Coronavirus: The importance of viral load in disease management

Coronavirus: The importance of viral load in disease management. How much weight a person carries can have consequences for both themselves and others around them.

From the beginning of the pandemic and as the scientific community was still trying to understand the specifics of the new virus and the disease it caused, empirical observations by doctors correlated the disease with the magnitude of a person’s exposure to the virus. It is noteworthy that the medical and nursing staff of hospitals in China were more likely to get sick than the rest of the population precisely because of their overexposure to SARS-CoV-2. Obviously the above is not strange: it is clearly better for our immune system to deal with 100 thousand viral particles, than with 1 million viral particles.

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Differences per patient

Similarly, a positive diagnosis for the presence of the virus does not mean the same thing for everyone: there are patients who carry a higher viral load and others a much lower one. The reasons for this differentiation are many and varied and have to do with both the size of the initial infection and the genetic background as well as the function of each person’s immune system.

Scientists now want to use this quantitative component of a positive diagnosis to control the pandemic, as people with a higher viral load are more likely to become ill themselves and release more viral particles into the environment, which means they spread the disease more effectively.

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Reaction to cycles

But let’s start from the beginning: worldwide, the most reliable and widespread method of diagnosing COVID-19 is the molecular detection of the genetic material of the virus in nasopharyngeal samples of the subjects. As you can imagine, in a histological sample there is definitely the genetic material of the person being examined. The test is done to determine if in addition to the same genetic material there is also the genetic material of the virus. In order to “catch” the viral genetic material in the “sea” of human genetic material, the former is multiplied to make it visible. This selective multiplication of viral genetic material is carried out in successive cycles with the help of an enzyme, polymerase,

In fact, what is achieved with PCR is the exponential increase in the genetic material of the virus. Assuming that there is one molecule of viral genetic material in the sample (in fact there are many more), two will result from the first PCR cycle. From the second will emerge four. From the third will emerge eight and so on. It is obvious that the higher the number of viral molecules the PCR starts, the fewer multiplication cycles will be needed to make the result visible. According to scientists’ calculations, a sample that appears positive after 12 cycles of multiplication, starts with 10 million times more viral genetic material than the sample that requires 35 cycles to give a positive result!

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The special importance of the number of circles

This valuable information about the number of multiplication cycles required for a sample to appear positive is what scientists call a CT value (Cycle Threshold value) and the question is whether it should be used further. That is, if in the molecular test for the diagnosis of the virus, in addition to the positive or negative answer, the CT value should also be given.

Opinions differ: Proponents of her case have been working to make the actual transcript of this statement available online. In particular, recent studies have shown that patients with CT values ​​below 25 (and therefore with a high viral load) have an increased chance of becoming seriously ill or dying compared to patients with CT values ​​above 25.

Increased infectivity

In addition, a study by French researchers published last week in the journal Clinical Infectious Diseases confirmed the increased infectivity of patients with low CT scores. In particular, examining 3,790 samples of patients with known CT values, French scientists found that they could culture the virus in 70% of samples with CT values ​​below 25, while they were able to achieve the same in only 3% of samples with CT 35 and above. In practice, this means that the CT value could be used by the competent authorities to immediately identify the individuals who should be quarantined as a matter of priority and their contacts should be tracked.

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The controversy and the recommendations

The contradiction in this has to do with the fact that the CT value is not an absolute value. In fact, the same sample may give a different CT value if tested by two different laboratories, while for the same test subject there may be different CT values ​​if two different samples are taken. Finally, it has been observed that with the onset of symptoms many patients show low CT values ​​which then increase as the mobilization of the immune system rids the body of the virus. For the above reasons, the American College of Physicians, although it does not dispute the usefulness of the CT value, recommends its members to be careful with its interpretation.

That’s for now! Why the CT price debate continues…

An important finding for the seriously ill

Nothing is simple with regard to SARS-CoV-2, and the question of utilizing the CT value comes to add to a wide range of unknown parameters. It is worth noting, however, that researchers have recently shed light on the genetic characteristics of a portion of people who are seriously ill compared to others. In particular, two articles published in the journal Science, signed by extended research teams led by scientists at the Howard Hughes Medical Institute, cited findings that about 14% of critically ill people owe their condition to genetic factors. mutations or the presence of autoantibodies against interferons, proteins that are released by the body in the early stages of a viral infection to prevent the virus from spreading to the body.

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