Scientists from the University of Alberta, Canada, have developed a model to determine specific viral load loops for patients with true coronavirus syndrome 2 (SARS-CoV-2). The data obtained from this model can be used in other high-level models to assess the physiological and pathological effects of virus infection and to determine patient risks. The study is currently available on the medRxiv* preprint server.
Background
The newly emerged 2019 coronavirus infection (COVID-19) caused by SARS-CoV-2 has been found to cause a wide variety of symptoms, from mild cough and fever to severe lung and cardiovascular problems. . Like other viral infections, viral load or intracellular virus loading is a major determinant of disease severity in COVID-19 patients. Therefore, monitoring the viral load in a patient ‘s body is an essential procedure for the treatment of SARS-CoV-2 infection.
In general, the development of viruses within the body is divided into three stages. In the first stage immediately after the viral entry, a rapid and abstract increase in viral loading is observed, which is followed by a second stage of slow, gradual reduction and a third stage of reduction. fast, exponential in viral loading, leading to viral clearance. The length of each stage usually depends on the infection and pathogenity of the virus and the strength of the immune system of the infected person.
In the current study, the scientists have developed a simple model that determines specific viral load loops for patients.
![Normal curves of virus loading. Virus load (“titer”) is usually reported as a reduction value, TCID50, which is required to enter 50% of a particular cell culture in (A) full scale and (B) scale logarithmic. Shadow fields indicate the three stages in which we share the progress of virus loads. (C) Parameters of normal virus loading duty (1) according to loop curves A, B, D and E. Virus reported in [12] used in A and B. (DE) Comparison of the viral load curve from the viral target model (2) with the action of viral loads (1). A viral target curve showing a triphasic and biphasic response is shown in (D) and (E), respectively. Parameter values for the action of viral loads corresponding to the viral target model are in C. (F) The parameters of the target model (2) correspond to D and E.](https://i0.wp.com/d2jx2rerrg6sh3.cloudfront.net/image-handler/picture/2021/1/123-1.jpg?resize=560%2C269&ssl=1 "Normal curves of virus loading. Virus load (“titer”) is usually reported as a reduction value, TCID50, required to enter 50% of a particular cell culture in (A) full scale and (B) scale logarithmic. Shadow fields indicate the three stages in which we share the progress of virus loads. (C) Parameters of normal virus loading duty (1) according to loop curves A, B, D and E. Virus reported in [12] used in A and B. (DE) Comparison of the viral load curve from the viral target model (2) with the action of viral loads (1). A viral target curve showing a triphasic and biphasic response is shown in (D) and (E), respectively. Parameter values for the action of viral loads corresponding to the viral target model are in C. (F) The parameters of the target model (2) correspond to D and E.")
Normal curves of virus loading. Virus load (“titer”) is usually reported as a reduction value, TCID50, required to enter 50% of a particular cell culture in (A) full scale and (B) scale logarithmic. Shadow fields indicate the three stages in which we share the progress of virus loads. (C) Parameters of normal load activity of virus (1) according to virus loop curve A, B, D and E. [12] used in A and B. (DE) Comparison of the viral load curve from the viral target model (2) with the action of viral loads (1). Viral target loops showing triphasic and biphasic responses are shown in (D) and (E), respectively. Parameter values for the action of viral loads corresponding to the viral target model are in C. (F) The parameters of the target model (2) correspond to D and E.
Study design
To develop the model, they have considered each stage of infection progression at two intervals. The viral loop was developed as a result of three actions, representing three primary stages: the initial growth stage, the intermediate slow decay stage, and the final rapid decay stage.
They have added the action of viral loads to the viral titer data obtained from mice with influenza virus and humans and monkeys with SARS-CoV-2 infection.
Important comments
To determine the role of influenza A virus viral loads, the time series of titers of viral loads obtained from 10 mice with influenza virus was employed. By matching the model to the viral load data, the scientists have estimated that the approximate length of phase 1, phase 2, and phase 3 was 2.4 days, 3.2 days, and 1.3 days, respectively.
To determine the viral load activity of SARS-CoV-2 infection, the scientists have used viral load titers in 23 COVID-19 patients daily. They have seen a patient-to-patient difference in viral load over time, with some patients showing a long-term infection of 20 – 25 days and some showing a short-term infection of about ten days . However, the viral load action they developed has successfully described all three stages of viral infection for the majority of patients. This shows that the viral load model can easily account for the viral load loops for both short-term and long-term viral infections.
The scientists have also used viral load data obtained from 9 monkeys that had different doses of SARS-CoV-2. By weaving the action of viral loads into the data of infectious monkeys, they have found that the length of viral growth rate is similar among all monkeys, indicating that the size of the original virus is not a crucial diagnostic feature. Moreover, they have found that there is only one decay rate with greater decay rates in most monkeys. However, in some monkeys, a rapid, initial and second slow decay rates were observed. This distinction between biphasic and triphasic viral loads suggests effective functioning of the immune system in some monkeys.
Investigate meaning
A convenient and direct viral load action model was developed in the present study that can be easily based on viral load titer data of influenza A virus infection and SARS-CoV-2 infection. According to the scientists, this model has many important applications. The viral load loops obtained from this model can be used in another high-level model to study the pathological features of viral infection. In addition, the model can be used to estimate the overall length of viral infection and viral decay rates at a population level, which are critical steps for determining patient risks. Another important function of the model is that it can easily differentiate between fast and slow responders, which is crucial for identifying high and low risk people.
* Important message
medRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.