Researchers address variability of disease severity in respiratory tract infections

Is it possible to predict the course of a viral respiratory tract infection - for instance one caused by a coronavirus - based on individual patient characteristics? This question will be addressed by Dr. Victor Corman and his junior research group at Charité - Universitätsmedizin Berlin.

Submitted for approval last year, this research endeavor has taken on a new level of significance within the context of the current pandemic. The project will be funded by the Federal Ministry of Education and Research (BMBF) and has been allocated close to € 2 million over five years.

Viral respiratory tract infections are the most common type of infection in humans. Adults are affected approximately three times a year, children about six times a year. Most infections are mild. In some cases, however, they can lead to severe pneumonia, which can be fatal.

One question increasingly being asked since the start of the COVID-19 pandemic - and not just by experts - is: why is there such variability in disease severity, and are there individual patient characteristics that could be used to predict disease severity?

It was back in 2019 that Dr. Victor Corman, a researcher and clinician from the Institute of Virology on Campus Charité Mitte, made the study of these issues his long-term research goal - and the extremely common coronaviruses and picornaviruses the targets of his work.

He submitted his research proposal, entitled 'VARIPath', for funding under the BMBF's 'Junior Research Groups in Infection Research' program, and he was successful.

It has since become clear that Dr. Corman showed a remarkable degree of foresight in submitting his proposal, and that the ability to predict disease severity in respiratory tract infections represents a true clinical need.

In his pursuit of the ability to predict disease progression, the German Center for Infection Research (DZIF) researcher and Deputy Director of the National Consultation Laboratory for Coronaviruses at Charité will take a two-pronged approach.

His research group will study characteristics of both viral pathogens and the immune systems of those infected.

Whenever a respiratory virus replicates inside its human host, this will produce changes in the virus population. We want to find out whether characteristics of the virus populations can be used to predict disease progression in those who have been infected."

Dr. Victor Corman, Researcher and Clinician, Institute of Virology

The physician will use state-of-the-art high-throughput sequencing techniques to analyze in detail how viruses evolve inside their host patients. His research will focus on picornaviruses and coronaviruses, both of which store their genetic information in the form of RNA but show very different rates of mutational change.

While coronaviruses mutate very slowly, picornaviruses show a substantially faster rate of genetic change. Dr. Corman's original plans were limited to the study of well-known and widely spread coronaviruses such as HCoV-NL63 or HCoV-OC43. These have now been expanded to include the novel coronavirus, SARS-CoV-2.

In a parallel series of experiments, the researcher will study how host immune response characteristics differ in individual patients. Dr. Corman will use genetic analysis to map out which viral surface structures are targeted by specific immune cells known as B-cells and T-cells.

Further plans include the study of the body's antibody response and the release of a group of immune mediators known as cytokines.

"For all of these parameters, we will then check whether they enable us to predict, for instance, incapacity to work, secondary bacterial infections or ICU admissions," explains Dr. Corman. He adds: "Predictive parameters such as these could help us to adapt treatment strategies early on and have a positive impact on prognosis.

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