR tests cannot even generate a Ct value by design. In other words, the Ct values generated by non-standardized assays cannot be compared, neither nationally and internationally.
As a result, for instance in Ireland, Carroll and McNamara noted that “there was a wide variation in Ct values for different assays for the same viral loads”, with deviation as great as 6.5 cycles. In the US, the deviation is even more significant with as much as 14 cycles. In contrast, other countries—such as India (cut-off at 35) and Qatar (cut-off at 30)—have issued governmental guidelines for the cut-off. Notably, the study from Qatar noted that they used multiple PCR assays from suppliers in Switzerland and the US. But there is no information on the comparability between the exact assays used.
National and international discrepancies in cut-offs can be confusing for both professionals and the general public. For example, they could lead to situations where a person is tested negative in one place but positive in another. This could hinder cross-border travel and understandings of lockdown measures. Furthermore, statistical comparisons for academic or public policy purposes are made more difficult.
Policies should require means for conversion and comparison
The great referential potential of Ct value is wasted simply because there is no standardization. That said, complete standardization of Ct value (both outcome and the test) would be difficult given the differences in the PCR assays mentioned above.
Instead, policymakers should push for a national (and ultimately international) scale to convert and compare the outcome. Professionals and scholars have not opposed the feasibility of the latter/ Instead, they have signalled their favour (see, e.g., Carroll and McNamara saying outcomes should not be compared “unless the Ct value is correlated”; the UK government saying that the values should not be “directly” compared).
The starting point is to introduce a categorization for comparison in terms of “High”, “Medium” and “Low” viral loads, as suggested by Tom and Mina (with whom other scholars like Carroll and McNamara concurred). This has similarly been advocated by others, such as Platten et al. who suggest classifying whether the outcome is an “acceptable low risk value”.
Allowing comparisons enhances transparency, understanding and oversight
Allowing comparison has profound public health benefits, both nationally and internationally. First and foremost, it allows the public to take an informed reference of their viral load in terms of Ct values. This is important because the current lack of comparability can easily cause confusion and misunderstanding amongst the public—e.g. whether a Ct value of 32 is infectious or not when there is international news reporting that a value higher than 30 is ok in some countries.
In the local context, it enhances the transparency of the process of setting Ct value cut-offs. As mentioned above, some governments (e.g. Ireland and the UK) have adopted a delegatory approach and allow labs to determine the cut-offs. However, this leads to less public oversight of the discretion involved. For instance, Jamal, Farooq and Bidari noted the occurrence of this issue in India, where despite the government’s recommended cut-off of 35, “certain laboratories were using a Ct value of 24” and this “created a dangerous situation because the patients with Ct values between 24 and 35, who would otherwise test positive, escaped further follow-up”.
In turn, standardisation will also strengthen international public health by fostering easier comparisons. The stronger transparency may indirectly tighten up Ct value cut-off setting processes in other countries, thereby reducing global discrepancies and facilitating domestic or international travel between borders.
Henry Kwan is a Fellow of the Royal Society for Public Health in the United Kingdom.
Photo by visionart.av