Research on the interaction of SARS-CoV-2 and the host at the proteomic level
One year after the first documented cases of SARS-CoV-2 infection, current knowledge about its pathogenesis still remains limited, so therapies for severe cases are mostly speculative. The pandemic, says Jesús Vázquez, has shown that there is an “urgent need for technologies that can accelerate our understanding of this type of new infectious diseases.”
One of those tools is proteomics. The proteomic study of circulating proteins in the blood, emphasizes Dr. Vázquez, offers a unique opportunity “not only to find markers to measure the severity of the disease and to make clinical decisions, but also to identify preventive strategies and discover therapeutic targets.”
The work, that the group led by Jesús Vázquez from the CNIC, is carrying out in the Proteomics facilities is included in a macro-project being developed by ProteoRed, a network platform of the Carlos III Health Institute made up of 22 proteomics laboratories distributed throughout Spain. The project, for which Dr. Fernando Corrales is responsible, seeks to articulate the full potential of proteomics in our country, optimizing resources and experience to provide the molecular basis for new diagnostic, therapeutic and vaccination strategies necessary to control the epidemic. Dr. Vázquez’s group has applied its experience in clinical proteomics in two specific subprojects.
In one of them, in collaboration with basic and clinical researchers from the National Paraplegic Hospital of Toledo, they have demonstrated the key role of heparin, an anticoagulant drug used mainly to prevent and treat venous thrombosis, for patients with spinal cord injury due to SARS-CoV-2 infection, where the clinical characteristics of the infection differ slightly from those observed in the general population.
Cough and asthenia are the most frequent symptoms in this population. Furthermore, patients infected with spinal cord injury rarely have complications that require admission to an Intensive Care Unit, unlike the general population. Therefore, there is a clear need to understand from a molecular perspective how COVID-19 affects patients with spinal cord injury.
The data provided by this project, which has been published in the scientific magazine Journal of Personalized Medicine, shows a significant correlation between the proteins found differentially existing in the bloodstream and the heparin dose, suggesting a key role of this drug in the response to COVID-19 infection in patients with spinal cord injury.
Although the number of patients with spinal cord injury is limited, the data from this study may shed light on new therapeutic options to improve their management and possibly also in the general population.
This study offers a unique opportunity “not only to find markers to measure the severity of the disease and to make clinical decisions, but also to identify preventive strategies and discover therapeutic targets,” emphasizes Dr. Vázquez
In the other subproject, the group of Dr. Vázquez, in which Estefanía Núñez, Patricia Baena and Enrique Calvo also participate, is comparing the proteome of the blood plasma of those controlled individuals admitted to the hospital with varying degrees of severity and even deaths from the virus in a cohort provided by the Biobank of the Aragonese Institute of Health Sciences, with the idea of elucidating the mechanisms and response to infection. Although they are not published yet, Dr. Vázquez acknowledges, the preliminary results support previous studies and demonstrate that COVID-19 has a strong impact on the plasma proteome.
Thus, he assures, “SARS-CoV-2 infection produces a pattern of changes in the plasma proteome very similar to those observed in other cohorts analyzed in China and Germany, although specific differences are also detected.”
This early data shows that IL-6-mediated activation of the acute phase response is the most reproducible alteration detected in plasma. In addition, the infection also produces a decrease in the levels of immunoprotective apolipoproteins (HDL) and alterations in the coagulation cascade. On the other hand, changes are also detected in some plasma proteins that reflect lesions in the lung and kidney.
Therefore, the researchers assure that bloodstream proteomics provides objective information about host response and disease progression and also identifies potential targets for therapeutic action.
“Our data,” adds Dr. Vázquez, “suggest that monitoring of specific proteins can help detect which recently diagnosed COVID-19 cases are more likely to progress to severe disease and assess the specific tissue damage produced by the virus.”
Researchers are currently validating these results through targeted analysis of the most relevant plasma proteins in another cohort.
“These experiments suggest that proteomics would be a very useful tool for the diagnosis and monitoring of patients in future pandemics,” adds the CNIC researcher.
