Do you know how an infectious disease is really triggered? It mainly depends on two elements. On the one hand, the virulence factors of the microorganism responsible for the disease. On the other, of the genotypic and phenotypic characteristics of the infected organism.
The Covid-19, which we will talk about in this article, does not escape this dogma of medicine. We have all witnessed how infections caused by even the same variant of the virus have had fatal or very serious effects in some people and have gone unnoticed (asymptomatic) in others.
After almost two years of its appearance, there is already clear clinical evidence that some conditions, such as advanced age or high blood pressure, are associated with a worse prognosis of the infection.
However, we have little scientific data on the cellular and molecular mechanisms that determine that individuals with the same characteristics, apparently, suffer from the disease in such a disparate way.
How could science solve this crossroads?
Since the beginning of the pandemic, scientists have tried to identify phenotypic differences at the molecular level that explain why some individuals respond well to infection and others do not.
For this, different technical approaches have been used. Among them, proteomics techniques, that is, large-scale protein studies. These make it possible to detect, identify and even quantify almost all of the proteins in a given blood sample.
So it could recognize the set of proteins that are altered because of the viral infection in the most serious patients and try to understand why they are.
Usually the sample that is analyzed is the soluble fraction of the blood, that is, the serum. It is done this way because it is easy to obtain and because it reflects the immune and inflammatory state of the body.
Why does Covid-19 affect each person differently?
Just seven months after the start of the epidemic, the
first study which used proteomic techniques to analyze serum from Covid-19 patients.
This work revealed that the most seriously ill patients had elevated blood levels of a series of inflammatory mediators (C-reactive protein, serum amyeloid proteins and proteins of the complement system). Some of them are induced by interleukin 6, a target that is being used tocilizumab. This is a monoclonal antibody that blocks interleukin from binding to its receptor, preventing its effects.
The presence of high levels of inflammatory mediators in the blood is not something unique to Covid-19 and, to a certain extent, it was something to be expected. For this reason, since the first wave of the pandemic, critically ill patients have been treated with drugs that try to mitigate this exaggerated inflammatory response. For example, corticosteroids.
We still don’t know for sure why some individuals develop an oversized inflammatory response. But what is evident is that this response is closely associated with a poor prognosis in the evolution of Covid-19.
Proteomics at the Blood Coagulation Milestone
Furthermore, one of the most interesting findings that proteomics studies have confirmed is the dramatic alteration in the levels of factors that induce blood clotting.
Indeed, proteins such as fibrinogen, among others, are found in unusually high concentrations in critically ill patients. This is associated with a greater ease in forming clots. As a consequence, these patients are treated with anticoagulant agents to counteract the consequences of these alterations.
However, we do not yet know the exact molecular mechanism by which the virus manages to alter the complex system of clotting factors. Nor if this mechanism is the same that operates in the cardiovascular complications associated with the coronavirus or in the very rare cases of thrombosis detected in people vaccinated with the virus’s Spike protein.
These results have been subsequently confirmed by other studies, including the one published by a group from the University of the Balearic Islands and the Balearic Islands Health Research Institute Foundation (IDISBA), which we will discuss in this article.
A new use of proteomics techniques to predict gravity in three hours
In the same vein as proteomic techniques, in our recent study we have developed a new technology that would help predict the best or worst prognosis for Covid-19.
Although the method known as MALDI-TOF is not useful for identifying proteins directly from serum, it allows obtaining a quick overview of low molecular weight protein levels. Also of the major protein fragments present in a sample by means of their detection when excited by laser.
Thus, we have verified that this technology is capable of associating with great precision certain protein profiles to each of the three states of clinical severity in which Covid-19 is classified: critical, severe and mild.
However, what is most surprising is that the changes in protein profiles are detectable even 48 hours before the patient experiences the characteristic symptoms of worsening disease. Thus, the analysis of these profiles makes it possible to predict the evolution of the disease.
Prevent the severity of the disease in time
The analysis can be carried out in less than 3 hours. It only requires an instrument that today is present in most clinical microbiology laboratories of hospitals in the health network for the identification of microorganisms.
The transfer of this technology to the hospital, currently in progress, will allow anticipating the taking of therapeutic measures (to make them more effective) or improve the management of hospital resources.
As a whole, the results obtained in the laboratory thanks to the different variants of proteomic techniques have been transferred to patients admitted to the hospital.
This has been possible thanks to key elements on which to act with drugs already available and provide new diagnostic tools. In addition, they have made it possible to identify targets on which to continue investigating to increase our knowledge about the pathology of Covid-19 and its sequelae.
Sebastián Albertí Serrano. Professor of Microbiology. University of the Balearic Islands.
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