RT-PCR: Does the CT Value of Above 24 Mean You Are Not Infectious?
The ICMR clearly states that it does not recommend COVID-19 patients to rely on numerical CT values.
A term related to the 'gold standard' RT PCR tests to detect the novel coronavirus has got a lot of attention. From a viral video by an Indian cardiologist, to Biocon's head Kiran Mazumdar Shaw, everyone is talking about the Cycle Threshold Value (CT Value) of the test and its role in deciding whether you can infect someone else or how contagious you are. This value is not indicated in your test report, but you can ask for it.
What Is This CT Value? Will A Person With Higher CT Value Not Be Contagious?
Dr Shahid Jameel, Virologist and Director at Trivedi School of Biosciences, Ashoka University, reveals in a conversation with FIT, that the RT-PCR test, ie, polymerase chain reaction test, examines the viral DNA or RNA to check the amount of molecules in it. There are many cycles in this test. DNA or RNA molecules are doubled in every cycle.
These tests are amplification tests - because the molecules in the sample are very small, the virus can be detected only after amplification in some cycles.
The CT value indicates the number of cycles needed for the virus to be detected. Due to amplification, a negative sample also starts giving non-specific positive signals in 40 cycles. Therefore, if the number is less than 40, the sample is considered positive.
CT value is a type of virus concentration. The higher the concentration, the lesser are the number of cycles needed for the virus can be detected. It is believed that if the sample concentration is higher, then the CT value will be less, indicating that the sample is more contagious.
It is being claimed in many news reports that even if the report is positive for the RT-PCR test, patients who have a CT value of more than 24 will not spread the infection.
Dr. Shahid Jameel falsifies such claims. He says that if someone with a CT value of 30 is roaming without a mask, then they are more likely to spread the virus than an infected person with a 22 CT value who stays isolated. In such a situation, fixing the cutoff at 24 can mislead people.
What Are ICMR's Guidelines on CT Value?
The Indian Council of Medical Research’s latest guideline released on August 8 says that estimating infectivity based on CT value may prove to be wrong and may lead to a false perception of safety.
The ICMR clearly states that it does not recommend COVID-19 patients to rely on numerical CT values to determine infectiousness and patient management protocols.
The guideline states-
There are no reliable studies to definitively prove a direct correlation between disease severity / infectiousness and Ct values. Viral load does not have much role in patient management.
Ct values differ from one kit to the other. Comparability of Ct values among different kits is a challenge as our labs are using a mixed basket of kits now with different Ct cut-offs and different gene targets.
Ct values also depend on how the sample has been collected. A poorly collected sample may reflect inappropriate Ct values. Besides, Ct values are also determined by technical competence of the person performing the test, calibration of equipment and pipettes and analytical skills of the interpreters.
Ct values between nasal and oropharyngeal specimens collected from the same individual may differ. - Similarly, temperature of transportation as well as time taken from collection to receipt in the lab can also adversely impact Ct values.
Samples from asymptomatic/mild cases show Ct values similar to those who develop severe disease.
Patients in early symptomatic stage may show a high Ct value which may subsequently change. In such cases, high Ct values will give a false sense of security.
Severity of COVID-19 disease largely depends on host factors besides the viral load. Some patients with low viral load may land up in very severe disease due to triggering of the immunological responses. Hence, again high Ct value may give a false sense of security.
Moreover, the RT-PCR test presently being conducted is qualitative in nature. Ct values may give a rough estimate of viral load. However, more specialized standards are required for quantitative assays which are currently unavailable for SARS-CoV-2.
A study published on medRxiv (MedArchive) has said that infectivity is less for CT values below 24. But this journal clearly states that there is a preliminary report of pre-print work printed in medRxiv (MedArchive), which has not been peer-reviewed. These reports should not be relied upon to guide clinical practice or health-related behaviour and should not be reported as established information in the news media.
According to a brief report published in the European Journal of Clinical Microbiology and Infectious Diseases, a CT value above 33–34 is not contagious and those patients can be discharged from the hospital.
Can the Severity of Illness Also Be Measured By CT Value?
Dr Jameel says that it has been generally seen that for cases wherein the disease is serious, the concentration of the virus is also higher. However, there have also been cases in which the concentration of virus was more but the disease was not serious. Disease severity does not have a direct correlation with the concentration of virus, and cannot be assessed from the CT value.
Having a high CT value does not mean that the patient can stop following the safety precautions for COVID-19.
“The PCR test is a difficult test. It should not be over-interpreted. It only tells whether the person is COVID-positive or not more accurately. It can compare two patients and indicate who is more infectious. But there is no confirmation that a person with CT value above 24 will not spread the infection. “Dr Shahid Jameel
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