Virus alert

Using high Ct value to rule out Covid is dangerous. During a pandemic, any person showing symptoms must take precautions including following quarantine rules.

Written by Ruta Patwardhan and Rohini Kelkar

The second wave of the Covid-19 pandemic seems to be abating. But many issues raised in the past two months remain relevant. Maharashtra was again the worst affected state, with Pune and Mumbai seeing a steep increase in both the number of cases, and the number of people dying due to the virus.

It was observed by the Maharashtra government that a few laboratories across the state were arbitrarily using a Ct value of 24 as the cut off, which meant that Ct values of 25 and above were reported as Covid-19 negative. The state government sought clarification from Indian Council of Medical Research (ICMR) regarding what would be an acceptable Ct value to declare a patient as negative.

To understand a Ct value, we must know how a RT-PCR test works. The test amplifies or increases the amount of viral genetic material present in the sample so that it can be detected by the RT-PCR instrument. To put it very simply, let us assume that there is one copy of viral genetic material present in a sample. This copy becomes two copies in the first cycle of RT-PCR test; two copies become four copies in the second cycle. This continues with the number of copies increasing exponentially during each cycle, till the number of copies generated reaches the level of detection.

Ct value or the cycle threshold value is the cycle number at which the viral genetic material is amplified enough to be detected by the instrument. If, for example, the viral genetic material is detected after 10 cycles, the Ct value is 10.

It’s reasonable then that if the sample already has a lot of viral particles, less number of cycles are sufficient to reach the level of detection. Conversely, if the sample has only a few viral particles, many cycles will be required till a detectable number of viral particles are generated.

Therefore, higher the viral load, less the Ct value and less the viral load, higher the Ct value.

Ct value limit for considering a patient as positive varies from kit to kit, and is generally given by the kit’s manufacturer after validation. As with any other test, it is advisable to follow the manufacturer guidelines while performing and interpreting a test. For most of the RT-PCR kits that are currently available, a Ct value of 35 is considered as the cut-off.

So, does a lower Ct value correspond with worse patient outcomes? It is important to know that the Ct value depends on a large number of factors such as how well the sample was collected, how soon it was transported, how soon it was tested, how it was stored till the time of testing, the kit and the instrument used, and even the stage of the infection at which the sample was collected. Ct value can show a lot of variation, even with samples collected on the same day. Hence, there cannot be a comparison of Ct value from one sample to another.

Though some studies have found that lower Ct values were associated with the worst forms of the disease, we do not have conclusive evidence about this. Given the myriad factors which can affect the Ct value, it is never advisable to rely on the Ct value alone for treating a patient.

Let’s go back to the Maharashtra government’s letter to ICMR. It sought clarification about the lower threshold for detection that was being used by some laboratories.

ICMR’s reply to the query advised on following the generally accepted Ct value for detection of positives, which is a Ct of 35. Using a lower threshold for detection would mean that a large number of patients with Ct values between 25 and 35 would be falsely considered negative. However, these patients, particularly those without any symptoms, can continue spreading the infection.

What does that mean from the patient’s perspective? In a pandemic, the development of symptoms should prompt patients to take all the precautions, without waiting for test results. Even when the test report is negative but patients show symptoms, they should quarantine themselves.

Any positive report, irrespective of the Ct value, should be treated with utmost seriousness. Patients should not be lulled into a false sense of security if the Ct value is above 25. They should monitor their symptoms closely and follow their consulting physician’s advice.

Patwardhan is consultant microbiologist, Metropolis Healthcare and Kelkar, consultant, clinical microbiologist and specialist, Metropolis Healthcare, Mumbai

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