COVID-19 and Personalised Medicine

29 October 2020 – Professor Yazdan Yazdanpanah and his colleague Dr Olivier Robineau share with ICPerMed their first lessons learned on the health crisis and the contribution of personalised medicine approaches to fight infectious diseases through the light of the COVID-19 pandemic.

The SARS-COV-2 epidemic has and will continue to affect millions of people. In the context of a rapidly spreading new virus, it is urgent to take measures to limit its spread and to develop therapeutic solutions that can be used on a large scale. Thus, personalised medicine (PM) could appear to be a secondary issue in this world health emergency. However, the great variability in the evolution of the epidemic and the extremely polymorphic nature of patients' clinical course confirm that there are no simple, universal solutions to the pandemic in terms of both public health and therapeutic management. More generally, the management of epidemics and emerging viruses must be able to rely on the tools and researchers involved in personalised medicine. Here are the challenges:

Clinical forms, management and outcome: a great heterogeneity

This disease is heterogeneous in its clinical presentation. The vast majority of patients will develop non-severe forms. However, for these ambulatory or early-diagnosed patients, there are three objectives: to decrease the duration of symptoms, to limit the development of a severe form and to decrease the duration of contagiousness. The main issue is to determine which patient will be at greater risk of developing a severe form by going beyond simple demographic characteristics and associated pathologies in order to set up surveillance, or even treatment, adapted to the situation.

Patients with severe forms may be hospitalised at the beginning of the disease during which the viral phase is important or, more frequently, at the inflammatory phase, a week after the onset of the disease. Among these patients, some will have more significant biological inflammatory symptoms than others. Thrombotic events will also affect some patients. Thus, the major challenge in the management of the disease is to evaluate the kinetics of the disease and the risk of progression to more severe forms, using clinical and paraclinical parameters. The objective would be to begin optimal treatment combinations according to the date of onset of the disease. In this way, the management of COVID-19 patients ideally goes beyond a simple “one disease, one treatment” but towards “a disease with a clinic-biological form, a particular kinetics and therefore a particular treatment”.

Sequelae and long-term consequences

The duration of symptoms associated with COVID-19 is highly variable. Some patients complain of their persistence or even the appearance of new symptoms several months after the acute infection. The "post-viral" symptoms, also described in other infectious diseases, appear to be present. In all these situations, the complaints are often polymorphic, associating disorders of superior functions (memory, concentration…), joint pain, intense fatigue, shortness of breath and persistence of other initial symptoms (loss of smell and taste disorders). The management of these patients is complex and is similar to that of rare and systemic diseases.

Epidemiological surveillance and public health measures

The SARS-COV-2 epidemic has shown that massive isolation measures can limit the spread of the virus, with major socio-economic consequences. Ideally, in order to limit the impact of the epidemic as much as possible, we need to determine more specifically which activities to stop, which individuals to isolate and how to track contact. As the crisis is long term, it is therefore necessary to move from "population-based policies" to prevent transmission to "individual-centred" measures, or at least “occupational-centred” measures, meaning to take into account the everyday activities of individuals.

Attempts at individual-centred prevention have been more or less effective depending on the regions where they have been implemented. On the theoretical level, they remain extremely effective. The problem lies in their implementation with the multiple cultural, technical and organisational obstacles.

Thus, the management of SARS-COV-2 pathologies covers most of the issues covered by personalised medicine. Researchers are therefore inspired by the methods used in this context.

Genetics and transcriptomics research

Infectious diseases are the result of the encounter of a pathogenic agent with a living being, defined by its genetic heritage. Although genetic risk factors of patients favouring the appearance of serious forms or recurrences of infectious diseases are known, the vast majority of severe clinical situations cannot be explained by gene mutation or genetic variability. For SARS-COV-2 infection, genetic variability in the interferon gene has been shown to be an aggravating factor. This discovery does not explain all the serious forms, other genes have yet to be discovered but the major challenge remains: the interaction of different variations in the human genome which could explain individual susceptibilities. Research in -omics is therefore essential to the understanding of this pathology.

Research on Meta-data and big data

The use of giant, coordinated databases to answer epidemiological, clinical and impact questions is the great novelty of this epidemic. The World Health Organisation (WHO) has set up a global collection of clinical information and follow-up of patients infected with SARS-COV-2. In France, many medical databases are coordinated, aiming to provide more precise data to explain the evolution of hospitalised patients. It is necessary to go further by developing our biological and genetic data collection and follow-up capabilities.

Therapeutic research: molecule repositioning and translational research

The emergence of a new pathogen, especially when it is a virus, exposes to the absence of etiological therapy. The emergency strategy involves 1) the repositioning of molecules and 2) the implementation of “bed to the bench” researches.

These two points are also characteristic of the individualised management of rare diseases to which is added the notion of emergency in this context. This requires an optimisation of the procedures already implemented in personalised medicine.

In conclusion, the heterogeneity of the clinical forms of this pathology and its consequences may be surprising. In reality, it is only surprising by the number of patients affected, revealing in a caricatured way the great richness of the clinical presentation of infectious diseases. Therefore, this epidemic offers the opportunity to objectify how specific the encounter between an infectious agent and a living being is, and to seek how to go beyond the principles of infectious disease management, a formalised management for a disease, towards an individualised management.