What is the Ct value in a Coronavirus COVID test report?

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The third wave of COVID-19 has us all in its clutches right now. The number of COVID-infected patients is increasing. While some of us go to testing centers for confirmation, a large number of others are tested at home. The presence of infection is determined by the Ct value in all testing methodologies.

A Ct value appears on every COVID-19 test report. The Ct value cutoff is used to establish whether or not a person is COVID positive. Last year, the Maharashtra state government sought the Centre for clarification on the Ct value cutoff and whether an asymptomatic person with a Ct value of greater than 24 can be treated as a cancer patient. The state administration stated in the letter that this is due to the ICMR, NITI Aayog, and NCDC holding opposing ideas and Ct values.

Following deliberation and feedback from virology laboratories around the country, the central government responded that it had chosen to set a single Ct value cut-off.

To assess whether a person is COVID positive or not, the government has set the Ct value at 35.

A Ct value of less than 35 indicates that the person tested is COVID positive and should take medication and self-isolate as soon as possible to prevent the coronavirus from spreading further.

A Ct result greater than 35 indicates that the person being tested is COVID negative and can only self-isolate if there are other COVID positive people around. To determine COVID infection, the Ct value is fixed between 35 and 40 on a global scale.

So, how does the Ct value determine whether or not you have an infection?

The cycle threshold is represented by the Ct value. The Ct value determines the detectable level of the virus in a particular sample during the RT-PCR test, which is used to establish if a person is COVID positive or negative. The RNA from the sample is taken and converted to DNA, which is subsequently amplified or multiplied in RT PCR. To determine the viral load, this multiplication occurs across a number of cycles.

If the virus is discovered after only a few cycles, the body has a high viral burden. The Ct value is inversely related to the quantity of viral load in the human body in this way. The viral load decreases as the Ct value decreases, and the viral load increases as the Ct value decreases.

Is the infection's severity determined by the Ct value?

This is still an open question.

According to studies, the clinical importance of viral load is unreliable since viral levels in pre-symptomatic, asymptomatic, and symptomatic patients are similar.

Ct value, on the other hand, is considered by several researchers to be a possible criterion for determining severity. "It's acceptable to assert that having a higher viral load is associated with being more infectious," Monica Gandhi, an infectious diseases specialist at the University of California, San Francisco, said based on her research analysis of 3790 samples.

Gandhi believes that having access to Ct values is beneficial, but she also believes that a high viral load does not always imply sickness, as nearly 40% of people remain healthy after catching the disease.

In a research published by Science, Michael Mina argues that contact tracing, which is now thought to be a major technique for halting the chain of transmission, should be performed in the order of Ct values. According to him, contact tracing for people with high viral loads should be prioritized over those with low viral loads or a higher Ct value. "We need to stop thinking of people as positive or negative and start thinking about how positive they are," says a physician and epidemiologist at Harvard University's T.H. Chan School of Public Health, emphasizing the relevance of the Ct value in establishing an individual's infection level.

While it is questionable whether the Ct value alone can predict the risks, severity, and infection level in a person, many physicians and researchers consider it to be one of the many indicators that can help identify the infection's dynamics.

"Having the CT value is not the only thing I will use as a physician," Chanu Rhee adds. Similarly, a team of Chinese researchers discovered that viral load was negatively correlated with lymphocyte count but positively correlated with neutrophil count and C-reactive protein, which is associated with inflammation, a key feature of COVID-19 infection, in a study on the correlation between viral load or Ct value and COVID-19 infection progression. They noted that while viral load tended to increase and Ct value declined in certain patients throughout the transition from mild to severe cases, this was not the main cause of illness progression, citing study limitations.

What is the source of this disagreement?

"Unfortunately, raw Ct data, inadequate normalization references, or even non-standardization are being frequently considered," researchers write in the publication "Misinterpretation of viral load in COVID-19 clinical outcomes." "Knowledge of viral load is critical for developing antiviral treatment, immunization, and COVID-19 epidemiological control methods." Furthermore, identifying individuals with high viral loads will help researchers better understand risk factors like age, comorbidities, the severity of symptoms, and hypoxia, as well as determine the need for hospitalization," they write. "However, cycle threshold (Ct) values alone are frequently utilized as viral load markers in a large number of developing investigations, which may be a mistake ." Misinterpratation of Ct values is attributed to a variety of sample types, quantities of starting material for RT-qPCR, discrepancies among commercial detection kits, experimental circumstances, and real-time equipment for COVID-19 diagnosis, according to researchers. If the sample is collected from different areas of the body, the Ct values may differ in the same person. Ct values from nasal and oropharyngeal specimens taken from the same person may vary. "Ct readings are also affected by how the sample was obtained. Inadequate Ct values may be shown in a poorly obtained sample. Ct levels are also influenced by the technical competency of the individual doing the test, the calibration of equipment and pipettes, and the interpreters' analytical skills, according to the government.

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