In a letter dated April 05, 2021, Dr Balram Bhargava, Director General and Secretary, Health Research, Indian Council of Medical Research (ICMR) wrote that a Ct value cut-off of 35 with a good sigmoidal real-time RT PCR curve is acceptable.
“It is not at all advisable to lower the Ct-value of an RT-PCR test for determining if a sample is COVID positive as this would lead to missing several infectious patients and increase the disease transmission rate,” he said in the letter.
This letter was in a response to the Maharashtra government that was seeking clarification on whether to treat a patient as COVID negative if the Ct value of the sample is more than 24.
What is Ct-value?
Ct-value stands for Cycle threshold value.
As per ICMR, the Ct-value during an RT-PCR test determines if the sample collected is COVID positive or negative.
How is Ct-value measured?
The RNA extracted from the sample of a patient is converted into DNA, which is then amplified to create copies of DNA. During the process of amplification, DNA goes through several cycles to detect the virus. These number of cycles form the cycle threshold (Ct-value) of an RT-PCR test that tells after how many cycles the virus was detected.
The ICMR has put forward a Ct-value cut-off of 35 as the acceptable measure to determine if a sample is COVID-positive or negative.
Why a Ct-value cut-off of 35 is acceptable?
Dr Bhargava in the letter mentioned that ICMR, after processing inputs from different virology labs across the country, has arrived at a single Ct-value cut-off of 35 with a good sigmoidal real-time RT PCR curve.
A patient with a Ct-value of 35 or below would be considered positive. This means the virus was detected after 35 cycles or earlier. Whereas, if the Ct-value comes back more than 35 then the patient would be considered negative.
Put simply, the chances of the virus going undetected is higher when the sample is run through a lesser number of cycles. A higher Ct-value of 35 compared to 24 would help in detecting more infectious persons.
Therefore, Dr Bhargava in the letter said that it is not at all advisable to lower the Ct-value of an RT-PCR test for determining if a sample is COVID positive as this would lead to missing several infectious patients and increase the disease transmission rate.
The globally accepted Ct-value cut off for COVID-19 is between 35 and 40.
What is the correlation between a Ct-value and the severity of disease?
There is no correlation. The ICMR states that there are no reliable studies to definitively prove any direct correlation between Ct-values and severity of COVID-19 disease.
Should one rely on the Ct-value as the final determinant of COVID-19 disease?
No. It has been noted that a patient with a low Ct-value would ideally have a higher viral load but could still be asymptomatic.
Whereas, some patients with high Ct-values and low viral load landed up showing severe symptoms of the disease due to change in immunological responses.
The ICMR recommends that one should not rely entirely on the Ct-values for determining the infectiousness of COVID-19 patients.
The Ct-value of the samples collected from the throat and nasal specimens of the same individual may vary.
Ct-values also differ from kits to kits, and how the sample has been collected and interpreted by analysts. A poorly collected sample will show inappropriate Ct-values.
The duration in between from the time of collection to reaching the lab and temperature of transportation can adversely impact the Ct-values.
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