Six new research projects concerning Covid-19

On April 10, 2020, ANR announced the funding of 86 projects concerning Covid-19. Six are associated with ENS de Lyon laboratories. The SARS-CoV-2 infection is a global emergency for human health. The interferon response is the body’s first barrier to defending viral infections. This host response is initiated by the recognition of viral elements by receptor and leads to the production of molecules, including interferon, that alert surrounding cells. This response then directly inhibits viral spread or enables the gathering of immune cells at the site of infection. For example, interferon is one of the current therapeutic treatments for patients with Covid-19. We therefore need to know the mechanisms of regulation of this interferon response during the infection with SARS-CoV-2, the cells that produce interferon, its temporal decoders and how SARS-CoV-2 could thwart this host response. This ANR-supported project aims to address these issues.

Coordination: Marlène Dreux, Inserm Research Fellow at the International Centre for Infectious Disease Research (Inserm / CNRS / Lyon 1 / ENS Lyon, associated with HCL)

Social distance and changing social preferences in times of an acute health crisis.

The COVID-19 pandemic has led to the implementation of strict measures to limit contagion. They significantly reduce social interactions in the population. This project examines whether forced confinement, social isolation and fear of contagion affect the ability of individuals to care for others, their propensity to trust them, and their greater or lesser leniency towards people who do not respect the healthcare measures. Two hypotheses are tested: the development of a sense of solidarity and common destiny, possibly reinforced by social media; or a more selfish withdrawal, with a distrust of others. The research team set up an online behavioral economics experiment for three months in mid-March (when the French government announced the lockdown measures) until mid-June. 350 volunteers from GATE-Lab (Lyon, France) are participating in this study. Every week, the same volunteers make in-house decisions to measure the development of social preferences, trust and social norms. The results could lead to recommendations for when lockdown is lifted. In particular, if the study highlights a sharp decline in confidence and pro-sociality, it will be important to implement measures to restore greater pro-sociality and trust among citizens.

Coordination: Marie Claire Villeval, CNRS research director of the Lyon - St-Étienne Economic Analysis and Theory Group (GATE, CNRS / Univ. Lyon 1, Lyon 2 and Jean Monnet / ENS de Lyon)

For a funeral solution to the pandemic and bereavement.

The Covid-19 pandemic means that we are facing an unprecedented health and social crisis. It has disrupted the funeral system, especially in terms of timing. Unlike disaster-related or epidemic-related mortality crises, all deaths in a territory have been affected by lockdown, not just deaths attributable to the virus. In order not to lose valuable sources, it is necessary to document, as quickly as possible, the facilities implemented by funeral professionals and the services of cemeteries and crematoriums, according to constraints related to the management of the pandemic. It is also a question of assessing the impact (material and psychological) of these facilities on the bereaved, and whether they have been able to develop resources to deal with them. This research will take place in three countries: France, Italy and Switzerland.

Coordination: Gaëlle Clavandier, Senior Lecturer at Jean Monnet University in Saint-Etienne at the Max Weber Centre (CWM, CNRS / Lyon 2 / UJM / ENS de Lyon)

Stopping coronaviruses getting into cells.

The scale of the health crisis, caused by the Covid-19 pandemic, calls for the rapid implementation of new preventive and therapeutic approaches. This project aims at interpreting current research results from the project-carrier team, particularly those targeting the measles and Nipah viruses, into the development of new SARS-CoV-2 entry inhibitors in target cells. The strategy is based on inhibiting viral entry, using specific peptides of the viral fusion protein, viral envelope glycoprotein. The project is expected to lead to the identification of a new class of peptide fusion inhibitors targeting endosomes (cell sub-segments), with high antiviral activity and broad spectrum, against several coronaviruses. Their chemistry and solubility will be optimized for pharmacological application. The results of this project will initiate the critical implementation of a new prophylactic and therapeutic strategy against COVID-19 and thus open up new perspectives to prevent and treat this highly infectious disease. The successful development of these fusion inhibitors for human use will enable the development of a technology platform adapted not only to SARS-CoV-2, but also to other coronaviruses that may emerge in the future.

Coordination: Branka Horvat, Inserm Research Director at the International Centre for Infectious Disease Research (Inserm / CNRS / Lyon1 / ENS de Lyon, associated with HCL)

For the evaluation and improvement of measures taken against the virus.

The COVID-19 epidemic has had devastating consequences among residents of nursing homes (known as EHPAD in French) and the same recommendations given to the general public may not be appropriate for these dependent, elderly people who often have pre-existing medical conditions. The aim is to set up a simulation platform to evaluate and improve control measures against the dissemination of COVID-19 in nursing homes. The modelling will include a step estimating transition rates between compartments based on the observed data and a simulation step to quantify the impact of different scenarios on the epidemic. The model will consider 4 populations: residents, staff, physicians and visitors, and the following sections: susceptible to infection, infected in incubation, contagious without symptoms, contagious with symptoms, hospitalized, cured and dead. At the simulation stage, the model will quantify the impact on the epidemic of changes in transition rates due to different control measures, changes in the contact matrix between individuals, and the prevalence of infection among staff and visitors.

Coordination: Philippe Vanhems, professor and hospital practitioner of the Université Claude Bernard Lyon 1, member of the International Centre for Research in Infectious Diseases (Inserm / CNRS / Lyon1 / ENS de Lyon) and head of the Hygiene, Epidemiology, Infectio-vigilance and Prevention department (HCL).
Partners: Biostatistics and Bioinformatics Department (HCL); Institute of Aging (HCL); EpiGreen and EPIMOD.

For faster and cheaper screenings.

The diagnosis and follow-up of serious SARS-CoV-2 infections is based primarily on the identification of a component of the virus in nasopharyngeal or bronchopulmonary samples. This test is also important for screening health care workers in contact with patients or at-risk populations such as the elderly. It will also be very useful during the phase of lifting lockdown restrictions to identify infected people who need to isolate, in addition to serological tests. In this context, a large-scale screening test is required. The current protocol is based on a viral genome amplification technique used by a limited number of laboratories, lasting 3 to 4 hours, requiring expensive equipment and qualified personnel. As an alternative to PCR, BioSpeedia (a spin-off of Institut Pasteur, Paris France), the GIMAP research team, associated with CIRI (University of Saint-Etienne and Lyon) and the Laboratory of Infectious Agents and Hygiene of the Saint-Etienne University Hospital are collaborating to develop a rapid test of antigenic detection that is non-invasive, easy to use and "cost-effective". After optimization of the device, it will be evaluated by clinical samples from patients infected with COVID-19. This rapid antigenic test could be particularly interesting to identify so-called "super-contaminator" patients with a high viral load that can be used in different health structures or beyond.

Coordination: Thomas Bourlet, Professor of Microbiology and Hospital Practitioner of Jean Monnet University, Director of GIMAP, associate team at the International Centre for Research in Infectious Diseases (CIRI, Inserm / CNRS / Lyon 1 / ENS de Lyon).
Partners: Laboratory of Infectious Agents and Hygiene (SAINT-Etienne Hospital, B. Pozzetto); BioSpeedia (spin-off of the Pasteur Institute, Y. Germani)