Individuals with Covid-19 show a wide variety of symptoms, ranging from a complete absence of clinical signs to critical conditions such as acute respiratory distress syndrome. However, patients' condition evolves over time, sometimes unexpectedly or even abruptly, which complicates management. In order to better understand this virus and thus better help patients, a cohort of infected patients, hospitalized because of severe symptoms, has been formed. The data from these patients will make it possible to improve knowledge of this disease, particularly concerning its risk factors. For better management of future patients and future epidemics.
Since the beginning of the Covid-19 epidemic, international data, such as those collected in France, show the same trend: about 20% of cases are serious forms requiring hospitalization. In order to improve the management of these patients, it is essential to detail their characteristics as much as possible. This is a major challenge in the face of a new infectious agent such as SARS-CoV-2.
This is precisely the project of the Parisian research team Infection, antimicrobials, modelling, evolution (IAME)*. These researchers formed a large cohort of patients infected with SARS-CoV-2 with several objectives: firstly, to study the clinical presentation of the disease, describing the initial symptoms, their evolution, clinical worsening, as well as the risk factors for complications and mortality.
Nasopharyngeal swabs, obtained at different times during the disease, are also collected to determine the contagiousness of the virus by identifying the period over which it remains significantly present. Regular blood samples will make it possible to measure the immune response and its intensity, as well as the duration of protection conferred by the antibodies produced during the infection. Analyses will be carried out to identify possible genetic susceptibilities to develop a serious form or complications (fatal or not) of the disease. Finally, the effect of treatments administered to patients will be evaluated, whether or not they have been delivered in the context of a clinical trial, in order to better identify the most promising therapeutic approaches.
France Mentré and Cédric Laouénan, statisticians, are coordinating the deployment of the study in French hospitals. They have already been able to federate around a hundred participating departments, spread throughout France. These departments are invited to include all patients hospitalized for Covid-19, whether or not they are part of a clinical trial comparing different treatment approaches. France Mentré, researcher, biostatistician at Inserm, coordinator of the project, explains :
" The idea is to have a record of clinical (severity, fever, pneumonia), radiological and biological developments on all patients on the national territory, to have specific samples to work on the immune response of monoclonal antibodies, possibly to make drugs out of them and also to work with the Vaccine Research Institute on the possibility of developing vaccines. To understand the evolution of the disease. Now that there are a lot of patients, we're also going to work on studying the risk factors, the severity. In the early evolution of the first few days, can we anticipate which patients are going to get worse secondarily or not? We are collecting data in all the national centres in France - and we have currently [11/03/2020] opened 56 centres in France, 56 hospitals with which we work - and then analysing the data in real time. "
" What I'm trying to produce are indeed indicators to help the DGS in the management of these patients, on the one hand, but the other very important aspect of the cohort is that all these biological measurements will be centralized in different centers - in Pasteur, etc. - and that's what I'm trying to produce. - to understand the physiopathologies and immune responses. "
An internationally shared methodology
Setting up an emergency observational cohort is never an easy task, but the team relied on an international consortium to facilitate it: " ISARIC (International Severe Acute Respiratory and Emerging Infection Consortium) is an international network dedicated to severe emerging respiratory infections. It has a standardized evaluation protocol for these diseases which is transposed to the case of Covid-19 several weeks ago. We were, therefore, able to use it quickly for the follow-up of this cohort," explains France Mentré. All the blood samples will be transferred for analysis in reference laboratories, in order to have results of the highest relevance. Thanks to this protocol, " we will have the same evaluation base as the other participating countries, which will eventually allow us to merge all these data. This will provide us with an international cohort with valuable statistical power," she continues.
Patient recruitment is now underway and will continue as long as the epidemic lasts: " In the field, patients willingly accept to participate in the study, they understand the need for such work". adds the statistician. The duration of participation, from the inclusion visit to the last visit, will be 6 months. But the conclusions of certain analyses will be known as they are carried out, based on the first cases already included. The first results could be obtained within a few weeks...
* unit 1137 Inserm/University Paris 13/University Paris Diderot and CIC-EC 1425 Bichat Hospital, AP-HP
Source: Inserm Paris
The REACTing consortium (REsearch and ACTion targeting emerging infectious diseases), coordinated by Inserm, promotes research against emerging infectious diseases. In mid-March, this consortium selected 20 scientific initiatives aimed at improving knowledge and the fight against Covid-19. The project described in this article is one of them.