COOfHea project: a study for efficient therapies against the Covid-19

How do people react to Covid-19 infection?

The CoofHea project has produced a research in cooperation with the University of Bari Aldo Moro with the aim of identify some molecular mechanisms that can be exploited for the development of innovative and more efficient therapies against the Covid-19 or other viral infections.

Puglia Region entrusted this scientific study to the Genomics and Bioinformatics Laboratory and the Medical Genetics Laboratory of the University of Bari.

The final output of this work is a final report that can be downloaded here.

The background

The idea of ​​this study stemmed from an observation that draw immediately attention of the whole scientific community. Patients’ reaction to Covid-19 infection was extremely heterogeneous: someone remained almost totally asymptomatic, with colds, little cough, and fever, while other people had to be hospitalized in intensive care, with very high mortality rate.

Thus, the Puglia Region decided to sample a local population of 230 people and to characterize specific individual genetic heritage, in order to study all the possible reactions to a viral infection.

The applied Methodology

The two Departments of the University of Bari, led by Prof. Graziano Pesole and Prof. Nicoletta Resta, decided to focus on the 2% of the genome that is called the exome, which corresponds to the gene portion of the genome, namely the genes that code for proteins.

A targeted sequencing analysis allowed to obtain about 50 million base pairs for each with 2x coverage, which means that each position was covered 20 times. For each patient about a billion bases, 50 million x20 were collected. All the collected data were then included in libraries for sequencing and massive sequencing.

The sample population

The overall population (230 people from Puglia Region) was divided into three macro groups:

  • “Susceptible individuals”: those suffering a severe form of disease, especially among the young population.
  • “Resistors”: those people who, despite living in proximity to an infected and mildly of severely sick person, remained either completely negative or asymptomatic.
  • “Controls”: those who got mildly ill, which is the normality of the viral infection. These ones are the terms of reference of our comparison study.

The results and the future objectives

In the case of susceptible patients the observed genetic variants had damaged genes already known to be related to covid-19. Genes were damaged and these mutations were responsible for very severe forms of the disease.

Even in the case of the resistors, however, a large number of genes related to the pathways affected by the infection were inactivated or damaged. The technical term of this behaviour is “loss of action”, which means that a loss of function was related to greater resistance.

On the basis of these results, it was possible to understand the biological pathways in which these genes are involved. Subsequently, this finding will give the chance to quickly understand how to intervene, for example with a drug therapy, to induce the same responses in controls or susceptible people who do not have the characteristics we observed in the resistors.

The objective for the future is enlarging the sample population to further geographical areas and more diversified type of patients, so as to keep understanding the genetic response to Sars Cov2 infection, and to face possible future pandemics with greater readiness.